Objectives First, to investigate the additive value of second‐trimester placental growth factor (PlGF) for the prediction of a small‐for‐gestational‐age (SGA) neonate. Second, to examine second‐trimester contingent screening strategies. Methods This was a prospective observational study in women with singleton pregnancy undergoing routine ultrasound examination at 19–24 weeks' gestation. We used the competing‐risks model for prediction of SGA. The parameters for the prior model and the likelihoods for estimated fetal weight (EFW) and uterine artery pulsatility index (UtA‐PI) were those presented in previous studies. A folded‐plane regression model was fitted in the dataset of this study to describe the likelihood of PlGF. We compared the prediction of screening by maternal risk factors against the prediction provided by a combination of maternal risk factors, EFW, UtA‐PI and PlGF. We also examined the additive value of PlGF in a policy that uses maternal risk factors, EFW and UtA‐PI. Results The study population included 40 241 singleton pregnancies. Overall, the prediction of SGA improved with increasing degree of prematurity, with increasing severity of smallness and in the presence of coexisting pre‐eclampsia. The combination of maternal risk factors, EFW, UtA‐PI and PlGF improved significantly the prediction provided by maternal risk factors alone for all the examined cut‐offs of birth weight and gestational age at delivery. Screening by a combination of maternal risk factors and serum PlGF improved the prediction of SGA when compared to screening by maternal risk factors alone. However, the incremental improvement in prediction was decreased when PlGF was added to screening by a combination of maternal risk factors, EFW and UtA‐PI. If first‐line screening for a SGA neonate with birth weight < 10th percentile delivered at < 37 weeks' gestation was by maternal risk factors and EFW, the same detection rate of 90%, at an overall false‐positive rate (FPR) of 50%, as that achieved by screening with maternal risk factors, EFW, UtA‐PI and PlGF in the whole population can be achieved by reserving measurements of UtA‐PI and PlGF for only 80% of the population. Similarly, in screening for a SGA neonate with birth weight < 10th percentile delivered at < 30 weeks, the same detection rate of 90%, at an overall FPR of 14%, as that achieved by screening with maternal risk factors, EFW, UtA‐PI and PlGF in the whole population can be achieved by reserving measurements of UtA‐PI and PlGF for only 70% of the population. The additive value of PlGF in reducing the FPR to about 10% with a simultaneous detection rate of 90% for a SGA neonate with birth weight < 3rd percentile born < 30 weeks, is gained by measuring PlGF in only 50% of the population when first‐line screening is by maternal factors, EFW and UtA‐PI. Conclusions The combination of maternal risk factors, EFW, UtA‐PI and PlGF provides effective second‐trimester prediction of SGA. Serum PlGF is useful for predicting a SGA neonate with birth weight < 3rd percenti...
Breast cancer is known as one of the most commonly occurring cancer which can be diagnosed in women. The number of new cases of breast cancer in female patients, both in early stages and in advanced stages, has slowly, but continuously increased in the last decades. Immunotherapy has been used in recent years in the treatment of many types of cancer, due to its reduced adverse reactions and a considerable tolerance when administrated compared to currently used therapies such as chemotherapy, radiation and surgery (1). GcMAF is a protein-derived macrophage-activating factor, a new and unapproved medication that has shown promising results in treating breast cancer (2). This review aims to summarize the studies and case reports presenting the GcMAF experience in breast cancer therapy.
There is consistent evidence that many of the pregnancy complications that occur late in the second and third trimester can be predicted from an integrated 11–13 weeks visit, where a maternal and fetal assessment are comprehensively performed. The traditional aims of the 11–13 weeks visit have been: establishing fetal viability, chorionicity and dating of the pregnancy, and performing the combined screening test for common chromosomal abnormalities. Recent studies have shown that the first trimester provides important information that may help to predict pregnancy complications, such as preeclampsia and fetal growth restriction, stillbirth, preterm birth, gestational diabetes mellitus and placenta accreta spectrum disorder. The aim of this manuscript is to review the methods available to identify pregnancies at risk for adverse outcomes after screening at 11–13 weeks. Effective screening in the first trimester improves pregnancy outcomes by allowing specific interventions such as administering aspirin and directing patients to specialist clinics for regular monitoring.
