The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor predicts time to delivery and mode of birth in patients with suspected preeclampsia- a secondary analysis of the INSPIRE trial.

BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor (sFLT1/PLGF) is a useful biomarker for preeclampsia. Since it is a measure of placental dysfunction, it could also be a predictor of clinical deterioration and fetal tolerance to intrapartum stress. OBJECTIVES: We tested the hypothesis that sFLT1/PLGF ratio predicts time to delivery. Secondary objectives were to examine associations between the sFLT1/PLGF ratio and mode of birth, fetal distress, need for labor induction and birthweight z-score. STUDY DESIGN: Secondary analysis of the INSPIRE trial, a randomized interventional study on prediction of preeclampsia/eclampsia in which women with suspected preeclampsia were recruited and their blood sFLT1/PLGF ratio was assessed. We stratified participants into three groups according to the ratio result: category 1 (sFLT1/PLGF≤38); category 2 (sFLT1/PLGF>38 and <85); and category 3 (sFLT1/PLGF≥85). We modelled time from sFLT1/PLGF determination to delivery using Kaplan-Meier curves and compared the three ratio categories adjusting for gestational age at sFLT1/PLGF determination and trial arm with Cox Regression. The association between ratio category and mode of delivery, induction of labour and fetal distress was assessed using a multivariable logistic regression adjusting for gestational age at sampling and trial arm. The association between birthweight z-score and sFLT1/PLGF ratio was evaluated using multiple linear regression. Subgroup analysis was conducted in women with no preeclampsia and spontaneous onset of labor; women with preeclampsia; and participants in the non-reveal arm. RESULTS: Higher ratio categories were associated with a shorter latency from sFLT1/PLGF determination to delivery (37 vs 13 vs 10 days for ratios categories 1-3 respectively), hazards ratio for category 3 ratio of 5.64 (95%CI 4.06-7.84, p<0.001). A sFLT/PlGF ratio≥85 had specificity of 92.7%(95%CI 89.0-95.1%) and sensitivity of 54.72% (95% CI, 41.3-69.5) for prediction of preeclampsia indicated delivery within 2 weeks. A ratio category 3 was also associated with decreased odds of spontaneous vaginal delivery (OR 0.47, 95%CI 0.25-0.89); an almost six fold increased risk of emergency cesarean section (OR 5.89, 95%CI 3.05-11.21); and a three-fold increased risk for intrapartum fetal distress requiring operative delivery or cesarean section (OR 3.04, 95%CI 1.53-6.05) when compared to patients with ratios≤38. Higher ratio categories were also associated with higher odds of induction of labor when compared to ratios category 1 (category 2, OR 2.20, 95%CI 1.02-4.76; category 3, OR 6.0, 95%CI 2.01-17.93); and lower median birthweight z-score. Within subgroups of women a)without preeclampsia and with spontaneous onset of labor and b)women with preeclampsia, the log ratio was significantly higher in patients requiring intervention for fetal distress or failure to progress compared to those who delivered vaginaly without intervention. In the subset of women with no preeclampsia and spontaneous onset of labour, those who required intervention for fetal distress or failure to progress had a significantly higher log ratio than those who delivered vaginaly without needing intervention. CONCLUSION: The sFLT1/PLGF ratio might be helpful in risk-stratification of patients who present with suspected preeclampsia regarding clinical deterioration, intrapartum fetal distress and mode of birth (including the need for intervention in labour).

The sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction: A historical cohort study.

INTRODUCTION: The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction. MATERIAL AND METHODS: This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week. RESULTS: 125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, ß = -3.001, (-3.713 to -2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); ß = -0.698 (-1.064 to -0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061-19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06). CONCLUSIONS: sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.

Primary biliary cholangitis: a rare diagnosis during pregnancy.

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.

The fetal origins of disease: a prospective cohort study on the association of preeclampsia and childhood obesity.

