Normal Umbilical Artery Research Articles

Gender-specific reference charts for cardiotocographic parameters throughout normal pregnancy: a retrospective cross-sectional study of 9701 fetuses

ObjectiveTo establish reference values for cardiotocographic (CTG) parameters from 24 to 41 weeks of gestation in normal pregnancies. Study designRetrospective cross-sectional study, using the first antepartum tracing of singleton fetuses with normal pregnancy outcomes (term birth, normal birthweight, normal umbilical artery pH and Apgar scores, no intensive care unit admission). Cases were consecutively selected from a hospital electronic patient record, and analyzed using the OmniviewSisPorto 3.7 system. Variables were compared between male and female fetuses, by gestational age, and percentile curves were constructed. ResultsA total of 9701 tracings (corresponding to 9701 fetuses) were analyzed. All CTG parameters changed significantly throughout gestation in both genders, with a decrease in baseline and decelerations, and an increase in average long-term variability (LTV), average short-term variability (STV), accelerations and uterine contractions. The mean baseline value decreased 9bpm, and its range almost doubled from 24 to 40 weeks. Until 30 weeks the lower percentiles for average LTV were below 5bpm, and the minimum value for average STV was never below 1bpm. The proportion of tracings without accelerations decreased from 30.1% at 24-25 weeks to 0.5% at 39 weeks. The median number of decelerations was practically zero for all gestational ages. All CTG variables, except decelerations and uterine contractions, showed statistically significant gender differences: baseline was consistently higher in females, while average LTV and average STV tended to be lower in females throughout most of pregnancy. Separate percentile curves were constructed for male and female fetuses. ConclusionThis study provides reference values for CTG parameters throughout pregnancy, derived from the largest dataset of healthy fetuses published to date. For the first time, gender differences were clearly demonstrated in fetal life, and percentile curves constructed separately for male and female fetuses.

Colour Doppler Study of Umbilical Artery in Antenatal Women with Severe Preeclampsia and Foetal Outcome

Hypertensive disorders are the most common medical complications of pregnancy (7.15%). Doppler analysis of umbilical artery S/D ratio PI and RI, absent or reversal of EDV were evaluated and follow up results studied in severe preeclampsia women between 26 to 40 weeks. Doppler analysis of Uterine Artery and Middle Cerebral Artery is also studied. Doppler study guides in decision making and follows up in severe preeclampsia and guides in reducing perinatal morbidity and mortality. Period of Study: This is a prospective randomised study conducted at Niloufer Hospital for Women and Children Red Hills Hyderabad from September 2011 to June 2014. Material and Methods: 100 pregnant women with severe preeclampsia who attended Antenatal Out-Patient Department and got admitted in Emergency ward underwent Umbilical artery velocimetry by means of a Colour doppler vision (6000 Toshiba corp Tokyo Japan) using 3.5_5 MHZ Trasabdominal traducer. Results: Total number of 100 women were studied. In this 60 women had foetuses with abnormal umbilical artery flow velocimetry and 40 had normal umbilical artery flow velocimetry. The average birth weight and diagnosis to delivery interval were lower in foetuses with abnormal umbilical artery doppler. Admission to neonatal intensive care unit is high. The APGAR score at 1 minute is <7 in 20 women with abnormal umbilical artery doppler compared to 17 women with normal umbilical artery doppler. Compared to 32 women with normal umbilical artery doppler, the APGAR score is more than 7 in 31 women with abnormal umbilical artery Doppler. P = 0.639647 and chi-square statistic = 0.2192, the result is statistically not significant at p-value < 0.05, implying that APGAR scores are not dependent on doppler findings alone. Conclusion: Doppler study guides obstetrician to assess the physiological status of the foetus and it helps in identifying the changes in the foetal circulation. This study suggests that doppler assessment of foe to placental circulation including umbilical artery is a better prognostic indicator in severe PE and helps in timely intervention. The foetuses with normal artery flow velocimetry area at a lower risk of having poor APGAR score than those with abnormal velocimetry and NICU admissions are less with normal umbilical artery flow velocimetry. The average birth weight of neonates with abnormal umbilical artery was lower compared to neonates with normal umbilical artery velocimetry.

