Ischemic Placental Disease Research Articles

Perinatal outcomes are similar in programmed and modified natural frozen embryo transfer cycles

Research QuestionHow do perinatal outcomes differ between programmed and modified natural Frozen Embryo Transfer cycles? DesignWe performed a retrospective cohort study of 839 patients at a university-affiliated fertility practice undergoing single blastocyst FETs between 2014 and 2020. The primary outcome measures were the incidence of ischemic placental disease, small for gestational age, intrauterine growth restriction, preterm delivery, birthweight, and mode of delivery. ResultsWhen comparing programmed cycles to modified natural cycles, there was no increased risk of ischemic placental disease (adjusted risk ratio (aRR): 0.87; 95% confidence interval (CI): 0.64–1.17), IUGR (unadjusted RR: 0.50, 95% CI 0.14–1.77), or preterm delivery (aRR: 1.10, 95% 0.73–1.65), or SGA infants (aRR: 0.69, 95%: CI 0.40–1.19). Patients in the programmed cohort had an increased risk of cesarean delivery (aRR: 1.32, 95% CI: 1.10–1.59). These outcomes were unchanged when limited to patient undergoing their first cycles. ConclusionsThere are no differences in patient and neonatal clinical outcomes between programmed and modified natural FET cycles. The choice of FET protocol should remain a shared decision between patient and provider.

Association of ischemic placental disease in a Southern California Birth Cohort and PM2.5 chemical species and oxidative potential markers

Road traffic is a significant source of particulate matter pollution, whose exposure is a significant risk factor in pregnancy-related health outcomes. The exact mechanisms behind the relationship between traffic-related air pollution (TRAP) exposure and adverse pregnancy outcomes remain unclear. We aim to assess the relationship between exposure to brake and tire wear-associated metals and oxidative potential and ischemic placental disease (IPD). Data were assembled from a final population of 178 women who sought specialized prenatal care at UCLA between 2016 and 2019 in Los Angeles, CA. Modeled first trimester exposures to chemical constituents and oxidative stress potential of PM2.5, black carbon, and PM2.5 mass concentration. Speciated measurements included tracers of brake wear (barium), tire wear (zinc), and oxidative potential markers based on metal concentrations (KM-SUB-ELF ROS) or laboratory assays (DTT loss, OH radical formation). Exposures were modeled by integrating data from filter samples, a low-cost PM2.5 sensor network, and land-use data. We used logistic regression to estimate the associations between air pollution exposures and IPD, adjusting for covariates assessed through medical records and interviews. Scaled to the interquartile range, odds ratios (95% CI) were as follows: barium OR: 1.7 (1.1, 2.7), zinc OR: 1.4 (.86, 2.4), and oxidative potential markers, both modeled as well as measured through DTT loss and OH formation assays (ORs ranging from 1.1-2.0). Point estimates of effect sizes for PM2.5 and black carbon were lower than most measurements (ORs: 1.3-1.4). mass and black carbon. Our findings suggest two key points: (i) metals associated with brake and tire wear, currently unregulated, may play a role in the relationship between TRAP and adverse pregnancy outcomes, and (ii) reducing tailpipe emissions may not be sufficient to protect pregnant women from TRAP.

Early pregnancy imaging predicts ischemic placental disease

IntroductionTo characterize early-gestation changes in placental structure, perfusion, and oxygenation in the context of ischemic placental disease (IPD) as a composite outcome and in individual sub-groups. MethodsIn a single-center prospective cohort study, 199 women were recruited from antenatal clinics between February 2017 and February 2019. Maternal magnetic resonance imaging (MRI) studies of the placenta were temporally conducted at two timepoints: 14–16 weeks gestational age (GA) and 19–24 weeks GA. The pregnancy was monitored via four additional study visits, including at delivery. Placental volume, perfusion, and oxygenation were assessed at both MRI timepoints. The primary outcome was defined as pregnancy complicated by IPD, with group assignment confirmed after delivery. ResultsIn early gestation, mothers with IPD who subsequently developed fetal growth restriction (FGR) and/or delivered small-for gestational age (SGA) infants showed significantly decreased MRI indices of placental volume, perfusion, and oxygenation compared to controls. The prediction of FGR or SGA by multiple logistic regression using placental volume, perfusion, and oxygenation revealed receiver operator characteristic curves with areas under the curve of 0.81 (Positive predictive value (PPV) = 0.84, negative predictive value (NPV) = 0.75) at 14–16 weeks GA and 0.66 (PPV = 0.78, NPV = 0.60) at 19–24 weeks GA. DiscussionMRI indices showing decreased placental volume, perfusion and oxygenation in early pregnancy were associated with subsequent onset of IPD, with the greatest deviation evident in subjects with FGR and/or SGA. These early-gestation MRI changes may be predictive of the subsequent development of FGR and/or SGA.

