Spontaneous Human Myometrial Contractility in the Third Trimester of Pregnancy in Relation to Past Mode of Delivery.

OBJECTIVE: It is well established that women with a previous vaginal delivery have higher success rates in relation to vaginal birth after cesarean than those without. The aim of this study was to examine the effect of past mode of delivery on contractile parameters of human myometrium in vitro. STUDY DESIGN: Myometrial strips were excised from 64 women at cesarean delivery (CD) and recordings of spontaneous contractile activity analyzed and compared across three clinical groups: (1) women with no previous delivery (Group 1); (2) women with CD only (Group 2); and (3) women with a history of vaginal delivery and CD (Group 3). RESULTS: Myometrial samples from women in Group 3, women who had a previous vaginal delivery, had a significantly greater maximum amplitude of contractions (p < 0.05), a greater force (mean contractile force) of contractions (p < 0.01), and a faster rate of rise (p < 0.01) and relaxation of contractions (p < 0.05) than those in Groups 1 and 2. CONCLUSION: Many of the functional parameters of human uterine contractions are altered, or enhanced, in the women who have had a previous vaginal delivery, when compared with those without. This may partly explain the clinical differences observed in labor.

Emerging and legacy brominated flame retardants in the breast milk of first time Irish mothers suggest positive response to restrictions on use of HBCDD and Penta- and Octa-BDE formulations.

The brominated flame retardants (BFRs) hexabromocyclododecane (HBCDD), eight polybrominated diphenyl ethers (PBDEs), and decabromodiphenyl ethane (DBDPE) were measured in 16 pools of human milk from Ireland. Concentrations of BDEs-47, -99, -100, -153, and HBCDD were significantly lower (p < 0.05) than those in Irish human milk collected in 2011. In contrast, concentrations of BDE-209 in our study exceeded those in 2011, and while decabromodiphenyl ethane (DBDPE) was not detected in 2011 it was detected in 3 of our samples. This suggests increased use of DBDPE and that while restrictions on the Penta- and Octa-BDE formulations are reducing human exposure, those on Deca-BDE use have yet to reduce body burdens. Estimated exposures for nursing infants to all target BFRs do not suggest a health concern. A one compartment pharmacokinetic model was used to predict body burdens arising from BFR intakes via air, dust and diet. While for most targeted BFRs, predicted and observed body burdens derived from our human milk data compared reasonably well; predicted BDE-209 and DBDPE values were substantially lower than observed. This suggests exposure pathways not included in the model like dermal uptake from fabrics may be important, and highlights knowledge gaps about the human half-lives and bioavailability of these contaminants.

The Impact of Aspirin on Ultrasound Markers of Uteroplacental Flow in Low-Risk Pregnancy: Secondary Analysis of a Multicenter RCT.

OBJECTIVE: This article evaluates the effect of low-dose aspirin on uterine artery (UtA) Doppler, placental volume, and vascularization flow indices in low-risk pregnancy. STUDY DESIGN: In this secondary analysis of the TEST randomized controlled trial, low-risk nulliparous women were originally randomized at 11 weeks to: (1) routine aspirin 75 mg; (2) no aspirin; and (3) aspirin based upon the preeclampsia Fetal Medicine Foundation screening test. UtA Doppler, three-dimensional (3D) placental volume, and vascularization flow indices were assessed prior to and 6 weeks postaspirin commencement. RESULTS: A total of 546 women were included (aspirin n = 192, no aspirin n = 354). Between first and second trimesters, aspirin use was not associated with a change in UtA Doppler, placental volume, or vascular flow indices. There was no significant difference in the change in UtA Doppler pulsatility index (PI) Z-scores or notching (PI Z-score -0.2 vs. -0.2, p = 0.17), nor was there a significant change in placental volume Z-score and vascular flow indices (volume Z-score change: 0.74 vs. 0.62, p = 0.34). CONCLUSION: Low-dose aspirin commenced at 11 weeks in low-risk women does not appear to improve uterine and placental perfusion or placental volume. Any perceived effect on uteroplacental vasculature is not reflected in changes in placental volume nor uteroplacental flow as assessed by two-dimensional and 3D ultrasound.

Comment on: Synthesis of New Azo Compounds Based on N-(4-Hydroxyphenyl)maleimide and N-(4-Methylphenyl)maleimide. Molecules 2010, 15, 7498-7508.