Cervical condition and fetal cerebral Doppler as determinants of adverse perinatal outcome after labor induction for late-onset small-for-gestational-age fetuses.

To estimate the combined value of fetal cerebral Doppler examination and Bishop score for predicting perinatal outcome after labor induction for small-for-gestational-age (SGA) fetuses in the presence of normal umbilical artery Doppler recordings. We conducted a cohort study in two tertiary centers, including 164 women with normal umbilical artery Doppler recordings who underwent induction of labor because of an estimated fetal weight < 10(th) percentile. The fetal middle cerebral artery pulsatility index and cerebroplacental ratio (CPR) were obtained in all cases within 24 h before induction. Cervical condition was assessed at admission using the Bishop score. A predictive model for perinatal outcomes was constructed using a decision-tree analysis algorithm. Both a very unfavorable cervix, defined as a Bishop score < 2, (odds ratio (OR), 3.18; 95% CI, 1.28-7.86) and an abnormal CPR (OR, 2.54; 95% CI, 1.18-5.61) were associated with an increased likelihood of emergency Cesarean section for fetal distress, but only the latter was significantly associated with the need for neonatal admission (OR, 2.43; 95% CI, 1.28-4.59). In the decision-tree analysis, both criteria significantly predicted the likelihood of Cesarean section for fetal distress. Combined use of the Bishop score and CPR improves the ability to predict overall Cesarean section (for any indication), emergency Cesarean section for fetal distress, and neonatal admission after labor induction for late-onset SGA in the presence of normal umbilical artery Doppler recordings.

Neurodevelopmental outcome in very low birthweight infants with pathological umbilical artery flow

ObjectiveTo assess neurodevelopmental outcome during toddlerhood in very low birthweight (VLBW) infants with absent or reverse end-diastolic flow (AREDF) in the umbilical artery (UA) during pregnancy.DesignRetrospective cohort study with matched...

Association of brain metabolism with sulcation and corpus callosum development assessed by MRI in late-onset small fetuses

We sought to determine the relationship between fetal brain metabolism and microstructure expressed by brain sulcation, and corpus callosum (CC) development assessed by fetal brain magnetic resonance (MR) imaging and proton MR spectroscopy ((1)H-MRS). A total of 119 fetuses, 64 that were small for gestational age (estimated fetal weight <10th centile and normal umbilical artery Doppler) and 55 controls underwent a 3T MR imaging/(1)H-MRS exam at 37 weeks. Anatomical T2-weighted images were obtained in the 3 orthogonal planes and long echo time (TE) (1)H-MRS acquired from the frontal lobe. Head biometrics, cortical fissure depths (insula, Sylvian, parietooccipital, cingulate, and calcarine), and CC area and biometries were blindly performed by manual and semiautomated delineation using Analyze software and corrected creating ratios for biparietal diameter and frontooccipital diameter, respectively, for group comparison. Spectroscopic data were processed using LCModel software and analyzed as metabolic ratios of N-acetylaspartate (NAA) to choline (Cho), Cho to creatine (Cr), and myo-inositol (Ino) to Cho. Differences between cases and controls were assessed. To test for the association between metabolic ratios and microstructural parameters, bivariate correlation analyses were performed. Spectroscopic findings showed decreased NAA/Cho and increased Cho/Cr ratios in small fetuses. They also presented smaller head biometrics, shorter and smaller CC, and greater insular and cingulate depths. Frontal lobe NAA/Cho significantly correlated with biparietal diameter (r = 0.268; P = .021), head circumference (r = 0.259; P = .026), CC length (r = 0.265; P = .026), CC area (r = 0.317; P = .007), and the area of 6 from the 7 CC subdivisions. It did not correlate with any of the cortical sulcation parameters evaluated. None of the other metabolic ratios presented significant correlations with cortical development or CC parameters. Frontal lobe NAA/Cho levels-which are considered a surrogate marker of neuronal activity-show a strong association with CC development. These results suggest that both metabolic and callosal alterations may be part of the same process of impaired brain development associated with intrauterine growth restriction.

