Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Corpus callosum-fastigium and tectal lengths in late-onset small fetuses.

OBJECTIVE: To investigate measurements on neurosonography of midbrain morphology, including corpus callosum-fastigium length and tectal length, in late-onset small fetuses subclassified as small-for-gestational-age (SGA) or growth-restricted (FGR). METHODS: This was a case-control study of consecutive singleton pregnancies delivered at term at a single center between January 2019 and July 2021, including those with late-onset smallness (estimated fetal weight (EFW) < 10th centile) and appropriate-for-gestational-age controls matched by age at neurosonography. Small fetuses were further subdivided into SGA (EFW between 3rd and 9th centile and normal fetoplacental Doppler) and FGR (EFW < 3rd centile or EFW < 10th centile with abnormal cerebroplacental ratio and/or uterine artery Doppler). Transvaginal neurosonography was performed at a mean ± SD gestational age of 33 ± 1 weeks in all fetuses to evaluate corpus callosum-fastigium length and tectal length in the midsagittal plane. Intra- and interobserver agreement was evaluated using the intraclass correlation coefficient and Bland-Altman plots. RESULTS: A total of 70 fetuses with late-onset smallness (29 with SGA and 41 with FGR) and 70 controls were included. Compared with controls, small fetuses showed significantly shorter corpus callosum-fastigium length (median (interquartile range), 44.7 (43.3-46.8) mm vs 43.7 (42.4-45.5) mm, P < 0.001) and tectal length (mean ± SD, 10.5 ± 0.9 vs 9.6 ± 1.0 mm, P < 0.001). These changes were more prominent in FGR fetuses, with a linear trend across groups according to severity of smallness. Corpus callosum-fastigium length and tectal length measurements showed excellent intra- and interobserver reliability. CONCLUSIONS: Small fetuses exhibited shorter corpus callosum-fastigium length and tectal length compared with controls, and these differences were more pronounced in fetuses with more severe smallness. These findings illustrate the potential value of midbrain measurements assessed on neurosonography as biomarkers for brain development in a high-risk population. However, further studies correlating these parameters with postnatal functional tests and follow-up are needed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non-placental origin.

OBJECTIVE: To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non-malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. METHODS: This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. RESULTS: Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below -2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3-38.5) weeks and median birth weight was 2020 (IQR, 1908-2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. CONCLUSION: Non-malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). METHODS: A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). RESULTS: Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. CONCLUSION: Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Placental chemical elements concentration in small fetuses and its relationship with Doppler markers of placental function.

INTRODUCTION: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. METHODS: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. RESULTS: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. DISCUSSION: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.

Ten-year experience of protocol-based management of small-for-gestational-age fetuses: perinatal outcome in late-pregnancy cases diagnosed after 32 weeks.

OBJECTIVE: To report our 10-year experience of protocol-based management of small-for-gestational-age (SGA) fetuses, based on standardized clinical and Doppler criteria, in late-pregnancy cases. METHODS: A retrospective cohort was constructed of consecutive singleton pregnancies referred for late-onset (> 32 weeks) SGA (defined as estimated fetal weight (EFW) < 10th centile) that were classified as fetal growth restriction (FGR) or low-risk SGA, based on the severity of smallness (EFW < 3rd centile) and the presence of Doppler abnormalities (uterine artery pulsatility index (UtA-PI) ≥ 95th centile or cerebroplacental ratio (CPR) < 5th centile). Low-risk SGA pregnancies were followed at 2-week intervals and delivered electively at 40 weeks. FGR pregnancies were followed at 1-week intervals, or more frequently if there were signs of fetal deterioration, and were delivered electively after 37 + 0 weeks' gestation. The occurrence of stillbirth and composite adverse outcome (CAO; defined as neonatal death, metabolic acidosis, need for endotracheal intubation or need for admission to the neonatal intensive care unit) was analyzed in low-risk SGA and FGR pregnancies. RESULTS: A total of 1197 pregnancies with EFW < 10th centile were identified and classified at diagnosis as low-risk SGA (n = 619; 51.7%) or FGR (n = 578; 48.3%). Of these, 160 were delivered before 37 weeks' gestation; for obstetric reasons in 93 (58.1%) cases, severe pre-eclampsia in 33 (20.6%), FGR with severe hypoxia in 47 (29.4%) and stillbirth in four (2.5%) (indications are non-exclusive). During follow-up, 52/574 (9.1%) low-risk SGA pregnancies were reclassified as FGR, whereas 22/463 (4.8%) FGR pregnancies were reclassified as low-risk SGA. Overall, there were no stillbirths in the low-risk SGA group and four in the FGR group, all of which occurred before 37 weeks. There were no instances of neonatal death in pregnancies delivered ≥ 37 weeks. The risk of CAO was higher in those meeting antenatal criteria for FGR at 37 weeks than in those classified as low-risk SGA (32/493 (6.5%) vs 15/544 (2.8%); odds ratio, 2.5 (95% CI, 1.3-4.6)). In FGR pregnancies, the adjusted odds ratio (95% CI) for CAO was 6.3 (1.8-21.1) in those with EFW < 3rd centile, while it was 3.2 (1.5-6.8) and 4.2 (1.9-8.9) in those with UtA-PI ≥ 95th centile and CPR < 5th centile, respectively, as compared to FGR pregnancies without each of these criteria. CONCLUSION: Protocol-based risk stratification with different management and monitoring schemes for late pregnancy with a suspected SGA baby, based on clinical and Doppler criteria, enables identification and tailored assessment of high-risk FGR, while allowing expectant management with safe perinatal outcome for low-risk SGA fetuses. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study.

