Changes in cytokine and sequestosome-1 levels during twin pregnancy progression: Association with outcome.

BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions. OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome. STUDY DESIGN: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined. RESULTS: IL-1ß (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1ß concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1ß in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1ß level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05). CONCLUSION: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.

Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhoea.

RESEARCH QUESTION: Women with endometriosis are frequently affected by headache. How many of these have a clear diagnosis of migraine? Are the different forms of migraine related to the phenotypes and/or characteristics of endometriosis? DESIGN: This was a prospective nested case-control study. A consecutive series of 131 women with endometriosis who attended the endometriosis clinic were enrolled and examined for the presence of headache. A headache questionnaire was used to determine the characteristics of the headaches, and the diagnosis of migraine was confirmed by a specialist. The case group included women with endometriosis and a diagnosis of migraine, while the control group included women with only endometriosis. History, symptoms and other comorbidities were collected. A pelvic pain score and associated symptoms were assessed using a visual analogue scale. RESULTS: A diagnosis of migraine was made in 53.4% (70/131) of participants. Pure menstrual migraine was reported by 18.6% (13/70), menstrually related migraine by 45.7% (32/70) and non-menstrual migraine by 35.7% (25/70). Dysmenorrhoea and dysuria were significantly more frequent in patients with endometriosis and migraine than in those without migraine (P = 0.03 and P = 0.01). No difference was found for other variables, including age at diagnosis and duration of endometriosis, endometriosis phenotype, the presence of other autoimmune comorbidities or heavy menstrual bleeding. In most patients with migraine (85.7%) the headache symptoms had started years before the diagnosis of endometriosis. CONCLUSION: The occurrence of headache in many patients with endometriosis is associated with the presence of different forms of migraine, is related to pain symptoms and often precedes the diagnosis of endometriosis.

Universal cervical length screening for preterm birth is not useful after 24 weeks of gestation.

INTRODUCTION: Cervical length measurement using transvaginal sonography at 18+0 -24+0 weeks of gestation is used to identify women at risk of preterm delivery, who may benefit from treatment with progesterone to prevent premature birth. Few and conflicting data exist regarding the predictive value of cervical length measurement performed at later gestational ages. The primary objective of this study was to evaluate the predictive accuracy for spontaneous preterm birth of a single cervical length measurement performed between 24 and 32 weeks of gestation in asymptomatic singleton pregnancies at low risk for spontaneous preterm birth. The secondary objective was to test the predictive accuracy of different cervical length thresholds in the same population. MATERIAL AND METHODS: This was a historical cohort study conducted in a tertiary referral hospital. A total of 2728 asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth were recruited. Of these women, 1548 had cervical length measured at 24+0 -27+6 weeks of gestation and 2191 women at 28+0 -32+0 weeks. In all, 1010 women were present in both gestational age windows. Maternal demographics, medical and obstetrical history, and pregnancy outcome were reviewed. The predictive value of cervical length for spontaneous preterm birth was evaluated through logistic regression analysis. Results were adjusted for confounding factors. RESULTS: Overall, spontaneous preterm birth occurred in 53/2728 women (1.9%). In both the 24+0 -27+6 and 28+0 -32+0 weeks groups, a shorter cervical length was significantly associated with spontaneous preterm birth (p < 0.01), but it had a low predictive value, as shown by the receiver operating characteristics curve analysis (areas under the curve 0.62, 95% CI 0.50-0.74 for the 24+0 -27+6 weeks group, and 0.61, 95% CI 0.52-0.70 in the 28+0 -32+0 weeks group). When the predictive accuracy for preterm delivery of different cervical length cut-offs was evaluated, the sensitivity and positive predictive value were low in both gestational age windows, irrespective of the threshold used. CONCLUSIONS: In asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth, the predictive value of cervical length after 24+0 weeks of gestation is low. Therefore, cervical length screening in these women should be discouraged.