Correlation between histological signs of placental underperfusion and perinatal morbidity in late-onset small-for-gestational-age fetuses.

To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer an increased risk of neonatal morbidity in late-onset small-for-gestational-age (SGA) fetuses with normal umbilical artery (UA) Doppler indices. A cohort of 126 SGA singleton fetuses with normal UA Doppler indices that were delivered after 34 weeks' gestation was studied. For each case, the placenta was evaluated histologically for signs of PUP using a hierarchical and standardized classification system. Neonatal morbidity was assessed according to the score calculated from the morbidity assessment index for newborns (MAIN), a validated outcome scale. The independent association between PUP and neonatal morbidity was evaluated using multivariable median regression analysis. In 84 (66.7%) placentae, 97 placental histological findings that qualified as signs of PUP were observed. These PUP cases had a significantly higher incidence of emergency Cesarean section for non-reassuring fetal status (44.1% vs 21.4%, respectively; P = 0.013) and neonatal metabolic acidosis at birth (33.3% vs 14.3%, respectively; P = 0.023), than did those without PUP. The median MAIN score differed significantly between those with PUP and those without (89 vs 0, respectively; P = 0.025). This difference remained significant after adjustment for potential confounders. The proportion of cases with scores indicative of mild to severe morbidity was also significantly higher in the PUP group (31% vs 14.3%, respectively; P = 0.043). In late-onset SGA fetuses with normal UA Doppler indices, signs of PUP imply a higher neonatal morbidity. These findings allow the phenotypic profiling of fetal growth restriction among the general population of late-onset SGA.

Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. UtA Doppler indices predict adverse perinatal outcome, but do not help to improve the predictive value of brain Doppler indices. However, at the time of SGA diagnosis they identify the subgroup of fetuses at highest risk of progression to abnormal brain Doppler findings.

Umbilical Cord Blood CD33 and Erythropoietin Levels of Pregnants with Abnormal Doppler Waveforms and to Compare with Normal Pregnancies

Objective: In this study, we aimed to investigate umbilical cord blood CD33 and erythropoietin (EPO) levels of pregnants with abnormal umbilical and uterine artery doppler waveforms and to compare with normal pregnancies. Materials and Methods: Total 40 pregnant women were included in this study. Of these 40 women, while 20 patients had abnormal umbilical and uterine artery doppler waveforms, the other 20 patients had normal umbilical and uterine artery doppler waveforms. After the delivery, blood samples were taken from umbilical artery of double clemped umbilical cord for blood gas parameters, EPO and CD33 levels. Sociodemographic findings, antepartum, intrapartum test results, labor and delivery characteristics and newborn examination results were recorded. Blood gas parameters, EPO and CD33 levels between groups were analyzed. Mann-Whitney U test and t-test were used as statistical methods. Results: There were no differences between parity, gestational ages and newborn weights of the groups. Cord blood CD33 and EPO levels of group with abnormal umbilical and uterine artery doppler waveforms were significantly higher than group with normal umbilical and uterine artery doppler waveforms (p < 0.01). Conclusion: Pathology on doppler screen shows to us a connection between chronic hypoxemia and abnormal on doppler screen. Preference of high blood CD33 levels for cord blood transplantation especially during last years can also be used with preference of cord blood with abnormal doppler findings.

