Comparable Gestational Age Research Articles

INDUCTION OF LABOUR WITH SUBLINGUAL MISOPROSTOL COMPARED TO VAGINAL DINOPROSTONE IN TERMS OF NEONATAL OUTCOME IN WOMEN WITH PROLONGED PREGNANCY

Labor induction in postdate pregnancies can impact neonatal outcomes, including Apgar scores and the need for NICU care. Various induction agents, such as sublingual misoprostol and vaginal dinoprostone, offer differing efficacies. This study aims to compare the neonatal outcomes of these two agents to determine the more effective option for labor induction in postdate pregnancies. Objective: To compare neonatal outcomes, specifically Apgar scores <7 at 1 minute and NICU admissions within the first 24 hours, between neonates born to postdate women induced with sublingual misoprostol versus vaginal dinoprostone. Methods: This randomized controlled trial was conducted in the Department of Obstetrics and Gynecology, Unit 1, Holy Family Hospital, Rawalpindi, from January 2024 to July 2024. After Institutional Research Forum approval, 200 women meeting the selection criteria were randomized via the lottery method into two groups. Group I received 25 mcg of sublingual misoprostol every 4 hours up to 4 doses, and Group II received 3 mg vaginal dinoprostone every 6 hours up to 2 doses. Neonatal Apgar scores were recorded at delivery, and NICU admissions were monitored within 24 hours. Data were documented on structured proforma and analyzed using SPSS. Results: The mean maternal age in Group I was 27.17±4.71 years and in Group II 28.33±4.25 years. Both groups had comparable gestational ages (41.60±0.49 vs. 41.68±0.46 weeks) and parity (1.64±0.79 vs. 2.05±0.83). Group I neonates had higher mean Apgar scores at 1 minute (7.25±2.08) compared to Group II (6.62±2.07), with significant group differences (p=0.04). NICU admissions were required in 30% of neonates, with 48.8% needing NICU care, and fewer admissions in Group I (p=0.04). NICU care showed a significant association with maternal age over 28 years (p=0.000) and nulliparous status (p=0.007) but was not significantly different for those under 28 years or multiparous. Conclusion: Sublingual misoprostol demonstrated superior efficacy to vaginal dinoprostone in labor induction for prolonged pregnancies, with improved neonatal outcomes, including higher Apgar scores and fewer NICU admissions. Age and parity influenced outcomes, highlighting sublingual misoprostol as an effective choice for better neonatal health.

A Moving Target: Studying the Effect of Continuous Transcutaneous CO2 Monitoring in ELBW Infants During an Equipoise Shift.

Objectives: To assess whether continuous non-invasive pCO2 monitoring by transcutaneous pCO2 monitor (TCpCO2) among extremely low birth weight (ELBW) premature infants, during the first week of life, will decrease the rate of high-grade intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) or the combined outcome of IVH/PVL and death. Methods: This was a prospective, observational, multicenter study. Due to ethical constraints, allocation was based on TCpCO2 monitor availability. ELBW infants were either monitored by TCpCO2 monitor (Sentec, Therwil, Switzerland) (study group), or recruited to the control group if a TCpCO2 monitor was not available. Results: A total of 132 ELBW infants participated in the study. The size of the study group (106 infants) and the control group (26 infants) differed because monitor availability increased during the study period reflecting change in standard of care. The groups had comparable gestational age and baseline characteristics. No difference was found in the rate of IVH/PVL in the study vs. control groups (10% vs. 4%; p = 0.7, respectively), or in the combined outcome of PVL/IVH and death (16% vs. 15%; p = 1.0, respectively). Conclusions: This study demonstrates the challenges in conducting a prospective controlled trial in a rapidly evolving medical field. While the study began with a clear equipoise, this balance shifted as the care team gained more experience with TCpCO2 monitoring among the study population, despite the absence of new clinical evidence to justify such a shift. Consequently, the small control group limited our ability to draw definitive conclusions regarding the study's objective. However, our findings may increase awareness of continuous non-invasive pCO2 monitoring in extremely premature infants.

Differential postnatal cardiovascular course of donor-recipient twins and associated pathophysiology-a cohort study.