The role of family history of preterm delivery in the individual risk of spontaneous preterm delivery: a case-control study.

PURPOSE: To investigate the role of family history of preterm delivery (PTD) in the individual risk of spontaneous preterm delivery. METHODS: A retrospective case-control study was conducted on 354 patients who delivered between 2018 and 2020. 177 women who delivered preterm were matched with 177 controls who had full-term delivery. A questionnaire was administered to investigate the family history of PTD of both the patient and her partner. Cases and controls were matched for the anamnestic risk factors for PTD. RESULTS: Seventeen of 173 women (9.8%) in the PTD group reported being born preterm, compared to five of 169 women (2.9%) in the control group (p = 0.01), with an odds ratio (OR) of 3.57 (95% confidence interval, CI 1.29-9.92). Women who delivered preterm also reported more frequently having a sibling who was born preterm (12.4% vs. 4.2%, p = 0.01), with an OR of 3.18 (95% CI 1.31-7.7). No association was found between the partner's family history of premature delivery and the patient's risk of preterm delivery in the present pregnancy. CONCLUSIONS: Pregnant patients who were born prematurely or who have siblings born preterm have an increased risk of preterm delivery in their own pregnancies. Assessment of female personal and family history of PTD should be used to identify women at risk of having a PTD in the present pregnancy.

Exploring Plasma-Level Gut Microbiota Mediators and Pro-Inflammatory Markers in Pregnant Women with Short Cervix and Gestational Diabetes Mellitus.

The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal and immunological modifications. Moreover, dysbiosis during pregnancy has been associated with preterm birth, which is influenced by factors such as cervical shortening, infection, inflammation, and oxidative stress. However, dysbiosis also affects the levels of lipopolysaccharide-binding protein (LBP), short-chain fatty acids (SCFAs), and free fatty acids (FFA) in other tissues and the bloodstream. In this study, we investigated the plasmatic levels of some pro-inflammatory cytokines, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), heat shock protein 70 (Hsp70), and microbial markers in pregnant women with a short cervix (≤25 mm) compared to those with normal cervical length (>25 mm). We examined the differences in the concentration of these markers between the two groups, also assessing the impact of gestational diabetes mellitus. Understanding the relationship between GM dysbiosis, inflammatory mediators, and cervical changes during pregnancy may contribute to the identification of potential biomarkers and therapeutic targets for the prevention and management of adverse pregnancy outcomes, including preterm birth.

Antepartum unscarred uterine rupture caused by placenta percreta: a case report and literature review.

The main risk for uterine rupture is the presence of a uterine scar due to prior cesarean delivery or other uterine surgery. However, rupture in an unscarred uterus is extremely rare, and risk factors include multiple gestations, trauma, congenital anomalies, use of uterotonics and placenta accreta spectrum.Placenta accreta spectrum, also known as morbidly adherent placenta, is becoming increasingly common and is associated with significant maternal and neonatal morbidity and mortality.We report a case of unscarred uterine rupture due to placenta percreta in a multiparous woman that required emergency peripartum hysterectomy.

Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study.

OBJECTIVE: To establish pregnancy-specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations. DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. POPULATION: Healthy pregnant women at term admitted to the Obstetrics Department over a period of 1 year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any coexisting condition of increased risk for ICP. METHODS: Both fasting (after 8-14 h of fasting) and postprandial (2 h after meal) TSBA concentrations were measured in 612 women (with 528 fasting samples and 377 postprandial samples) by automated enzymatic spectrophotometric assay. MAIN OUTCOME MEASURES: Fasting and postprandial TSBA concentrations in 612 women. RESULTS: Reference intervals of 4.4-14.1 µmol/L for fasting TSBA and 4.7-20.2 µmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting values, with a median increase of 1.0 µmol/L (p < 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as correlations with fetal sex, parity and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values measured in the winter season (p < 0.01 and 0.02, respectively) CONCLUSIONS: Normal pregnancy is associated with mild hypercholanaemia, and therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limits observed in our healthy pregnant population (14 µmol/L for fasting TSBA and 20 µmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial measurement is essential for the assessment of severity, it is recommended to measure both values rather than use random sampling. TWEETABLE ABSTRACT: Normal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP.