The synthesis of (E)-phenylazo-3-N-(4-hydroxyphenyl)maleimide (1) using a procedure previously reported in Molecules is deemed to be erroneous. A detailed re-investigation of the earlier work suggests that the spectral data for key intermediates and the final product, (1), was mis-assigned. We conclude that compound (1) was not synthesized, but rather an unusual ring opening reaction of the maleimide unit of the starting material, N-(4-hydroxyphenyl)maleimide (2) leading to the generation of (Z)-4-((4-hydroxyphenyl)amino)-4-oxobut-2-enoic acid, (3) was observed instead. Examination of the original experimental data reveals systematic errors in the reporting of all of the combustion microanalytical data. Overall, the present investigation suggests that errors in the interpretation of spectral data, falsification of analytical data and selective editing of experimental results raise questions over the veracity of the work presented in the original paper.

Prediction of cesarean delivery in the term nulliparous woman: results from the prospective, multicenter Genesis study.

BACKGROUND: In contemporary practice many nulliparous women require intervention during childbirth such as operative vaginal delivery or cesarean delivery (CD). Despite the knowledge that the increasing rate of CD is associated with increasing maternal age, obesity and larger infant birthweight, we lack a reliable method to predict the requirement for such potentially hazardous obstetric procedures during labor and delivery. This issue is important, as there are greater rates of morbidity and mortality associated with unplanned CD performed in labor compared with scheduled CDs. A prediction algorithm to identify women at risk of an unplanned CD could help reduced labor associated morbidity. OBJECTIVE: In this primary analysis of the Genesis study, our objective was to prospectively assess the use of prenatally determined, maternal and fetal, anthropomorphic, clinical, and ultrasound features to develop a predictive tool for unplanned CD in the term nulliparous woman, before the onset of labor. MATERIALS AND METHODS: The Genesis study recruited 2336 nulliparous women with a vertex presentation between 39+0 and 40+6 weeks' gestation in a prospective multicenter national study to examine predictors of CD. At recruitment, a detailed clinical evaluation and ultrasound assessment were performed. To reduce bias from knowledge of these data potentially influencing mode of delivery, women, midwives, and obstetricians were blinded to the ultrasound data. All hypothetical prenatal risk factors for unplanned CD were assessed as a composite. Multiple logistic regression analysis and mathematical modeling was used to develop a risk evaluation tool for CD in nulliparous women. Continuous predictors were standardized using z scores. RESULTS: From a total enrolled cohort of 2336 nulliparous participants, 491 (21%) had an unplanned CD. Five parameters were determined to be the best combined predictors of CD. These were advancing maternal age (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09 to 1.34), shorter maternal height (OR, 1.72; 95% CI, 1.52 to 1.93), increasing body mass index (OR, 1.29; 95% CI, 1.17 to 1.43), larger fetal abdominal circumference (OR, 1.23; 95% CI, 1.1 to 1.38), and larger fetal head circumference (OR, 1.27; 95% CI, 1.14 to 1.42). A nomogram was developed to provide an individualized risk assessment to predict CD in clinical practice, with excellent calibration and discriminative ability (Kolmogorov-Smirnov, D statistic, 0.29; 95% CI, 0.28 to 0.30) with a misclassification rate of 0.21 (95% CI, 0.19 to 0.25). CONCLUSION: Five parameters (maternal age, body mass index, height, fetal abdominal circumference, and fetal head circumference) can, in combination, be used to better determine the overall risk of CD in nulliparous women at term. A risk score can be used to inform women of their individualized probability of CD. This risk tool may be useful for reassuring most women regarding their likely success at achieving an uncomplicated vaginal delivery as well as selecting those patients with such a high risk for CD that they should avoid a trial of labor. Such a risk tool has the potential to greatly improve planning hospital service needs and minimizing patient risk.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

BACKGROUND: Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. OBJECTIVE: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. STUDY DESIGN: In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. RESULTS: Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). CONCLUSION: The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.

Prenatal prediction of significant intertwin birthweight discordance using standard second and third trimester sonographic parameters.