Fetal echocardiography in twin-to-twin transfusion pregnancies treated with photocoagulation noted impaired cardiac function. Systematic information about cardiac structure or function and arterial distensibility after birth is not available. This study evaluated cardiovascular function and arterial dynamic properties in survivors of twin-to-twin transfusion syndrome (TTTS). Eleven pairs of donor-recipient twins were compared with each other and with 20 singletons of comparable gestational age. The twin cohort was born at 31.5 ± 2 wk gestational age; birthweights of donors-recipients were comparable (donors: 1,358 ± 421 g vs. recipients: 1,617 ± 460 g, P = 0.2). Significant intertwin differences were noted for cardiac function parameters. Recipients had greater septal thickness (donors: 2.3 ± 0.15 vs. recipients: 2.7 ± 0.36 mm, P = 0.01) and globularity [lower sphericity index (donors: 1.76 ± 0.1 vs. recipients: 1.62 ± 0.12, P = 0.009)]. They also had lower cardiac function [tricuspid annular plane systolic excursion (donors: 4.6 ± 0.5 vs. recipients: 4.1 ± 0.4 mm, P = 0.02) and right ventricular fractional area change (donors: 30 ± 1 vs. recipients: 27.7 ± 1.3%, P = 0.0001)]. Compared with singletons, differences were statistically more significant for recipients. Arterial distensibility however was more affected in donors [higher arterial wall stiffness index (donors: 2.5 ± 0.2 vs. recipients: 2.2 ± 0.2, P = 0.008) and lower pulsatile diameter (donors: 51 ± 5 vs. recipients: 63 ± 10 µm, P < 0.0001)]. Compared with singletons, the differences were statistically more significant for donors. Evaluation in the neonatal period noted that cardiac function and arterial distensibility are affected in TTTS twins. These cohorts will benefit from close postnatal follow-up for the evolution of cardiac and arterial impairments.NEW & NOTEWORTHY Evaluation for fetuses with twin-to-twin transfusion syndrome noted impaired cardiac function in recipients. Systematic data after birth are lacking. We noted greater ventricular dilatation, globularity, and hypertrophied interventricular septum in the recipient. Right ventricular contractility was reduced; differences between recipients-singletons had greater statistical significance compared with donors-singletons. The aorta had greater stiffness and lower distensibility in donors compared with recipients; the differences for arterial indices were statistically more significant with donors-singletons.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study

ObjectivesTo compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks’ gestation. MethodsMRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks’ gestation. ResultsDatasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). ConclusionThese findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

Changes in neonatal morbidity, neonatal care practices, and length of hospital stay of surviving infants born very preterm in the Netherlands in the 1980s and in the 2000s: a comparison analysis with identical characteristics definitions

BackgroundThis study evaluates changes in the neonatal morbidity, the neonatal care practices, and the length of hospital stay of surviving very preterm (VP) infants born in the Netherlands in the 1980s and in the 2000s; a period over which historical improvements were introduced into neonatal care. We, herein, also study whether these changes in neonatal morbidity, neonatal care practices and length of hospital stay are associated with sociodemographic, prenatal, and infant characteristics.MethodsTwo community-based cohorts from 1983 (POPS) and 2002−03 (LOLLIPOP) have provided the perinatal data for our study. The analysis enrolled 1,228 participants born VP (before the 32nd week of gestation) and surviving to 2 years of age without any severe congenital malformation. A rigorous harmonisation protocol ensured a precise comparison of the cohorts by using identical definitions of the perinatal characteristics.ResultsIn 2003, mothers were older when giving birth, had higher multiple birth rates, and significantly more parents had received higher education. In 2003, less VP infants had severe intraventricular haemorrhage and sepsis and relatively more received continuous positive airway pressure, mechanical ventilation and caffeine therapy than in 1983. Antenatal corticosteroids and surfactant therapy were provided only in 2003. The length of the stay in the neonatal intensive care unit and in hospital had decreased in 2003 by 22 and 11 days, respectively. Differences persisted after adjustment for sociodemographic, prenatal, and infant characteristics.ConclusionsNeonatal morbidities of the surviving VP infants in this study have not increased, and exhibit improvements for various characteristics in two cohorts born 20 years apart with comparable gestational age and birth weight. Our data suggest that the improvements found are associated with more advanced therapeutic approaches and new national protocols in place, and less so with sociodemographic changes. This analysis provides a basis for further comparative analyses of the health and the development of VP children, particularly with regard to long-term outcomes.