Risk of postpartum readmission for depression in relation to ischaemic placental disease: a population-based study.

There are limited data on postpartum readmissions for depression in the United States (US). Specifically, the extent to which ischaemic placental disease (IPD) during pregnancy predisposes patients to develop postpartum depression remains poorly understood. We investigated whether IPD is associated with postpartum readmission for new-onset depression in the first year after delivery. In this population-based study, the 2010-2018 Nationwide Readmissions Database was utilised to evaluate rates of postpartum readmission for depression within the calendar year of delivery hospitalisation among patients with and without IPD. IPD was defined as preeclampsia, placental abruption, or small for gestational age (SGA) birth. We expressed associations between IPD and depression readmission based on a confounder-adjusted hazards ratio (HR) with a 95% confidence interval (CI). Of 33.3 million delivery hospitalisations, 3,027,084 (9.1%) had IPD. The total follow-up among those with and without IPD were 17,855,830 and 180,100,532 person-months, respectively, with a median follow-up of 5.8 months for both groups. Rates of depression readmission were 95.7 (n=17,095) and 37.5 (n=67,536) per 100,000 readmissions among patients with and without an IPD, respectively (HR, 2.39; 95% CI, 2.32-2.47); this risk was the highest for preeclampsia with severe features (HR, 3.14; 95% CI, 3.00-3.29). Patients had a greater risk of readmission if they had any two forms of IPD (HR, 3.02; 95% CI, 2.75-3.33), and those with a concurrent diagnosis of preeclampsia and abruption posed the highest risk (HR, 3.23; 95% CI, 2.71-3.86). These findings suggested that patients with IPD are at a substantially increased risk of readmission for depression within a year following delivery. This study underscores the need for increased surveillance, improved detection, and faster treatment of depression in this vulnerable population. This was an unfunded project.

Different clinical presentation of two pregnancy syndromes: Similar pro and antiangiogenic characteristics near delivery: Fetal growth preeclampsia

This research aimed to determine if there was a statistically significant distinction between the serum anti- but also pro-angiogenic chemical ratios among pregnant women having preeclampsia and/or fetal growth limitation, two clinical subgroups of placental ischemia syndrome. We conducted a prospective case-control study that looked at 77 singleton pregnancies and compared them with and without preeclampsia with 77 singleton pregnancies with and without healthy fetuses, matching for gestational age. All pregnant participants in the trial were analyzed to determine the presence or absence of adverse outcomes. Because once in comparison to the control group, the study participants had higher levels of obtainable endoglin dissolution and the ratio of fms-like tyrosine kinase-1 (sFlt-1) to trophoblastic growth factor. Despite the fact that experimental groups received a same quantity of placental growth factor, this was the case (PlGF). sFlt-1 to PlGF ratio as well as the PE without accompanying FGR cohort were the two areas in which the most prominent outliers were discovered. Since preeclamptic persons have the greatest sFlt-1 levels, this factor may be responsible for the development of PE in the mother due to ischemic placental disease.

Correlation between elevated maternal serum alpha-fetoprotein and ischemic placental disease: a retrospective cohort study

ABSTRACT Background To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD). Methods A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women’s Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups. Results The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group. Conclusions Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.

Similar Pro- and Antiangiogenic Profiles Close to Delivery in Different Clinical Presentations of Two Pregnancy Syndromes: Preeclampsia and Fetal Growth Restriction.

The purpose of this study was to evaluate serum levels of anti- and pro-angiogenic substances measured using enzyme-linked immunosorbent assays and their ratios in pregnancies complicated by different clinical subsets of placental ischemic syndrome: preeclampsia and/or fetal growth restriction. A prospective case-control study was performed consisting of 77 singleton pregnancies complicated by preeclampsia, preeclampsia with concurrent fetal growth restriction (FGR), and isolated normotensive FGR pairwise matched by gestational age with healthy pregnancies. The entire study cohort was analyzed with respect to adverse pregnancy outcomes that occurred. In all investigated subgroups, placental growth factor (PlGF) was lower and soluble endoglin (sEng), the soluble fms-like tyrosine kinase-1-sFlt-1/PlGF and sFlt-1*sEng/PlGF ratios were higher than in the control group. The differences were most strongly pronounced in the PE with concurrent FGR group and in the sFlt-1/PlGF ratio. The highest sFlt-1 values in preeclamptic patients suggest that this substance may be responsible for reaching the threshold needed for PE to develop as a maternal manifestation of ischemic placental disease. The FGR is characterized by an elevated maternal sFlt-1/PlGF ratio, which boosts at the moment of indicated delivery due to fetal risk. We concluded that angiogenic imbalance is reflective of placental disease regardless of its clinical manifestation in the mother, and may be used as support for the diagnosis and prognosis of FGR.