Objective To explore the possibility of carrying out routine screening for pre‐eclampsia (PE) with delivery at < 28, < 32, < 36 weeks' gestation by maternal factors, uterine artery pulsatility index (UtA‐PI) and mean arterial pressure (MAP) in all pregnancies and reserving measurements of placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) for only a subgroup of the population. Methods This was a prospective observational study in two UK maternity hospitals involving women with singleton pregnancy attending for routine assessment at 19–24 weeks' gestation. The improvement in performance of screening for PE, at fixed risk cut‐offs, by the addition of serum PlGF and sFlt‐1 to screening by maternal factors, UtA‐PI and MAP, was estimated. We examined a policy of contingent screening in which biochemical testing was reserved for only a subgroup of the population. The main outcome measures were the additional contribution of PlGF and sFlt‐1 to the performance of screening for PE and the proportion of the population requiring measurement of PlGF and sFlt‐1 for maximum performance of screening. Results The study population included 37 886 singleton pregnancies. At each risk cut‐off, the highest detection rates for delivery with PE and the lowest screen‐positive rates were achieved in screening with maternal factors, UtA‐PI, MAP, PlGF and sFlt‐1. The maximum performance by such screening was also achieved by contingent screening in which PlGF and sFlt‐1 were measured in only about 40% of the population. Conclusion The performance of screening for PE by a combination of maternal factors, UtA‐PI and MAP is improved by measurement of PlGF and sFlt‐1 in about 40% of the population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Small for gestational age (SGA) fetuses/neonates are characterized by the increased risk for adverse outcomes that can be reduced if the condition is identified antenatally. We have recently developed a new approach in SGA prediction that considers SGA a spectrum condition that is reflected in two dimensions: gestational age at delivery and Z score in birth weight for gestational age. The new method has a better predictive ability than the traditionally used risk-scoring systems and logistic regression models. In this prospective study in 40241 singleton pregnancies, at 19–24 weeks’ gestation, we examined the potential value of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and the ratio of sFlt-1 to the angiogenic placental growth factor (PlGF) in the prediction of SGA. We found that first, sFlt-1 did not improve the performance of screening by maternal risk factors, and second, the ratio of sFlt-1/PlGF had a worse performance than PlGF alone in the prediction of SGA. Consequently, second trimester sFlt-1 and sFlt-1/PlGF are not useful in screening for SGA.
Pregnancy complications such as gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) are frequent and influence not only fetal outcomes but also the maternal cardiac function. GDM and HDP may act as a proxy for increased metabolic and cardiovascular risk later in life. Speckle tracking echocardiography (STE) is a relatively new imaging technique that provides more sensitive assessment than conventional echocardiography of the maternal cardiac function. Recent research suggests that STE can be used during pregnancy and postpartum as a useful method of early detection of subclinical maternal cardiac changes related to pregnancy complications, such as GDM and HDP, and as an indicator for future maternal cardiovascular disorders. The aim of this review was to underline the current value of STE in the follow-up protocol of high-risk pregnant women, as a mean for pre- and postpartum monitoring. A review of the literature was conducted in the PubMed database to select relevant articles regarding the association of STE changes and HDP or GDM in the prenatal and postpartum maternal evaluations. Both GDM and HDP are associated with subtle myocardial changes in shape, size and function; these preclinical cardiac changes, often missed by conventional evaluation, can be detected using STE. Left ventricular global circumferential strain might be an important predictor of maternal cardiovascular disorders and might help to define a high-risk group that requires regular monitoring later in life and timely intervention.
An allantoic cyst is a rare malformation with a frequency of 3 in 1,000,000 that may be seen antenatally by ultrasound assessment when the connection between the cloaca (future bladder) and the allantois fails to regress. A patent urachus that presents as a cyst (allantoic) is usually considered not to be associated with chromosomal abnormalities, but if it is not repaired after birth this leads to complications such as urinary tract infections and stone formation. We present a case of a fetus diagnosed with allantoic cyst at the first trimester ultrasound assessment at 12 weeks gestation. The follow up scans showed a decrease in size of the allantoic cyst with no other obvious major defects and, when invasive testing (amniocentesis with microarray analysis) was performed, a rare microdeletion, 1q21.1q21.2 was identified (1.82 Mb deletion).
The placenta is the site of connection between maternal and fetal circulation, and the liaison is established early in pregnancy. A large variety of pregnancy complications such as preterm birth, fetal growth restriction, or pregnancy loss have placental expression and can be accompanied in some cases of acute or chronic identifiable placental inflamatory lesions. Chronic placental inflammatory (CPI) lesions include chronic villitis of unknow etiology (CVUE), chronic intervillositis of unknown etiology, CIUE (also described as chronic histiocytic intervillositis, CHI), and chronic deciduits. Hydroxychloroquine (HCQ) has been prescribed with good results during pregnancy to prevent adverse perinatal outcomes in maternal autoimmune conditions. Its success has paved the way to its use in CPI as CIUE/CHI; however, to date, there are no prospective, informatively designed, controlled studies on its value in these setting. This review aims to explore the potential role of HCQ in CPI of unknown etiology. Ideally, properly designed, probably multicentric studies should be undertaken to fully understand HCQ’s role for prevention of adverse pregnancy outcomes after a chronic placental inflammation.
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