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction

BackgroundFetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. AimEchocardiographic assessment of heart function in FGR neonates first three days after birth. Study designProspective observational study. SubjectsFGR- and non-FGR neonates. Outcome measuresM-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e′ of the atrioventricular plane day one, two and three after birth. ResultsCompared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e′ (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e′ (15 (7) %, p = 0.049), right a′ (18 (6) %, p = 0.001), left E/e′ (25 (10) %, p = 0.015) and right E/e′ (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. ConclusionsFGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.

Reduced Endothelial Progenitor Cells: A Possible Biomarker for Idiopathic Fetal Growth Restriction in Human Pregnancies.

Circulating endothelial progenitor cells (EPCs) may be necessary throughout pregnancy by ensuring proper placentation and embryonic growth. The lack of standardized EPC quantification techniques has prevented conclusive proof of an increase in EPC during pregnancy. The purpose of this study was to determine whether EPC levels change for healthy and idiopathic fetal growth restriction (FGR) pregnancies. The study population consisted of 48 healthy pregnant females with no previous history of IUGR (10 in the first trimester, 15 in the second, and 23 in the third), 48 women with pregnancy complicated by idiopathic FGR, and 15 non-pregnant women. By using flow cytometry, EPCs in maternal blood were recognized as CD45dim/CD34/KDR cells. ELISA was used to measure plasmatic cytokines. We ascertained a progressive rise in EPCs in healthy pregnancies that was apparent in the first but more pronounced in the third trimester. At comparable gestational ages, FGR-complicated pregnancies had impaired EPC growth. Placental growth factor and stromal-derived factor-1 levels in the blood were significantly lower in FGR than in healthy pregnancies, which may have contributed to the degradation of the EPCs. The count in EPCs might hold considerable promise toward developing a peculiar authentication marker for observing pregnancies, and could be the focus of cutting-edge tactics for the prognosis and treatment of FGR pregnancies.

Sex-Specific Differences in Congenital Diaphragmatic Hernia Mortality

To compare disease severity and mortality differences between female and male patients with congenital diaphragmatic hernia (CDH). We queried the CDH Study Group (CDHSG) database for CDH neonates managed between 2007 and 2018. Female and males were compared in statistical analyses using t tests, χ² tests, and Cox regression, as appropriate (P≤.05). There were 7288 CDH patients, of which 3048 (41.8%) were female. Females weighed less on average at birth than males (2.84kg vs 2.97kg, P<.001) despite comparable gestational age. Females had similar rates of extracorporeal life support (ECLS) utilization (27.8% vs 27.3%, P=.65). Although both cohorts had equivalent defect size and rates of patch repair, female patients had increased rates of intrathoracic liver herniation (49.2% vs 45.9%, P=.01) and pulmonary hypertension (PH) (86.6% vs 81.1%, P<.001). Females had lower survival rates at 30-days (77.3% vs 80.1%, P=.003) and overall lower survival to discharge (70.2% vs 74.2%, P<.001). Subgroup analysis revealed that increased mortality was significant among those who underwent repair but were never supported on ECLS (P=.005). On Cox regression analysis, female sex was independently associated with mortality (adjusted hazard ratio 1.32, P=.02). After controlling for the established prenatal and postnatal predictors of mortality, female sex remains independently associated with a higher risk of mortality in CDH. Further study into the underlying causes for sex-specific disparities in CDH outcomes is warranted.

Right ventricular systolic function and associated anatomic risk factors in fetuses with transposition of the great arteries: Evaluation by velocity vector imaging.