Применение Кокарнита у пациенток с ишемической болезнью плаценты в послеродовом периоде

schemic placental disease, which includes such nosological entities as preeclampsia, fetal growth retardation and placental abruption, is commonly the cause of premature labor, which makes it an urgent medical and biological problem. To increase the efficacy of preventive measures, it seems promising to use metabolic therapy, which implies a direct effect on metabolic processes at the tissue and cellular levels. The antioxidant effect of metabolic drugs can reduce the formation of reactive oxygen species and peroxyl radicals in the blood and tissues, and prevent cellular damage. The authors present their experience concerning the use of Cocarnit® metabolic drug, which includes triphosadenine, cocarboxylase, cyanocobalamin and nicotinamide, in complex therapy in the late postpartum period in patients with ischemic placental disease. The use of this drug improves the hemodynamic parameter control, normalizes carbohydrate metabolism, contributes to the rapid restoration of hemoglobin levels in combination with iron preparations, as well as to a softer and faster rehabilitation of female patients in this group, increasing the probability of a favorable outcome in future pregnancy. It should be noted that the preliminary results obtained by the authors require further randomized comparative clinical trials on large samples. KEYWORDS: pregnancy, ischemic placental disease, postpartum period, fetal death, Cocarnit, triphosadenine, cocarboxylase, nicotinamide, cyanocobalamin, metabolic therapy. FOR CITATION: Dobrokhotova Yu.E., Dzhokhadze L.S. Cocarnit in female patients with ischemic placental disease in the postpartum period. Russian Journal of Woman and Child Health. 2023;6(4):385–390 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-10.

Risk of postpartum readmission for depression in patients with ischemic placental disease

There are limited data on postpartum hospitalizations for depression in the United States. Specifically, the extent to which ischemic placental disease (IPD) during pregnancy predisposes patients to develop postpartum depression remains poorly understood. We determined the risk of postpartum readmission for new onset depression in the first year after delivery following a pregnancy complicated by IPD.

Alterations in placental vasodynamics: A window into pathophysiology through sonography of ex vivo perfused placentae

To characterize vasodynamic response in placentae associated with healthy pregnancies and those complicated by placental-mediated disease with elastography. Sonographic elastography is an emerging technology being applied to clinical placental assessment. Administration of vasoactive agents to perfused placentae is a novel strategy to define the role of vascular dynamics in generation of sonographic parameters. Prospective, descriptive cohort study of patients enrolled for post-delivery placental collection with uncomplicated pregnancies and those with ischemic placental disease (IPD; preeclampsia, fetal growth restriction), gestational hypertension (gHTN) or chronic hypertension (cHTN). Following single lobule placental perfusion, shear wave speeds (SWS) obtained via ultrasound elasticity under physiologic conditions and with sequential introduction of vasodilator and vasoconstrictor, then analyzed descriptively and normalized to individual subject level reference conditions. 13 term patients enrolled with 12 placental regions analyzed per perfusion state in triplicate totaling 689 SWS measurements. Mean SWS computed in each perfusion condition across tissue surfaces (Figure 1). Subject level data normalized to physiologic perfusion conditions and the SWS difference between administration of vasoconstrictor and vasodilator assessed (Figure 2). In healthy placentae, there was a small but consistent increase in SWS from vasodilation to vasoconstriction as the tissue became stiffer. In contrast, only the maternal surface in IPD demonstrated greater stiffness and cHTN, gHTN placentae demonstrated a paradoxical response throughout with increased tissue compliance. Direct vasoactive manipulation of the perfused placenta demonstrates subtle stiffening with vasoconstriction in healthy placentae and a variable response across disease states. This may represent a downstream consequence of disease-related vascular injury or a potentially pathogenic upstream atypical vascular response; the later would represent an opportunity for studies predicting placental-mediated disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A Description of the Imaging Innovations for Placental Assessment in Response to Environmental Pollution Study.

The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

Effects of Different Endometrial Preparation Regimens during IVF on Incidence of Ischemic Placental Disease for FET Cycles.