Cardiovascular diseases are the main cause of mortality worldwide, and childhood excess weight/obesity are strong correlators of accumulated risk in later life. A relationship between maternal preeclampsia and offspring's childhood obesity is recognized, but most studies fail to control for strong confounders. Our goal is to analyze the association between preeclampsia and childhood excess weight/obesity, after accounting for important confounders. We recruited 5133 women with singleton pregnancies during admission for delivery. Sixty-seven pregnancies were complicated by preeclampsia. Maternal and children outcomes were assessed at 10 years of age. We analyzed the association between preeclampsia and childhood excess weight/obesity by fitting a linear regression model (using offspring body mass index (BMI) z-score at 10 years of age) and a logistic regression model (using excess weight/obesity status). We then controlled both models for known confounders, namely maternal prepregnancy BMI, parity, and smoking during pregnancy. At 10 years of age, offspring of preeclamptic mothers had a higher BMI z-score and were more likely classified as overweight/obese, but these differences were not statistically significant. After controlling for maternal prepregnancy BMI, parity, and smoking during pregnancy, there was a high magnitude change in the beta coefficient of preeclampsia in the linear (0.175; -0.014) and the logistic regression models (1.48; 1.23) suggesting that the association between preeclampsia and childhood excess weigh/obesity is significantly confounded by these variables. These confounders also showed a significant association with childhood obesity. This finding suggests that in utero exposure to preeclampsia seems to have less impact in childhood obesity than the previously described confounders.

Alvarez waves in pregnancy: a comprehensive review.

Alvarez waves are local rhythmic contractions of the myometrium with high frequency and low intensity. They can be detected using internal or external tocography and electrohysterography. Some researchers correlate these small contractions with the initiation of labor, since they have been described as a pattern representing the uterine response to prostaglandin production. Other authors either do not validate a causality relation between Alvarez waves and labor or suggest that they have low predictive value for preterm labor. Alvarez waves' research has become a multidisciplinary subject with inputs ranging from medical science, biomedical engineering, and related areas. A comprehensive review is herein conducted to summarize the state of the art regarding Alvarez waves and their role in the initiation of labor, namely in preterm birth. The results show that a large number of studies have analyzed and characterized Alvarez waves without necessarily digging into their relationship with labor. Publications were categorized in three groups: (A) reports about morphology and characterization of Alvarez waves; (B) publications reporting a positive causality relation between Alvarez waves and labor; and (C) publications reporting an absence of causality regarding the previous hypothesis. Studies in group B outnumbered those in group C. A critical analysis is presented.

Uterine contractions clustering based on electrohysterography.

The uterine electromyogram, also named Electrohysterogram (EHG), is a non-invasive technique that has been used for pregnancy and labour monitoring as well as for research work on uterine physiology. This technique is well established in this field. There is however a vast unexplored potential in the EHG that is currently the subject of interdisciplinary research work involving different scientific fields such as medicine, engineering, physics and mathematics. In this paper, an unsupervised clustering method is applied to a previously obtained set of frequency spectral representations of the respective EHG signal contractions that were previously automatically detected and delineated. An innovative approach using the complete spectrum projection is described, rather than a set of relevant points. The feasibility of the method is established despite the concerns of possible computational burden incurred by the processing of the whole spectrum. Given the unsupervised nature of this classification, a validation procedure was performed whereas the obtained clusters were labelled through the correlation with the common knowledge about the most relevant uterine contraction types, as described in the literature. As a result of this study, a spectral description of the Alvarez contractions was obtained where it was possible to breakdown these important events in two different types according to their spectrum. Spectral estimates of Braxton-Hicks contractions were also obtained and associated to one of the clusters. This led to a full spectral characterization of these uterine events.

Prediction of Adverse Pregnancy Outcomes in Women with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease associated with major obstetrical complications such as gestational loss, preterm delivery, fetal growth restriction (FGR) and preeclampsia. Published literature is not consensual regarding the main risk factors for each of these outcomes. Our goal with this study was to determine the most important predictors for each of the main adverse pregnancy outcomes in this population. We conducted a retrospective cohort study of unifetal pregnancies of women with the diagnosis of SLE followed in our unit between January 1994 and December 2016. We excluded elective terminations of pregnancy and cases lost to follow-up and we analyzed 157 pregnancies (128 women). Multiple logistic regression models for the outcomes gestational loss, preterm delivery, fetal growth restriction, and preeclampsia were built. Two-sided p-values of < 0.05 were used to determine statistical significance, and two-sided confidence intervals of 95% are reported. In our cohort, the main risk factors for gestational loss were maternal age and the presence of antiphospholipid antibodies. Lupic nephritis was predictive of a preterm delivery and preeclampsia. Renal involvement and lupus flares during pregnancy were risk factors for FGR. Overall, the main risk factor for an adverse pregnancy outcome were lupus flares during pregnancy. Despite optimal pregnancy monitoring, women with SLE are still at risk for adverse pregnancy outcomes. Risk stratification for each of these outcomes is crucial for an effective counselling and tailored monitoring.