The aim of this study was to evaluate right ventricular (RV) systolic function in fetuses with transposition of the great arteries (TGA) using velocity vector imaging (VVI) and to investigate the impact of different factors on RV systolic function in TGA fetuses. This was a retrospective cross-sectional study of fetuses referred to our tertiary center between 2015 and 2019. Maternal and fetal baseline characteristics and conventional echocardiographic and myocardial deformation indices were collected in fetuses with TGA at 20-28 weeks' gestation, which were compared with normal fetuses with comparable gestational age (GA). RV deformational parameters including global and regional longitudinal peak systolic strain, strain rate, and velocity were measured using off-line speckle tracking analysis. The univariate and multivariate linear regression analyses were established to evaluate the independent risk factors for RV global longitudinal systolic strain (RVGLSs) and strain rate (RVGLSRs). In total, 78 fetuses with TGA [including 49 fetuses with complete transposition of the great arteries (d-TGA) and 29 fetuses with Taussig-Bing anomaly (TBA)] and 49 normal fetuses were included. Compared with normal controls, global and most regional RV longitudinal systolic peak velocity, strain, and strain rate were lower in d-TGA and TBA fetuses (P < 0.05). Compared with normal controls, global and most regional RV longitudinal systolic strain was lower in d-TGA fetuses without pulmonary stenosis (PS) and ventricular septal defect (VSD), while RVGLSs and RVGLSRs were lower in TBA fetuses without PS. The VSD was an independent determinant of RVGLSRs (P = 0.024) in the d-TGA group. Additionally, PS was an independent determinant of RVGLSs and RVGLSRs (P = 0.012, P = 0.027) in the TBA group. Early impairment of RV systolic function has already occurred in TGA fetuses during the 2nd trimester of pregnancy. PS, VSD, and foramen ovale (FO) were independent risk factors for decreased RV function.

Magnetic Resonance Imaging Angiography of Physiological and Pathological Pregnancy Placentas Ex Vivo: Protocol for a Prospective Pilot Study.

BackgroundPreeclampsia (PE) and intrauterine growth restriction (IUGR) are 2 major pregnancy complications due to abnormal placental vasculogenesis. Data on whole fetoplacental vasculature are still missing; hence, these pathologies are not well understood. Ex vivo magnetic resonance imaging (MRI) angiography has been developed to characterize the human placental vasculature by injecting a contrast agent within the umbilical cord.ObjectiveThe primary objective of this study is to compare the placental vascular architecture between normal and pathological pregnancies. This study’s secondary objectives are to (1) compare texture features on MRI between groups (normal and pathological), (2) quantitatively compare the vascular architecture between both pathological groups (pathological IUGR, and pathological PE), (3) evaluate the quality of the histological examination in injected placentas, and (4) compare vascularization indices to histological characteristics.MethodsThis is a prospective controlled study. We expect to include 100 placentas: 40 from normal pregnancies and 60 from pathological pregnancies (30 for IUGR and 30 for PE). Ex vivo MR image acquisition will be performed shortly after delivery and with preparation by injection of a contrast agent in the umbilical cord. The vascular architecture will be quantitatively described by vascularization indices measured from ex vivo MRI angiography data. Comparisons of vascularization indices and texture features in accordance with the group and within comparable gestational age will be also performed. After MR image acquisition, placental histopathological analysis will be performed.ResultsThe enrollment of women began in November 2019. In view of the recruitment capacity of our institution and the availability of the MRI, recruitment should be completed by March 2022. As of November 2021, we enrolled 70% of the intended study population.ConclusionsThis study protocol aims to provide information about the fetal side of placental vascular architecture in normal and pathological placenta through MRI.Trial RegistrationClinicaltrials.gov NCT04389099; https://clinicaltrials.gov/ct2/show/NCT04389099International Registered Report Identifier (IRRID)DERR1-10.2196/35051

Late selective termination and the occurrence of placental-related pregnancy complications: A case control study.

Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls. A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups. Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N=43, 20-27.6 weeks); 2) 3rd trimester (N=47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P=0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P<0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons. Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons.

Double diapering facilitates hip maturation in newborns

Double diapering may help to maintain a baby's hips in flexion and abduction posture, but the efficacy in facilitating hip maturation has never been verified. We investigated whether double diapering results in greater improvement of the alpha angle in newborn babies. This prospective study enrolled newborns with Graf type IIa immature hips and assigned them to the double-diaper or single-diaper group by the day of birth in a week. Parents were instructed on proper hip positioning, except for diapering. Change in the alpha angle from newborn to 1 month after birth, rate of improvement to bilateral Graf type I hips in 1 month, and number of ultrasound examinations and orthopaedic clinic visits in the first year were compared between the two groups. Seventy newborns with 102 type IIa hips were included from January to December 2017. They were allocated to the double-diaper group (n=33) and single-diaper group (n=37). With a comparable sex ratio, gestational age, and newborn alpha angle, the double-diaper group had a greater increase of alpha angles in 1 month than the single-diaper group (+7.9° vs. +5.2°, t-test, p=0.011). Twenty-eight babies in the double-diaper group (84.8%) and 20 babies in the single-diaper group (54.1%) improved to having bilateral Graf type I hips (chi-square test, p=0.006). Under the same clinical management pathway, subsequent clinical visits and hip ultrasounds before 1 year were significantly reduced in the double-diaper group. Double diapering enhances hip maturation and reduces clinical costs in newborns with physiological immature hips, but the therapeutic role for hip dysplasia requires further study.