OBJECTIVE: To assess in women with early-onset severe pre-eclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome. DESIGN: Prospective cohort study. SETTING: Maternity units in two Spanish hospitals. POPULATION: Women with diagnosis of early-onset severe pre-eclampsia. METHODS: Levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-) and sFlt-1/PlGF ratio were measured at admission and before delivery, and average daily change calculated. The association of longitudinal changes of angiogenic factors with the time interval to delivery and with complications was evaluated by logistic and Cox regression. MAIN OUTCOME MEASURES: Interval to delivery and composite of adverse outcomes. RESULTS: We included 63 women, of which 26 (41.3%) had a complication. Longitudinal changes of sFlt-1 were more pronounced in complicated pregnancies (median: 1047 versus 342 pg/ml/day; P = 0.04). On the multivariate analysis, the clinical risk score and sFlt-1 at admission explained 6.2% of the uncertainty for complication; the addition of sFlt-1 longitudinal changes improved this to 25.3% (P = 0.002). The median time from admission to delivery was 4 days (95% CI 1.6-6.04) in those in the highest quartile of sFlt-1 longitudinal changes versus 16 days (95% CI 12.4-19.6) in the remaining women (Log-rank test P < 0.001). CONCLUSIONS: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe pre-eclampsia add to baseline characteristics in the prediction of adverse outcome and interval to delivery. TWEETABLE ABSTRACT: In early-onset severe pre-eclampsia, longitudinal changes in sFlt-1 levels improve the prediction of complications and interval to delivery.

Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu.

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

Hemispherical differences in the shape and topography of asteroid (101955) Bennu.

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

Ground and In-Flight Calibration of the OSIRIS-REx Camera Suite.

The OSIRIS-REx Camera Suite (OCAMS) onboard the OSIRIS-REx spacecraft is used to study the shape and surface of the mission's target, asteroid (101955) Bennu, in support of the selection of a sampling site. We present calibration methods and results for the three OCAMS cameras-MapCam, PolyCam, and SamCam-using data from pre-flight and in-flight calibration campaigns. Pre-flight calibrations established a baseline for a variety of camera properties, including bias and dark behavior, flat fields, stray light, and radiometric calibration. In-flight activities updated these calibrations where possible, allowing us to confidently measure Bennu's surface. Accurate calibration is critical not only for establishing a global understanding of Bennu, but also for enabling analyses of potential sampling locations and for providing scientific context for the returned sample.

Shape of (101955) Bennu indicative of a rubble pile with internal stiffness.

The shapes of asteroids reflect interplay between their interior properties and the processes responsible for their formation and evolution as they journey through the Solar System. Prior to the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission, Earth-based radar imaging gave an overview of (101955) Bennu's shape. Here, we construct a high-resolution shape model from OSIRIS-REx images. We find that Bennu's top-like shape, considerable macroporosity, and prominent surface boulders suggest that it is a rubble pile. High-standing, north-south ridges that extend from pole to pole, many long grooves, and surface mass wasting indicate some low levels of internal friction and/or cohesion. Our shape model indicates that, similar to other top-shaped asteroids, Bennu formed by reaccumulation and underwent past periods of fast spin leading to its current shape. Today, Bennu might follow a different evolutionary pathway, with interior stiffness permitting surface cracking and mass wasting.

Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

OBJECTIVES: To investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test. METHODS: This is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe preeclampsia. Controls had at least two normal, spontaneously conceived pregnancies at term, without complications or no underlying medical disease. At least 3 months after delivery, all case and control women underwent blood collection for standard blood tests for thrombophilias and saliva collection for the genetic test, which enables the diagnosis of 12 hereditary thrombophilias by analyzing genetic variants affecting different points of the blood coagulation cascade. RESULTS: The study included 33 cases and 41 controls. There were no statistically significant differences between cases and controls in the standard blood tests for thrombophilias in plasma or the TiC test for genetic variables. One clinical-genetic model was generated using variables with the lowest P values: ABO, body mass index, C_rs5985, C_rs6025, and protein S. This model exhibited good prediction capacity, with an area under the curve of almost 0.7 (P <0.05), sensitivity of almost 67%, and specificity of 70%. CONCLUSION: Although some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in subsequent pregnancies.

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements.

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

Associations between neural injury markers of intrauterine growth-restricted infants and neurodevelopment at 2 years of age.

Objectives: The aim of this study was to evaluate the relationships between brain injury biomarkers in intrauterine growth-restricted (IUGR) infants (S100B and neuron-specific enolase (NSE)) and neurodevelopment at 2 years of age. Methods: This prospective case-control study was a cooperative effort among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler variables were measured for each infant. Maternal venous blood and fetal umbilical arterial blood samples were collected at the time of delivery and neural injury markers S100B and NSE concentrations were measured. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). Results: Fifty six pregnancies were included. Thirty-one infants were classified as IUGR and 25 as non-IUGR. Neurodevelopmental evaluation at 2 years of age indicated that there were no between-group differences for any of the tests. For all patients in both groups, we found statistically significant inverse relationships between the concentrations of NSE in the cord blood and the results of the cognitive test (r = -271, p = .042), fine motor subtest (r = -280, p = .036), and social-emotional test (r = -349, p = .015). We also found statistically significant differences between the concentrations of S100B in the cord blood and the results of the cognitive test (r = -306, p = .022) and expressive communication subtest (r = -304, p = .023). For the IUGR group, we found a significant inverse relationship between the concentrations of S100B in the maternal serum and the results of adaptive behavior test (p < .05). In the non-IUGR group, we found statistically significant inverse relationships between the concentration of NSE in the cord blood and the results of the fine motor subtest (r = -446, p = .025) and social-emotional test (r = -489, p = .021). The difference between the concentration of S100B in the cord blood and the language composite score was also statistically significant (p = .038). Conclusions: At 2 years of age, the concentrations of NSE and S100B were higher in the non-IUGR and IUGR groups with the worst scores for some areas of neurodevelopmental evaluation. The value of these biomarkers for prognostic neurodevelopmental use requires further investigation for both non-IUGR and IUGR infants.

In-flight characterization of the lunar orbiter laser altimeter instrument pointing and far-field pattern.

The Lunar Orbiter Laser Altimeter (LOLA) aboard the Lunar Reconnaissance Orbiter (LRO) has collected nearly seven billion measurements of surface height on the Moon with an absolute accuracy of ∼1 m and a precision of ∼10 cm. Converting time-of-flight laser altimeter measurements to topographic elevations requires accurate knowledge of the laser pointing with respect to the spacecraft body-fixed coordinate system. To that end, we have utilized altimetric crossovers from LOLA, as well as bidirectional observations of the LOLA laser and receiver boresight via an Earth-based laser tracking ground station. Based on a sample of ∼780,000 globally distributed crossovers from the circular-orbit phase of LRO's mission (∼27 months), we derive corrections to the LOLA laser boresight. These corrections improve the cross-track and along-track agreement of the crossovers by 24% and 33%, respectively, yielding RMS residuals of ∼10 m. Since early in the LRO mission, the bidirectional laser tracking experiments have confirmed a pointing anomaly when the LOLA instrument is facing toward deep space or the night side of the Moon and have allowed the reconstruction of the laser far-field pattern and receiver telescope pointing. By conducting such experiments shortly after launch and nearly eight years later, we have directly measured changes in the laser characteristics and obtained critical data to understand the laser behavior and refine the instrument pointing model. The methods and results presented here are also relevant to the design, fabrication, and operation of future planetary laser altimeters and their long-term behavior in the space environment.

Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small-for-gestational age.