INTRODUCTION: Our study aim was to evaluate standard ultrasound-derived fetal biometric parameters in the prediction of clinically significant intertwin birthweight discordance defined as ≥18%. MATERIAL AND METHODS: This was a secondary analysis of a prospective cohort study of 1028 unselected twin pairs recruited over a two-year period. Dichorionic twins underwent two-weekly ultrasonographic surveillance from 24 weeks' gestation, with surveillance of monochorionic twins two-weekly from 16 weeks. Ultrasonographic biometric data from 24 to 36 weeks were evaluated for the prediction of an intertwin birthweight discordance threshold ≥18%. Umbilical artery Doppler waveform data was also analyzed to evaluate whether it was predictive of birthweight discordance. RESULTS: Of the 956 twin pairs analyzed for discordance, 208 pairs were found to have a clinically significant birthweight discordance ≥18%. All biometric parameters were predictive of significant inter-twin birthweight discordance at low cut-offs, with low discriminatory powers when ROC curves were analyzed. Discordance in estimated fetal weight was predictive of a significant birthweight discordance at all gestational categories with cut-offs between 8 and 11%. A low-discriminatory power and poor sensitivity and specificity were also observed. An abnormal umbilical artery Doppler was predictive of birthweight discordance ≥18% between 28 and 32 weeks' gestation, although with poor sensitivity and specificity. CONCLUSIONS: Calculation of estimated fetal weight and birthweight discordance between twins allows minimal margin for error. These margins make it difficult to accurately predict those who are at or above the discordance threshold of 18%. These findings highlight that small intertwin discrepancies in weight and biometry should not be overlooked and merit further investigation.

Neuro-developmental outcome of a large cohort of growth discordant twins.

UNLABELLED: Our aims were to study the effect of birthweight growth discordance (≥20%) on neuro-developmental outcome of monochorionic and dichorionic twins and to compare the relative effects of foetal growth discordance and prematurity on cognitive outcome. We performed a cross-sectional multicentre prospective follow-up study from a cohort of 948 twin pregnancies. One hundred nineteen birthweight-discordant twin pairs were examined (24 monochorionic pairs) and were matched for gestational age at delivery with 111 concordant control pairs. Participants were assessed with the Bayley Scales between 24 and 42 months of age. Analysis was by paired t test for intra-twin pair differences and by multiple linear regression. Compared to the larger twin of a discordant pair, the smaller twin performed significantly worse in cognition (mean composite cognitive score difference = -1.7, 95% confidence interval (CI) = 0.3-3.1, p = 0.01) and also in language and motor skills. Prematurity prior to 33 weeks' gestation, however, had a far greater impact on cognitive outcomes (mean cognitive composite score difference = -5.8, 95% CI = 1.2-10.5, p = 0.008). CONCLUSION: Birthweight growth discordance of ≥20% confers an independent adverse effect on long-term neuro-development of the smaller twin. However, prior to 33 weeks' gestation, gestational age at birth adversely affects cognitive development to a greater extent than foetal growth discordance.

Paeoniflorin, a novel heat-shock protein inducing compound, and human myometrial contractility in vitro.

AIM: Heat shock proteins (HSPs) are synthesized in virtually all organisms in response to increases in temperature. They are associated with a relaxant effect on the human myometrium and are present in decreased concentration in the myometrium at the time of labor. Paeoniflorin is derived from Paeonia lactiflora and has been shown to induce the synthesis of HSPs in cultured mammalian cells. The purpose of the study was to evaluate the effect of paeoniflorin on human uterine contractility. MATERIAL AND METHODS: Samples of human myometrium were taken at lower segment cesarean section. Dissected muscle strips were suspended under isometric conditions and exposed to cumulative additions of paeoniflorin in concentrations ranging from 1 nmol/L to 10 mol/L. Control experiments were simultaneously performed. RESULTS: Paeoniflorin was found to exert an inhibitory effect on spontaneous and agonist-induced contractions compared to control strips. The mean maximal inhibition values were: 42.21% ± 9.26 for spontaneous contractions (n = 6; P < 0.0001) and 47.84% ± 9.05 for oxytocin-induced contractions (n = 6; P < 0.0001). CONCLUSION: The HSP inducing compound, paeoniflorin, had a relaxant effect on human uterine contractility in vitro. These results reinforce the fact that HSPs may play a physiological role in the onset of labor and may also provide future targets for novel tocolytic treatments.

Gestational hypertensive disease in twin pregnancy: Influence on outcomes in a large national prospective cohort.