Maternal Serum Creatine Kinase and Single Serum Progesterone Measurement as Predictors of Ectopic Pregnancy

Objective: To evaluate the role of serum creatine kinase (CK) and progesterone (p) in the prediction of ectopic pregnancy (E.P). Patients and methods: A prospective study was carried out on 60 pregnant women of comparable gestational age and they were divided into 3 groups: Group A: 20 patients with confirmed E.P. Group B: 20 patients with missed or spontaneous miscarriage. Group C: 20 women with normal intrauterine pregnancy (IUP). The following laboratory measurements were performed for the studied groups: 1- Test for serum CK level for all groups. 2- Test for serum progesterone for all groups. 3- Histopathological study to determine the depth of invasion of the trophoblast to the muscular layer of fallopian tube for group A. Results: 1- The serum CK level was significantly higher in group A than in group B and C and was significantly higher in ruptured than in unruptured and in isthmic compared to ampullary EP. 2- The serum progesterone level was significantly lower in group A and B than in group C, but there was no significant difference between group A and B. 3- The serum progesterone level was significantly higher in ruptured than in unruptured EP. 4- There was significant positive correlation between serum CK and progesterone level in group A. Conclusion: 1- An increase in serum CK levels probably antedates tubal rupture and could help in discriminating ruptured from unruptured EP. 2- Serum progesterone discriminates EP from normal IUP but it does not differentiate it from miscarriage. 3- The combination of both serum CK and progesterone in suspected EP has a higher differential accuracy than either analysis alone

420 Utility of three-dimensional ultrasound (3D-US) in the prediction of fetal lung maturity

To explore the predictive value of fetal lung volume (FLV), pulmonary artery resistance index (PARI) and adrenal gland volume (AGV) in the prediction of neonatal respiratory distress (RDS) in diabetic pregnancies. This is a prospective cohort study that included pregnant women with diabetes at gestational age 37 weeks or more. Singleton pregnancies that are devoid of fetal congenital anomalies were enrolled. They underwent 2D-US to record fetal biometry, estimated fetal weight (EFW) and amniotic fluid index (AFI), followed by 3D-US to evaluate FLV and AGV. A 3D-US rotational multiplanar technique was utilized for volume measurements (VOCAL), and the mean of two volumes was calculated. A pulsed Doppler signal was introduced to asses PARI. ROC curves and logistic regression models were constructed for predictability of RDS. A total of 57 diabetic pregnancies were included in the final analysis; 40 of them (70.2%) were pre-gestational diabetes. Of all, twenty-two (38.6%) newborns exhibited RDS. Comparable gestational age at delivery, EFW, neonatal birth weight, and AGV were demonstrated between neonates with and without RDS. However, neonates with RDS had higher AFI (16.3±1.9vs14.7±1.8,P<0.005) than healthy neonates. Moreover, RDS neonates showed higher PARI and lower FLV than healthy neonates (0.89±0.02vs0.83±0.04,p<0.001;24±3.6vs.31.8±5.3,p<0.001, respectively). Analysis based on the type of diabetes failed to detect any difference in FLV, AGV and PARI between women with gestational and pre-gestational diabetes. In ROC curve analysis, newborns with FLV of 28.4 or less and PARI of 0.85 or more were more likely to have RDS (AUC; 0.89 and 0.92, respectively). A predictive model that comprised both FLV and PARI would have more accuracy (89.7%) and negative predictive value (89.2%) than utilizing either measure alone. In multivariable regression analysis, only FLV was a predictor for fetal lung maturity (OR:1.8,95%CI=1.1–2.9,P<0.02). Utilizing 3D-US for measuring FLV and PRRI could serve as non-invasive accurate method for prediction of neonatal RDS in diabetic mothers.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Prediction of Late-Onset Sepsis in Preterm Infants Using Monitoring Signals and Machine Learning.