Non-Clinical Variables Influencing Cesarean Section Rate According to Robson Classification.

Background and Objectives: The incidence of cesarean section (CS) has progressively increased worldwide, without any proven benefit to either the mother or the newborn. The aim of this study was to evaluate the association between CS rates and both clinical and non-clinical variables, while applying the Robson classification system. Materials and Methods: This is a retrospective observational study of pregnant women delivering at a tertiary care hospital between 2012 and 2017, either under public or private healthcare. The overall CS rate, and the elective and non-elective CS rate, divided by classes of Robson, were determined. The rate of vaginal deliveries and CSs was compared between the public and private setting. The distribution of incidence of non-elective CSs and their main indications were analyzed between daytime and nighttime. Results: 18,079 patients delivered during the study period: 69.2% delivered vaginally and 30.8% by CS. Robson class 5 was the most frequent (23.4%), followed by class 2B (16.8%). Of the 289 private practice deliveries, 59.2% were CSs. The CS rate was significantly higher in private compared to public practice: 59.2% and 30.4%, respectively (OR 3.32, 95% CI 2.62 ± 4.21). When only considering elective CSs, a statistically significant difference was found in Robson class 5 between private and public practice, with the latter having more CSs (94.2% and 83.8%, respectively (p = 0.046)). The rate of non-elective CS was significantly lower during nighttime than during daytime (17.2% vs. 21.5%, p < 0.01). During daytime, the higher incidence of CS occurred between 4:00 and 4:59 pm, and during nighttime between 9:00 and 9:59 pm. Failed induction was significantly more common as an indication to CS during daytime when compared to nighttime (p = 0.01). Conclusions: This study identified two non-clinical variables that influenced the CS rate: the type of healthcare setting (private vs. public) and the time of the day. We believe that these indications might be related more to the practitioner attitude, rather than objective delivery complications.

TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal.

Safranal, contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. However, the underlying mechanisms for such effects are poorly understood. We explored whether safranal targets the transient receptor potential ankyrin 1 (TRPA1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates TRPA1, but not the TRP vanilloid 1 and 4 channels (TRPV1 and TRPV4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion (DRG) neurons. Genetic deletion or pharmacological blockade of TRPA1 attenuated safranal-evoked release of calcitonin gene-related peptide (CGRP) from rat and mouse dorsal spinal cord, and acute nociception in mice. Safranal contracted rat urinary bladder isolated strips in a TRPA1-dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate (TRPA1 agonist), but not that of capsaicin (TRPV1 agonist) or GSK1016790A (TRPV4 agonist), to evoke currents in DRG neurons, contraction of urinary bladder strips and CGRP release from spinal cord slices in rats, and acute nociception in mice underwent desensitization. As previously shown for other herbal extracts, including petasites or parthenolide, safranal might exert analgesic properties by partial agonism and selective desensitization of the TRPA1 channel.

Reflected hemodynamic waves influence the pattern of Doppler ultrasound waveforms along the umbilical arteries.