OP08.07: Cerebroaortic ratio: a new index for the prediction of adverse perinatal outcome in term small‐for‐gestational age fetuses with normal umbilical artery Doppler

To evaluate the clinical value of cerebroaortic ratio in predicting the risk of Caesarean section (CS) non-reassuring fetal status (NRFS) in term small-for-gestational-age (SGA) fetuses with normal umbilical artery Doppler. Combination of middle cerebral artery (MCA) and Aortic Isthmus (AoI) pulsatility indices (PI) in the cerebroaortic ratio (CAR = MCA/AoI) was evaluated within 1 week before labour induction in a cohort of 106 singleton consecutive SGA fetuses with normal umbilical artery PI (<95th centile) delivered above 37 weeks. The contribution of CAR to predict CS for NRFS alone or in combination with MCA PI, cerebroplacental ratio (CPR), AoI PI and uterine artery Doppler was assessed by logistic regression and decision tree analysis. Individual Doppler abnormalities were significantly associated with the risk of CS for NRFS, with an odds ratio (OR) of 4.9 (95% confidence intervals (CI) 4.9-11.9, p < 0.001) for abnormal CAR (<0.48), OR of 4.2 (95% CI 1.6-10.7, p = 0.003) for abnormal MCA (<5th centile), OR of 3.9 (95% CI 1.6-9.8, p = 0.003) for abnormal CPR (<5th centile) and OR of 2.8 (95% CI 1.1-7.3, p = 0.03) for abnormal uterine artery Doppler (mean PI >95th centile). Decision tree analysis combining abnormalities in CAR, MCA, CPR, and uterine artery Doppler identified the CAR as the best individual predictor discriminating two groups with high (51.0%) and low risk (17.5%). Combination of brain Doppler and Aortic Isthmus in the cerebroaortic ratio better discriminates term SGA fetuses at risk of adverse perinatal outcome.

Proton Magnetic Resonance Spectroscopy Assessment of Fetal Brain Metabolism in Late-Onset ‘Small for Gestational Age' versus ‘Intrauterine Growth Restriction' Fetuses

Objectives: We used magnetic resonance spectroscopy (MRS) to evaluate brain metabolic differences in small fetuses near term as compared to appropriate for gestational age (AGA) fetuses. Study Design: 71 term small fetuses (estimated fetal weight <10th centile for gestational age with normal umbilical artery Doppler sonography) were subclassified as late intrauterine growth restriction (IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65 AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal uterine artery Doppler sonography or estimated fetal weight <3rd centile. All participants underwent brain magnetic resonance imaging at 37 weeks of gestation, and single-voxel magnetic resonance spectra were obtained from the frontal lobe on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr) and Cho/Cr ratios were calculated and compared between cases and controls. The association of the metabolic ratios with the study groups was tested. Results: After MRS processing and applying quality control criteria, 31 spectra from late-onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear trend across the three clinical groups that were considered. Conclusions: Both SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios. The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are not constitutionally small and may represent a form of growth disorder that needs to be clarified.

Defining the residual risk of adverse perinatal outcome in growth-restricted fetuses with normal umbilical artery blood flow

We sought to determine the cause of adverse perinatal outcome in fetal growth restriction (FGR) where umbilical artery (UA) Doppler was normal, as identified from the Prospective Observational Trial to Optimize Pediatric Health (PORTO). We compared cases of adverse outcome where UA Doppler was normal and abnormal. The PORTO study was a national multicenter study of >1100 ultrasound-dated singleton pregnancies with an estimated fetal weight <10th centile. Each pregnancy underwent intensive ultrasound, including multivessel Doppler. UA Doppler was considered abnormal when the pulsatility index was >95th centile or end-diastolic flow was absent/reversed. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, or death. In all, 57 (5.0%) of the 1116 fetuses had an adverse perinatal outcome. Nine (1.3%) of 698 fetuses with normal UA Doppler had an adverse outcome, compared with 48 (11.5%) of 418 with abnormal UA Doppler (P < .0001). There were 2 perinatal deaths in the normal group and 6 in the abnormal group (P = .01). The perinatal deaths in the normal group were 1 case of pulmonary hypoplasia after prolonged preterm rupture of the membranes from 12 weeks' gestation and a case of placental abruption. Gestation at delivery was 33 ± 3 vs 31 ± 4 weeks (P = .05) and mean birthweight was 1830 ± 737 vs 1146 ± 508 g (P = .001) in the respective groups. Neonatal sepsis was the commonest adverse outcome in both groups: 0.1% and 0.4%, respectively (P = .01). Adverse perinatal outcome is uncommon in FGR with normal UA Doppler. The cases we identified were associated with heterogenous pathologies. FGR with normal UA blood flow is a largely benign condition.