Prediction of late-onset sepsis (onset beyond day 3 of life) in preterm infants, based on multiple patient monitoring signals 24 hours before onset. Continuous high-resolution electrocardiogram and respiration (chest impedance) data from the monitoring signals were extracted and used to create time-interval features representing heart rate variability, respiration, and body motion. For each infant with a blood culture-proven late-onset sepsis, a Cultures, Resuscitation, and Antibiotics Started Here moment was defined. The Cultures, Resuscitation, and Antibiotics Started Here moment served as an anchor point for the prediction analysis. In the group with controls (C), an "equivalent crash moment" was calculated as anchor point, based on comparable gestational and postnatal age. Three common machine learning approaches (logistic regressor, naive Bayes, and nearest mean classifier) were used to binary classify samples of late-onset sepsis from C. For training and evaluation of the three classifiers, a leave-k-subjects-out cross-validation was used. Level III neonatal ICU. The patient population consisted of 32 premature infants with sepsis and 32 age-matched control patients. No interventions were performed. For the interval features representing heart rate variability, respiration, and body motion, differences between late-onset sepsis and C were visible up to 5 hours preceding the Cultures, Resuscitation, and Antibiotics Started Here moment. Using a combination of all features, classification of late-onset sepsis and C showed a mean accuracy of 0.79 ± 0.12 and mean precision rate of 0.82 ± 0.18 3 hours before the onset of sepsis. Information from routine patient monitoring can be used to predict sepsis. Specifically, this study shows that a combination of electrocardiogram-based, respiration-based, and motion-based features enables the prediction of late-onset sepsis hours before the clinical crash moment.

Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data.

Introduction: In premature neonates, the persistence of hemodynamically significant ductus arteriosus (hsPDA) can be associated with short- and long-term consequences, impairing their outcome. The correct strategy of management for such condition is under debate, especially regarding contraindications and/or side effects. In recent years, metabolomics was applied to several perinatal, pediatric, and adult conditions to investigate potential biomarkers of disease, which have become useful for early diagnosis and/or therapeutic management.Aim of the Study: The main purpose of our exploratory study was to asses, through 1H-NMR metabolomics analysis of urinary samples at birth, possible metabolic pathways differentiating, with a significant predictive power, those preterm neonates who will subsequently develop hsPDA and neonates of comparable gestational age (GA) who will undergo spontaneous ductal closure or the persistence of an irrelevant PDA (no-hsPDA). Moreover, we investigated potential prenatal or perinatal clinical factors potentially influencing the development of hsPDA.Materials and Methods: We enrolled n = 35 preterm neonates with GA between 24 and 32 weeks; urinary samples were collected within the first 12 h of life. Patients were closely monitored regarding intensive care, respiratory support, fluid balance and administered drugs; an echocardiogram was performed at 48–72 h.Results: Our results reported a significant correlation between lower GA at birth and the development of hsPDA. Moreover, neonates with GA ≤ 30w developing hsPDA were characterized by lower Apgar scores at 1′ and 5′, higher rates of perinatal asphyxia, higher need of delivery room resuscitation and subsequent surfactant administration. Interestingly, metabolomics analysis at birth detected a clear separation between the 1H-NMR urinary spectra of subjects GA ≤ 30w not developing hsPDA (n = 19) and those of subjects born at GA ≤ 30w in which hsPDA was confirmed at 48–72 h of life (n = 5).Conclusions: This is the first study applying metabolomics to investigate the PDA condition. Although preliminary and conducted on a limited sample, our results reveal that metabolomics could be a promising tool in the early identification of hsPDA, potentially superior to the clinical or laboratory predictive tools explored to date and even to the clinical observations and correlations in our sample, through the detection of specific urinary metabolites.