The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction or stillbirth. Animal studies have identified reflected pressure waves traveling counter to the direction of blood flow as an important factor in the shape of these waveforms. In the present study, we establish a method to measure reflected waves in the human umbilical artery and assess their influence on blood velocity pulsation. Ninety-five pregnant women were recruited from a general obstetrics clinic between 26 and 37 wk of gestation and examined by Doppler ultrasound. Blood velocity waveforms were recorded for each umbilical artery at three locations along the umbilical cord. With the use of a computational procedure, a pair of forward and reverse propagating waves was identified to explain the variation in observed Doppler ultrasound waveforms along the cord. Among the data sets that met data quality requirements, waveforms in 93 of the 130 arteries examined agreed with the wave reflection model to within 1.5% and showed reflections ranging in magnitude from 3 to 52% of the forward wave amplitude. Strong reflections were associated with large differences in pulsatility between the fetal and placental ends of the cord. As reflections arise from transitions in the biomechanical properties of blood vessels, these observations provide a plausible mechanism for the link between abnormal waveforms and clinically significant placental pathology and could lead to more precise screening methods for detecting pregnancies complicated by placental disease. NEW & NOTEWORTHY The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction. We demonstrate based on a study of 95 pregnant women that the shape of these umbilical artery waveforms is explained by the presence of a reflected pressure wave traveling counter to the direction of blood flow.

Insulin-like growth factor binding protein-1 predicts preterm premature rupture of membranes in twin pregnancies.

PURPOSE: Mechanisms leading to preterm premature rupture of membranes (PPROM) remain incompletely defined. Based on the elevated occurrence of PPROM in twin gestations and recent studies of the involvement of insulin-like growth factor binding protein-1 (IGFBP-1) in the inhibition of collagen production we hypothesized that serum IGFBP-1 levels might be predictive of susceptibility to PPROM in women with twins. METHODS: In this prospective study peripheral blood was obtained from 58 women with twin gestations prior to 20 weeks gestation and sera analyzed by ELISA for concentrations of IGFBP-1. Demographic and clinical outcome data were subsequently obtained and associations between IGFBP-1 and PPROM were analyzed by the Mann-Whitney test and receiver operator curve (ROC) analysis. RESULTS: Eight of our subjects developed PPROM. They did not differ from the other women in demographics, medical history or current pregnancy outcome parameters. However, median IGFBP-1 levels were higher in women who subsequently developed PPROM (59.3 ng/ml) than in the other women (46.6 ng/ml) (p = 0.042). Using a cutoff value of 53.9 ng/ml the circulating IGFBP-1 level predicted development of PPROM with a sensitivity of 74%, specificity of 75%, a negative predictive value of 97% and a positive predictive value of 20%. CONCLUSIONS: Pending validation in larger studies the findings suggest that determination of serum IGFBP-1 levels in women with twin pregnancies may predict the later development of PPROM.

The Relationship between the Fetal Volume-Corrected Renal Artery Pulsatility Index and Amniotic Fluid Volume.

INTRODUCTION: To evaluate if the volume-corrected renal artery pulsatility index (vcRA-PI) is more closely related to the amniotic fluid level than the uncorrected or the gestational age (GA)-adjusted RA-PI. METHODS: RA-PI and kidney volume were measured in low- and high-risk pregnancies at 17-38 weeks. Fetal anomalies associated with nonrenal causes of abnormal amniotic fluid volume were excluded. The vcRA-PI was calculated by dividing the RA-PI by the renal volume. The RA-PI was adjusted for GA, to obtain the GA-adjusted RA-PI. The uncorrected, GA-adjusted, and the vcRA-PI were related to the amniotic fluid level using nonparametric tests and receiver operating characteristic (ROC) curve analyses. RESULTS: 146 examinations from 59 pregnancies were reviewed. Of these, 16 had oligo- and 15 had polyhydramnios. A higher vcRA-PI was associated with oligohydramnios (OR 2.54, 95% CI 1.67-3.86, p < 0.001), while the uncorrected RA-PI and GA-adjusted RA-PI were not able to predict oligohydramnios. ROC curve analysis showed a high predictive accuracy of the vcRA-PI for oligohydramnios (AUC 0.84, 95% CI 0.72-0.94). On the other hand, the uncorrected RA-PI and GA-adjusted RA-PI significantly predicted polyhydramnios (p = 0.04 and 0.02, respectively), while the vcRA-PI did not. CONCLUSION: The vcRA-PI is superior to the uncorrected and the GA-adjusted RA-PI in predicting oligohydramnios.