Doppler Ultrasonography

INTRODUCTION: Fetuses with growth delay at risk for complications may not be identified if further evaluation is limited to fetuses with an estimated fetal weight less than the 10th percentile. We assessed umbilical artery Doppler in fetuses at the 10–20th percentile to identify those at risk for poor perinatal outcomes. METHODS: Retrospective cohort evaluating fetuses with estimated fetal weight 10th–20th percentile on ultrasonography, January 2002 to January 2012. Exclusion criteria were delivery at an outside hospital, multiple gestations fetal anomalies, and lack of umbilical artery evaluation. Ultrasound reports were reviewed and perinatal outcomes ascertained from medical records. Umbilical artery was abnormal if systolic or diastolic ratio was elevated or there was absent or reversed end diastolic flow. Composite neonatal outcome was defined as 5-minute Apgar less than 7, arterial cord pH less than 7.0, or intubation. χ2 test was used for categorical variables and t test for continuous. Multiple logistic regression was used to control for statistically significant variables. RESULTS: Five hundred twenty-nine fetuses met inclusion and exclusion criteria. Ninety-one fetuses had abnormal umbilical artery and 438 normal. Neonates with estimated fetal weight 10th–20th percentile and abnormal umbilical artery had a threefold to sixfold increase in preterm birth, preeclampsia, low birth weight, and neonatal intensive care unit admission, whereas poor composite neonatal outcome was almost nine times greater than in fetuses with normal umbilical artery (Table 1). These findings remained statistically significant when controlling for gestational age at ultrasonography, delivery, and maternal age.CONCLUSIONS: Doppler ultrasonography in fetuses with growth in the 10th–20th percentile can help identify those at increased risk for low birth weight, preterm birth, preeclampsia, neonatal intensive care unit admission, and poor neonatal composite.

Maternal serum analytes as predictors of IUGR with different degrees of placental vascular dysfunction

Our primary objective was to determine the association of maternal serum analytes in pregnancies complicated by intrauterine growth restriction (IUGR) stratified by umbilical artery (UA) Doppler versus pregnancies with appropriately grown for gestational age (AGA) and its potential use as screening model. Retrospective cohort evaluating first and second trimester maternal serum aneuploidy screening markers in women complicated with IUGR [90 with absent or reversed end diastolic velocity (AREDV), 46 with UA systolic/diastolic ratio ≥95th percentile and 215 with normal UA Doppler] versus 2590 women with AGA fetuses (control). Extreme levels of each analyte were significantly more common in the IUGR/AREDV group than in AGA group: inhibin A >97th percentile [≥2.27 multiples of the median (MoM)], OR: 41 (95% CI: 21-80); unconjugated estriol <3rd percentile (≤0.6 MoM), OR: 17.2 (95% CI: 8.1-42); AFP >97th percentile (≥1.88 MoM), OR: 15 (95% CI: 8.2-27); PAPP-A <3rd percentile (≤0.33 MoM), OR: 13 (95% CI: 6.6-25.5); and free-beta human chorionic gonadotrophin second trimester >97th percentile (≥3.24 MoM), OR: 11.6 (95% CI: 4.2-32). In a subgroup of pregnancies in which all markers were evaluated on each patient, a combination of abnormal markers detected 73% (95% CI: 54-87%) of IUGR/AREDV fetuses. When maternal risk factors were included into the risk calculation, it increased to 91% (95% CI: 76-98%). Abnormal maternal serum aneuploidy markers preferentially identify those pregnancies at greatest risk of IUGR with AREDV in the UA.