We conducted this retrospective cohort study aiming to compare the different pregnancy outcomes of endometrial preparation regimens on ischemic placental disease in a frozen embryo transfer cycle. The study included a total of 9351 women who had undergone therapy at our single tertiary hospital from January 2015 to July 2020. The women were divided into three groups depending on their endometrial regimens: natural cycle, stimulation cycle, hormone replacement therapy cycle. The data were analyzed after propensity score matching, then we used multiple linear regression to study the relationship between ischemic placental disease and endometrial regimens, adjusted by confounding factors including age, body mass index, and score of propensity score matching. We performed univariate logistic regression, as well as multivariate logistic regression for ischemic placental disease, small for gestational age infant, placental abruption. and pre-eclampsia, respectively, listing the odds ratio and p-values in the table. As a result, risk of ischemic placental disease and small for gestational age infant were detected as higher in stimulation cycles compared to natural cycles before or after adjustment. Hormone replacement therapy cycles conferred a higher risk of pre-eclampsia and preterm delivery compared to natural cycles. No difference was found between stimulation cycles and hormone replacement therapy cycles, regardless of whether they are adjusted or not. In summary, more pharmacological intervention in endometrial preparation was associated with a higher risk of ischemic placental disease related symptoms than natural cycles for endometrial preparation in women undergoing frozen embryo transfer. Our findings supported that minimizing pharmacological interventions during endometrial preparation when conditions permit has positive implications for improving pregnancy outcomes.

Association of Early Beta Human Chorionic Gonadotropin With Ischemic Placental Disease in Singleton Pregnancies After In Vitro Fertilization.

Objectives: To evaluate whether an initial or two-day percent increase in serum beta-human chorionic gonadotropin (βhCG) is associated with ischemic placental disease (IPD) in singleton pregnancies after autologous or donor IVF.Study design: This was a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles at a single academic tertiary hospital and infertility treatment center. We included all patients (≥18 years old) who had a singleton live birth or intrauterine fetal demise (IUFD) resulting from either autologous fresh (n=1,347), autologous frozen (n=454), or donor (n=253) IVF cycles.Main outcome reassures: The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. IPDs included preeclampsia, placental abruption, and small for gestational age (SGA).Results: Neither initial βhCG nor two-day percent increases in βhCG were associated with an increased risk of IPD for any type of IVF cycle. Initial and two-day percent increases in βhCG were significantly higher when comparing frozen with fresh IVF and donor with autologous IVF (all P≤0.01).Conclusions: Among singleton autologous and donor IVF cycles, the initial and two-day percent increase in serum βhCG were not associated with IPD or its components. However, significant βhCG differences existed by cycle type and oocyte source.

Predictive performance of first trimester serum galectin-13/PP-13 in preeclampsia screening: A systematic review and meta-analysis.

Placental protein-13 (PP-13) is a member of the galectin group involved in placental implantation, maternal artery remodeling, and placental inflammatory processes. Its levels are lower in the first trimester for pregnancies later affected by ischemic placental disease, and slowly increase during the second and third trimesters of pregnancy. The aim of the present meta-analysis is to assess the predictive performance of PP-13 in first trimester preeclampsia screening. PubMed, Web of Science, Scopus, Embase, BIOSIS, and Cochrane databases were used to find relevant studies. All prospective and retrospective observational studies that evaluated the accuracy of PP-13 in predicting preeclampsia were assessed. The investigation revealed that the quantitative synthesis was based on 14 studies with a total number of 8,239 women. The pooled sensitivity of PP-13 for the prediction of preeclampsia was 0.53 [95% (confidence interval (CI), 0.08-0.99], and the pooled specificity was 0.83 (95% CI, 0.38-1.29). Further analysis revealed a higher accuracy of PP-13 for the screening of late-onset preeclampsia [pooled sensitivity of 0.58 [95% CI, -0.17-1.33) with a specificity of 0.85 (95% CI, 0.10-1.60)] when compared with early-onset preeclampsia [pooled sensitivity of 0.51 (95% CI, -0.04-1.05) with a specificity of 0.88 (95% CI, 0.33-1.42)]. In conclusion, PP-13 appears to be a promising biomarker for evaluating the risk of developing preeclampsia during the first trimester of pregnancy. As a result, incorporating it into future predictive models is a viable option.

The effect of fetal gender on the biochemical markers of the first-trimester screening.