Impact of bladder filling on uterine artery Doppler variables in the first trimester of pregnancy.

OBJECTIVE: Uterine artery (UtA) Doppler examination is used in the first trimester to assess the risk of developing preeclampsia, with a standardized technique. However, the impact of bladder filling on UtA circulatory impedance in pregnancy has not been previously studied. This study aimed to examine the effect of bladder distension on UtA-pulsatility index (PI) and peak systolic velocity (PSV) in the first trimester of pregnancy. METHODS: The authors conducted a prospective repeated-measure study on pregnant women presenting for first-trimester screening for preeclampsia. Right and left UtA Doppler velocimetry was first measured with a full bladder. Bladder volume was recorded. After the patients had voided their bladder, a repeat Doppler measurement was performed. The UtA PI and PSV were recorded on each side. The Wilcoxon signed-rank test was used to compare UtA variables before and after bladder voiding. RESULTS: The authors enrolled 45 patients. Mean gestational age at exam was 12.1 weeks. When women were studied with full bladder, median UtA-PI was 1.73 (inter-quartile range, [IQR] 1.49, 2.28) on the right and 1.71 (1.46, 2.11) on the left side. After bladder voiding, values were 1.83 (IQR 1.58, 2.20) and 1.78 (1.40, 2.18). The difference was not statistically significant (P = .26 and 0.80). Similarly, no difference was found in UtA-PSV before and after bladder voiding on either side (P = .22 and .70). CONCLUSION: In the first-trimester of pregnancy, bladder distension does not significantly modify uterine artery Doppler variables.

Unique Associations between Insulin-Like Growth Factor Binding Protein-1, Insulin-Like Growth Factor-1 and T Cell Immunoglobulin Mucin 3 in Successful Twin Pregnancies Conceived with Donor Oocytes.

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.

Aortic isthmus shunt dynamics in normal and complicated monochorionic pregnancies.

OBJECTIVE: To study fetal aortic isthmus (AoI) shunt dynamics in monochorionic (MC) twins. METHODS: Normal and complicated MC pregnancies were prospectively enrolled. The relationship of isthmus flow index (IFI) with Doppler parameters of umbilical artery (UA), descending aorta, middle cerebral artery, and ductus venosus and with left and right ventricular cardiac output and stroke volume was studied. RESULTS: The IFI was obtained in 180 examinations from 48 pregnancies (24 twin-twin transfusion syndrome, TTTS; 4 selective intrauterine growth restriction, sIUGR; 12 TTTS + sIUGR; and 8 uncomplicated). Median gestational age was 20.9 weeks. AoI diastolic flow was reversed in three cases. UA pulsatility index (PI) and ductus venosus-PI z-scores were negatively correlated with the IFI (rs -0.40 and -0.26, respectively, p < 0.001). Regression analysis identified only UA-PI as a determinant of the IFI (p < 0.001). The IFI was significantly correlated with left ventricular cardiac output and stroke volume. It did not differ between TTTS donors and recipients. sIUGR fetuses had significantly lower IFI compared with normal-grown counterparts (p < 0.001). CONCLUSION: In MC gestations, AoI shunting is predominantly determined by placental flow resistance, while cerebral impedance and volume status have no impact. In MC twins, the relationship between AoI flow and outcome deserves further study in the setting of sIUGR. © 2017 John Wiley & Sons, Ltd.

Fetoscopic tracheal occlusion for treatment of non-isolated congenital diaphragmatic hernia.

Fetoscopic endotracheal occlusion (FETO) is a prenatal treatment that may increase survival in severe congenital diaphragmatic hernia (CDH). In the USA, FETO is offered for isolated severe left-sided CDH in the context of an FDA-approved feasibility study. FETO in non-isolated cases of severe CDH is only performed with a compassionate use exemption from US regulatory bodies. Anomalies frequently associated with CDH include congenital cystic lesions of the lung and cardiac defects. We describe two cases of non-isolated severe left-sided CDH that underwent prenatal FETO, survived after birth and underwent postnatal surgical repair. The potential benefit of FETO in this setting is discussed. © 2017 John Wiley & Sons, Ltd.