Metabolic Bone Disease in Premature Neonates: An Unmet Challenge

Metabolic bone disease (MBD) is an important cause of morbidity in premature, very low birth weight (VLBW) and sick infants and, if left undiagnosed, may lead to structural deformities and spontaneous fractures. MBD is defined as impaired bone mineralization in a neonate with lower than expected bone mineral levels in either a fetus or a neonate of comparable gestational age and/or weight, coupled with biochemical abnormalities with or without accompanying radiological manifestations. MBD has been reported to occur in 16% to 40% of extremely low birth weight neonates and presents by 6-16 weeks after birth. Insufficient calcium and phosphorous stores during the phase of accelerated growth predispose to MBD in neonates along with the use of some medications such as caffeine or steroids, prolonged parenteral nutrition and chronic immobilization. Enhanced physical activity in preterm infants facilitates bone mineralization and weight gain. Biochemical abnormalities tend to worsen significantly, as the severity of disease progresses. These abnormalities may include hypocalcemia, hypophosphatemia, hyperphosphatasia and secondary hyperparathyroidism. In addition, urinary phosphate wasting and hypovitaminosis D can be additional complications. Conversely, biochemical abnormalities may not be accompanied by rachitic changes. Newer diagnostic modalities include non-invasive bone densitometry by quantitative ultrasound over the mid-tibial shaft. The management of MBD includes adequate calcium, phosphorous and vitamin D supplementation, along with optimum nutrition and physical activity. Similarly, preventive strategies for MBD should target nutritional enhancement in combination with enhanced physical activity. MBD usually results in preventable morbidity in preterm and VLBW neonates. Treatment consists of optimum nutritional supplementation and enhanced physical activity.

Abstract 13078: Evaluation of Ventricular Function in Fetus With Transposition of Great Arteries by Velocity Vector Imaging

Background: The aim of this study was to test the hypotheses that (1) fetuses with complete transposition of the great arteries (D-TGA) and Taussig-Bing anomaly (TBA) has decreased the left ventricular (LV) and right ventricular(RV) mechanical function compared with normal fetuses, and (2)the decreased myocardial mechanical function in fetal D-TGA and TBA was associated with the degree of transposition of the great arteries, pulmonary stenosis(PS) and ventricular septal defect(VSD). Methods: We retrospectively identified 49 cases of fetal D-TGA and 29 cases of fetal TBA and compared findings to 49 controls of comparable gestational age. Postprocessing analysis of the left ventricle and right ventricle were done using syngo Velocity Vector Imaging version 2.3. Global and regional longitudinal systolic peak velocity, strain and strain rate were generated. Results: (1) Comparing with control group, the global and regional longitudinal systolic peak velocity (GLV), strain (GLS) and strain rate (GLSR) of the LV and RV were decreased in the group of D-TGA and TBA (P&lt;0.05). (2) In the group of D-TGA and TBA, the multivariate linear regression analysis, the VSD was the independent determinant of LVGLS and RVGLS (β = 0.270, P=0.014 and β = 0.465, P&lt; 0.001). The PS was the independent determinant of RVGLSR (β = 0.090, P=0.009). Conclusion: The ventricular function of fetal D-TGA and TBA were decreased compared with control group. The PS and VSD were the independent determinant factors of the decreased LVGLS, RVGLS and RVGLSR in the fetal D-TGA and TBA.

Association of neonatal inflammatory markers and perinatal stroke subtypes.

To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients. This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls. A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy. Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies. This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.

Fetal Middle Cerebral Artery Pulsatility Index in No-Risk Pregnancies: Effects of Auditory Stimulation and Pregnancy Order.

Pulsatility index (PI) values in a fetal middle cerebral artery (MCA) were compared in no-risk pregnancies to examine the differences related to auditory stimulation test and pregnancy order. The study included 196 women with no-risk pregnancies selected from the database of more than 1000 pregnant women divided into two groups. Group 1 consisted of 98 nulliparous women (C1 = 98) and Group 2 consisted of 98 parous women (C2 = 98). All pregnant women were of comparable age and fetal gestational age (GA) when MCA-PI values were recorded. Measurements of PI values in fetal MCA were obtained before and immediately after the application of fetal auditory stimulation test. The MCA-PI measuring was conducted in the period between the 36th and the 41st week of GA. The results showed that PI baseline values and PI values after defined auditory stimulation were significantly different when measured in nulliparous women compared to parous women (p = 0.001; p = 0.003, respectively), while no group differences were observed in relative PI value changes due to auditory stimulation. These findings suggest that hemodynamic changes in fetal MCA caused by defined auditory stimulation measured by PI value changes may be valuable in the assessment of fetal auditory perception functionality and its development.