OBJECTIVE: Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small-for-gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA-suspected fetuses. METHODS: This was a prospective cohort study of consecutive singleton pregnancies with late (diagnosis ≥ 32.0 weeks) SGA (estimated fetal weight (EFW) < 10th centile). Longitudinal growth assessment was performed by calculation of EFW z-velocity between diagnosis and last scan before delivery. Improvement in the association with and predictive performance of EFW z-velocity for adverse perinatal outcome was compared against standard criteria of FGR evaluated before delivery (EFW < 3rd centile, abnormal uterine Doppler or abnormal cerebroplacental ratio). RESULT: A total of 472 patients were evaluated prospectively for suspected SGA. Of these, 231 (48.9%) qualified as late FGR. Univariate analysis showed a significant trend towards higher frequency (14.5% vs 8.2%; P = 0.041) of EFW z-velocity in the lowest decile in pregnancies with adverse perinatal outcome. Nonetheless, the addition of EFW z-velocity improved neither the association with nor the predictive performance of standard criteria of FGR for adverse perinatal outcome. CONCLUSIONS: Longitudinal assessment of fetal growth by means of EFW z-velocity did not have any independent predictive value for adverse perinatal outcome when used in combination with Doppler in SGA-suspected fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Second- to third-trimester longitudinal growth assessment for prediction of small-for-gestational age and late fetal growth restriction.

OBJECTIVE: Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross-sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second- to third-trimester longitudinal growth assessment to cross-sectional evaluation in the third trimester for the prediction of small-for-gestational age (SGA) and late FGR in low-risk singleton pregnancy. METHODS: This was a prospective cohort study of 2696 unselected consecutive low-risk singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks. For cross-sectional growth assessment, abdominal circumference (AC) measurements were transformed to z-values according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by calculating the AC z-velocity and the second- to third-trimester AC conditional growth centile. Longitudinal assessment was compared with cross-sectional assessment at 32 weeks. Association of cross-sectional and longitudinal evaluations with SGA and late FGR was assessed by logistic regression analysis. Predictive performance was determined by receiver-operating characteristics curve analysis. RESULT: In total, 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. Neither longitudinal measurement improved the association with SGA or late FGR provided by cross-sectional evaluation of AC z-score at 32 weeks. Areas under the curves of AC z-velocity and conditional AC growth were significantly smaller than those of cross-sectional AC z-scores (P < 0.001), although AC z-velocity performed significantly better than did conditional AC growth (P < 0.001). CONCLUSION: Longitudinal assessment of fetal growth from the second to third trimester has a low predictive capacity for SGA and late FGR in low-risk singleton pregnancy compared with cross-sectional growth evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Neural injury markers in intrauterine growth restriction and their relation to perinatal outcomes.

BACKGROUNDThe aims of this study were to (i) compare the concentrations of two neural injury markers, S100B protein and neuron-specific enolase (NSE), in intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate growth-for-gestational-age (AGA), and (ii) investigate potential relationships between concentrations of these markers, Doppler abnormalities, and adverse perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative, prospective study among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler were measured. At the time of delivery, maternal venous blood and fetal umbilical arterial blood samples were collected. S100B and NSE concentrations were determined from these samples.RESULTSIn total, 254 pregnancies were included. Among these, 147 were classified as IUGR and 107 as AGA. There were no differences between the groups in S100B concentrations. However, levels of NSE in maternal and umbilical cord serum differed significantly between these groups (2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR (P<0.05), respectively). No differences were observed in these neurological markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough some variations exist in these neurological markers, they did not correlate with perinatal or neonatal complications.

Risk factors to develop multicentric lesions of the lower genital tract.

Purpose ofinvestigation: To analyze which are the risk factors in developing multicentric lesions of lower genital tract. MATERIALS AND METHODS: A prospective study of 1,011 patients was conducted at the low genital tract pathology clinic of Sant Joan de Deu Hospital between 2003-2011. A complete assessment of cervix, vagina, and vulva was carried out including HPV-DNA testing, cytology study, colposcopy, and biopsy in case of atypical findings. The statistical analysis was done with SPSS v.19 software. Differences between groups were considered statistically significant atp < 0.05. RESULTS: Twenty-two patients presented multicentric lesions (2.2%). The average age was 43 years. Most of the lesions were bicentric affecting cervix and vagina and cervix and vulva. Only in two cases (9%) there were three sites of genital neoplasia. The authors found four cervical cancer, 17 high grade, and one low grade lesions of the cervix. Eighteen vaginal intraepithelial neoplasia (VAIN), six high grade, 14 low grade, and four vulvar intraepithelial neoplasia (VIN) were found. HPV infection, age > 35 years, multiparity, contraceptive method, immunodeficiency, and level of studies were significantly correlated with multicentric lesions. High percentage of affected margins were found. VIN cases were treated with surgical excision and in two cases microinvasion was found. VAIN III cases were treated with surgical excision or with laser and one case progressed to vaginal cancer. Recurrence after treatment was 27%. CONCLUSION: Age, multiparity, contraceptive method, immunodeficiency, and level of studies were significantly correlated with multicentric lesion. Multicentric lesions had an increased risk of recurrence and progression to cancer.