To determine the effects of fetal gender on the maternal levels of first-trimester screening biochemical markers, such pregnancy-related plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG). In this retrospective study, we assessed 267 cases of singleton pregnancies, who underwent first trimester screening tests and delivered between January 2016 and January 2019 at our hospital. Multiple of median (MoM) levels of PAPP-A and free β-hCG, and the neonatal genders according to the birth records were compared and analyzed. Additionally, patients with small for gestational age (SGA) newborns, preeclampsia, and placental ablation, called ischemic placental diseases, were classified into a separate group and their PAPP-A and free β-hCG MoM values and fetal genders were compared. There was no significant relationship between the mean values of PAPP-A (1.07±0.6) and free β-hCG (1.23±1.14) and the fetal gender (males: 137, 51.3%; females: 130, 48.7%), respectively (p=0.833; p=0.075). In 41 cases (15.4%) with ischemic placental disease, free β-hCG values was significantly higher in the fetal females (19 cases; 46.3%) than males (22 cases; 53.7%), (1.53±1.02 and 0.77±0.53, respectively), (p=0.004). Pregnancy-related plasma protein A and free β-hCG values were not affected by the fetal gender. However, the significant relationship observed between free β-hCG MoM levels and fetal gender in patients with ischemic placental diseases suggests the need for larger studies on this topic.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD. To quantify the contribution of multifoetal gestations to the association between IVF and IPD. We conducted a retrospective cohort study at a tertiary hospital from 1January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non-IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non-IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

Invited Commentary: Intermittent Opioid Use and Ischemic Placental Disease-Clarifying Associations With Adverse Pregnancy Outcomes.

Discomfort and, to a lesser extent, pain are common complaints during pregnancy, and some patients may turn to opioids for pain relief. Esposito et al. (Am J Epidemiol. 2022;191(5):759-768) report associations between intermittent exposure to opioids during pregnancy and the risk of ischemic placental disease-a syndrome that includes preeclampsia, placental abruption, births that are small for gestational age, and preterm delivery. They found that early opioid exposure in pregnancy was associated with a modestly increased risk for abruption, births that are small for gestational age, and preterm delivery, and both early and late exposures were associated with the greatest risk for these outcomes. Surprisingly, preeclampsia was not associated with opioid use. Through quantitative bias analysis, the authors cleverly tackle a number of biases to assess their roles in explaining the associations, including unmeasured confounding, outcome misclassification, and residual confounding; none exerted strong influences on the associations. Although the findings appear fairly robust on the surface, the lack of association between intermittent opioid use and preeclampsia, and important differences in characteristics of patients in the opioid-exposed group compared with the unexposed group, suggest that further study is needed to clarify the relationship between intermittent opioid use, lifestyle factors, and ischemic placental disease risk.

Esposito et al. Respond to "Opioid Use and Ischemic Placental Disease".

Esposito et al. Respond to "Opioid Use and Ischemic Placental Disease".

WS-5. Proposal for a novel classification based on onset of HDP; antenatal onset, labor onset, and postpartum onset

Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown.Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)].We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as < 10th percentile using U.S. growth curves.The cohort included 166 deliveries in the lowest tertile of progesterone (0.2–0.73 ng/ml), 166 deliveries in the middle (0.64–1.05 ng/ml) and 167 deliveries in the highest tertile (1.05–5.6 ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1–2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD.In an IVF population, elevated serum progesterone in the range of 0.64–1.05 ng/mL on the day of hCG administration was associated with a small increased risk of IPD.

Maternal blood count parameters of chronic inflammation by gestational age and their associations with risk of preterm delivery in the Japan Environment and Children\u2019s Study

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), are three reportedly predictive biomarkers that reflect subclinical chronic inflammatory burden. However, how these biomarkers change during pregnancy and its clinical utility among pregnant women have been rarely studied. Among 76,853 singleton pregnancies delivered at 28–41 weeks of gestation that were enrolled in the Japan Environment and Children’s Study, we observed the distribution of maternal NLR, PLR, and LMR values from week 0 to week 36 using spline curves, as well as their predictive values for preterm delivery with and without hypertensive disorders in pregnancy, placental abruption and intrauterine growth restriction (collectively termed ischemic placental disease due to their shared pathological and pathophysiological features) for measurements at 8–11 weeks, 12–17 weeks, and 18–21 weeks. NLR and PLR increased, whereas LMR decreased, with increasing gestation. High LMR and low NLR observed at 18–21 weeks, but not at earlier gestations, were associated with higher risk of preterm delivery with IPD (odds ratio 1.80 [95% CI 1.02, 3.19] per log[LMR]; odds ratio 0.49 [95% CI 0.29, 0.82] per log[NLR]). All parameters were not predictive of preterm delivery without IPD. We provide a robust reference curve for maternal blood count parameters NLR, PLR, and LMR by gestational week.