Ability of cervical length to predict spontaneous preterm delivery in twin pregnancies using the receiver-operating characteristic curve analysis and an a priori cut-off value.

In this retrospective study based on cervical length (CL) measurements between 20 and 24 + 6 weeks, we examined the ability of CL to predict spontaneous preterm birth (SPTB) in 222 twin pregnancies using the receiver-operating curve (ROC) analysis and an a priori cut-off. CL predicted SPTB before 34 weeks. Using the ROC the selected cut-off was 37.5 mm. Positive predictive value (PPV) and negative predictive value (NPV) regarding SPTB before 34 weeks for 37.5 mm were 15.7% and 5.3% respectively. Using the 5th percentile, PPV and NPV regarding SPTB before 34 weeks for 24 mm were 41.7% and 91.4%, respectively. The 5th centile of CL measurements should be employed in clinical practice. CL measurement is an adequate screening tool for SPTB since it has a high NPV. Studies on CL measurement and SPTB should explain which methodology they adopted to obtain a cut-off value and the rationale of their choice.

Ductus venosus Doppler in the assessment of fetal cardiovascular health: an updated practical approach.

The ductus venosus has a central role in the distribution of highly oxygenated umbilical venous blood to the heart. Its waveform is related to the pressure-volume changes in the cardiac atria and it is therefore important in the monitoring of any fetal condition that may affect forward cardiac function. The cardiovascular parameters that can influence forward cardiac function include afterload, myocardial performance and preload. Decreased forward flow during atrial systole (a-wave) is the most sensitive and ubiquitous finding when any of these parameters is affected. In contrast, decreased forward velocities during end-systolic relaxation (v-wave) are more specifically related to myocardial performance. The ductus venosus pulsatility index alone does not accurately reflect cardiac function, and in cases of suspected fetal cardiac dysfunction, echocardiography is required to identify the underlying mechanism. The role of ductus venosus Doppler in the assessment of fetal growth restriction, supraventricular tachycardia, fetal hydrops, complicated monochorionic twins and congenital heart disease is discussed with these considerations in mind.

Relationship between first-trimester serum placental protein-13 and maternal characteristics, placental Doppler studies and pregnancy outcome.

OBJECTIVE: To examine potential correlations between maternal serum placental protein-13 (PP-13) and first trimester maternal and placental factors, and to evaluate the association of this marker with adverse pregnancy outcome. METHODS: Serum samples from prospectively enrolled patients between 11 and 13 weeks and 6 days were analyzed for PP-13 using an ELISA assay. The relationships between maternal serum PP-13 levels and gestational age, maternal age, ethnicity, parity, smoking status, body mass index (BMI), mean arterial blood pressure, uterine and umbilical artery Doppler parameters were examined. The association between first-trimester PP-13 levels and subsequent pre-eclampsia and delivery of a small for gestational age (SGA) neonate was also investigated, after excluding patients who received aspirin. RESULTS: In 908 patients, PP-13 levels ranged from 8.0 to 537.5 pg/mL. A significant negative correlation was identified between PP13 and BMI (Spearman rho -0.20, P<0.0001). Smoking significantly decreased PP-13 (P<0.01). No relationship was identified with the other parameters. In a subgroup of 668 low-risk patients who did not receive aspirin, PP-13 levels were not associated with development of pre-eclampsia, SGA or the combination of them. CONCLUSION: First-trimester PP-13 levels are significantly correlated with BMI and smoking. These correlations appear independent of uterine and umbilical artery resistance. In low risk patients, PP-13 levels fail to predict the risk for pre-eclampsia or SGA.