Clinical application of fetal left modified myocardial performance index in the evaluation of fetal growth restriction

This study aims to evaluate cardiac function in fetuses with intrauterine growth restriction (IUGR) compared with healthy fetuses, using the left modified myocardial performance index (MPI) and the association between MPI and perinatal outcome. Pregnant women between 34 and 39 weeks of gestation, who met the criteria for IUGR and were scheduled for delivery at an Egyptian tertiary medical center, were prospectively enrolled in the study. Women in the same gestational-age group with uncomplicated pregnancies were included as a control group. MPI was measured in all fetuses. The IUGR group was analyzed based on normal and abnormal umbilical artery (UA) Doppler. Perinatal outcomes were recorded. The mean left MPI was significantly higher in IUGR fetuses with abnormal UA Doppler (mean 0.58±SD 0.093) compared with healthy fetuses (mean 0.45±SD 0.070) (P<0.001). IUGR fetuses with abnormal left MPI showed significantly worse perinatal outcome and increased morbidity compared with the control group. IUGR fetuses with abnormal left MPI also showed significantly worse perinatal outcome compared with IUGR fetuses with normal MPI (whether the UA Doppler was normal or abnormal). The fetal MPI was associated with the severity of fetal compromise in IUGR fetuses based on the perinatal outcome. MPI is a potentially useful tool in evaluating fetuses with suspected IUGR, which is crucial in classifying IUGR pregnancies into critical and non-critical cases and in predicting neonatal outcome.

5:45 PM REDUCED MICROSTRUCTURAL WHITE MATTER ALTERATIONS IN PSYCHOTIC DISORDER; STABLE OR PROGRESSIVE?

We sought to determine the relationship between fetal brain metabolism and microstructure expressed by brain sulcation, and corpus callosum (CC) development assessed by fetal brain magnetic resonance (MR) imaging and proton MR spectroscopy (1H-MRS).A total of 119 fetuses, 64 that were small for gestational age (estimated fetal weight <10th centile and normal umbilical artery Doppler) and 55 controls underwent a 3T MR imaging/1H-MRS exam at 37 weeks. Anatomical T2-weighted images were obtained in the 3 orthogonal planes and long echo time (TE) 1H-MRS acquired from the frontal lobe. Head biometrics, cortical fissure depths (insula, Sylvian, parietooccipital, cingulate, and calcarine), and CC area and biometries were blindly performed by manual and semiautomated delineation using Analyze software and corrected creating ratios for biparietal diameter and frontooccipital diameter, respectively, for group comparison. Spectroscopic data were processed using LCModel software and analyzed as metabolic ratios of N-acetylaspartate (NAA) to choline (Cho), Cho to creatine (Cr), and myo-inositol (Ino) to Cho. Differences between cases and controls were assessed. To test for the association between metabolic ratios and microstructural parameters, bivariate correlation analyses were performed.Spectroscopic findings showed decreased NAA/Cho and increased Cho/Cr ratios in small fetuses. They also presented smaller head biometrics, shorter and smaller CC, and greater insular and cingulate depths. Frontal lobe NAA/Cho significantly correlated with biparietal diameter (r = 0.268; P = .021), head circumference (r = 0.259; P = .026), CC length (r = 0.265; P = .026), CC area (r = 0.317; P = .007), and the area of 6 from the 7 CC subdivisions. It did not correlate with any of the cortical sulcation parameters evaluated. None of the other metabolic ratios presented significant correlations with cortical development or CC parameters.Frontal lobe NAA/Cho levels–which are considered a surrogate marker of neuronal activity–show a strong association with CC development. These results suggest that both metabolic and callosal alterations may be part of the same process of impaired brain development associated with intrauterine growth restriction.

Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion

ObjectiveTo evaluate 2-year neurodevelopmental outcomes of near-term, small-for-gestational-age (SGA) newborns segregated by presence or absence of histopathology reflecting placental underperfusion (PUP). Patients and methodsA cohort of consecutive near-term (≥34.0 weeks) SGA newborns with normal prenatal umbilical artery Doppler studies was selected. All placentas were inspected for evidence of underperfusion and classified in accordance with established histologic criteria. Neurodevelopmental outcomes at 24 months (age-corrected) were then evaluated, applying the Bayley Scale for Infant and Toddler Development, Third Edition (Bayley-III) to assess cognitive, language, and motor competencies. The impact of PUP on each domain was measured via analysis of covariance, logistic and ordinal regression, with adjustment for smoking, socioeconomic status, gestational age at birth, gender, and breastfeeding. ResultsA total of 83 near-term SGA deliveries were studied, 46 (55.4%) of which showed signs of PUP. At 2 years, adjusted neurodevelopmental outcomes were significantly poorer in births involving PUP (relative to SGA infants without PUP) for all three domains of the Bayley scale: cognitive (105.5 vs 96.3, adjusted-p = 0.03), language (98.6 vs 87.8, adjusted-p<0.001), and motor (102.7 vs 94.5, adjusted-p = 0.007). Similarly, the adjusted likelihood of abnormal cognitive, language, and motor competencies in instances of underperfusion was 9.3-, 17.5-, and 1.44-fold higher, respectively, differing significantly for the former two domains. ConclusionsIn a substantial fraction of near-term SGA babies without Doppler evidence of placental insufficiency, histologic changes compatible with PUP are still identifiable. These infants are at greater risk of abnormal neurodevelopmental outcomes at 2 years.

Metabolomic Profile of Umbilical Cord Blood Plasma from Early and Late Intrauterine Growth Restricted (IUGR) Neonates with and without Signs of Brain Vasodilation

ObjectivesTo characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR).Methods23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10th centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10th centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10th centile. 1H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data. ResultsThe NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR.ConclusionsIUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.

Evaluation of an Optimal Gestational Age Cut-Off for the Definition of Early- and Late-Onset Fetal Growth Restriction

Objective: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. Patients and Methods: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). Results: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. Conclusions: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency

ObjectivesTo describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. MethodsA series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. ResultsA total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). DiscussionIn most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. ConclusionsA significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.

Prenatal diagnosis, clinical outcomes, and associated pathology in pregnancies complicated by massive subchorionic thrombohematoma (Breus' mole)

To review the association between ultrasound findings, placental pathology, and prognosis in pregnancies complicated by massive subchorionic thrombohematoma (MTH)/Breus' mole. We identified 14 cases of MTH from January 2004 to December 2012. MTH was defined by >1 cm thickness hematoma and extensive (≥50%) involvement of the fetal surface of the placenta. Patient information, details of initial presentation, and perinatal outcome were obtained from the manual and electronic chart records. Ultrasound findings were related to pregnancy outcomes and associated placental pathology. Participants were stratified on the basis of birth outcome into survivors (live births, n = 7) and nonsurvivors (neonatal deaths or intrauterine fetal deaths/termination of pregnancy, n = 7). All 14 cases of MTH were suspected on ultrasound and confirmed by pathology assessment. All cases in the nonsurvivor group had abnormal umbilical artery (UA) Doppler waveforms compared with none in the survivors (p = 0.02). All cases in the nonsurvivor group had extreme preterm deliveries (p = 0.02). Birth weight was significantly reduced in the nonsurvivor group (p = 0.001), and 5/7 cases were diagnosed with severe intrauterine growth restriction, compared with none in the survivor group (p = 0.02). Massive subchorionic thrombohematoma/Breus' mole may be diagnosed in the second trimester by ultrasound assessment of the placenta. Normal fetal growth and UA Doppler waveforms are associated with perinatal survival.