OBJECTIVE: Gestational hypertensive disease (GHD) is associated with pregnancy-related complications and poor maternal and fetal outcomes in singleton pregnancies. We sought to examine the influence of GHD in a large prospective cohort of twin pregnancies. STUDY DESIGN: The ESPRIT study was a national multicenter observational cohort study of 1028 structurally normal twin pregnancies. Each pregnancy underwent sonographic surveillance with two-week ultrasound from 24 weeks for dichorionic and from 16 weeks for monochorionic gestations. Characteristics and demographics as well as labour and delivery outcome data were prospectively recorded. Perinatal mortality, admission to the neonatal intensive care unit (NICU) and a composite of morbidity of respiratory distress syndrome, hypoxic ischaemic encephalopathy, periventricular leukomalacia, necrotising enterocolitis and sepsis were documented for all cases. Outcomes for patients with documented GHD (pre-eclampsia and gestational hypertension) were compared with those without GHD. RESULTS: Perinatal outcome data were recorded for 977 patients. Women with GHD had a higher body mass index (27.1 ± 6.4 vs 25.2 ± 4.5, P < 0.0001) than those without and were more likely to be nulliparous (65% (59/92) vs 46% (407/885), P = 0.001). Both groups had similar mean birthweights, but those with GHD were more likely to have a birthweight discordance ≥18% (35% (32/92) vs 20% (179/885), P = 0.001). Rates of caesarean delivery were higher in those twin pregnancies affected by GHD, and while the rate of composite morbidity was similar in both groups, twins in the GHD group had higher rates of NICU admission. CONCLUSION: In twin gestations, gestational hypertension independently confers an increased risk for emergency caesarean delivery, birthweight discordance and NICU admission, such that intensive maternal-fetal monitoring is justified when hypertension develops in a twin pregnancy.

The effect of maternal obesity on sonographic fetal weight estimation and perinatal outcome in pregnancies complicated by fetal growth restriction.

PURPOSE: Maternal obesity represents a challenge in the sonographic (US) assessment of fetal weight, and is a recognized risk factor for adverse pregnancy outcome. The objective of this secondary analysis of data from the Prospective Observational Trial to Optimize Pediatric Health in fetal growth restriction (FGR) Study (PORTO) was to describe the effect of maternal obesity on the accuracy of US in determining the estimated fetal weight (EFW) and the perinatal outcome of pregnancies affected by FGR. METHODS: Between 2010 and 2012, 1,116 women with nonanomalous singleton pregnancies with an EFW in less than the tenth centile were recruited for the PORTO study. Maternal body mass index (BMI) was divided into five subcategories: normal (BMI < 24.9 kg/m(2) ), overweight (25-29.9), obese class 1 (30-34.9), obese class 2 (35-39.9), and obese class 3 (>40). The accuracy of the EFW was determined in women who delivered within 2 weeks of their last US scan. Perinatal outcomes were analyzed by BMI subcategory. RESULTS: Of the 1,074 patients with complete records, 691 (64%) were of normal weight, 258 (24%) were overweight, 93 (9%) were in obese class 1, 32 (3%) were in obese class 2, and none were in obese class 3. Overall, the EFW determined prior to delivery was within 6% of the actual birth weight in all BMI subcategories. Overweight and obese women delivered more commonly by cesarean section and at earlier gestational ages than did women with a normal BMI (p = 0.0008), resulting in lower birth weights (p = 0.0031) and significantly increased composite perinatal morbidity (p < 0.0001) and mortality (p = 0.0215) rates. CONCLUSIONS: US examination is reliable for assessing the weight of fetuses with FGR in overweight women. Maternal obesity, however, has a significant adverse effect on perinatal outcomes. Thus, health education should focus on awareness of this adverse effect, with optimization of prepregnancy weight as its main goal.

Natural history of fetal trisomy 13 after prenatal diagnosis.

There are currently limited data describing the natural history and outcome for fetal trisomy 13 diagnosed prenatally. The aim of this study was to evaluate the fetal and neonatal outcome for pregnancies with an established prenatal diagnosis of fetal trisomy 13, and a parental decision for continuation of the pregnancy. To this end, the obstetric and neonatal outcome data for such pregnancies, diagnosed at two referral Fetal Medicine Centers, were retrospectively obtained and examined. During the study period, there were 45 cases of trisomy 13 diagnosed at both units, of which 26 (56%) continued with the pregnancy to its natural outcome. There were 12 intrauterine deaths in the cohort resulting in a rate of 46.2% of intrauterine lethality. Conversely, the live birth rate was 53.8%. For infants born alive, neonatal death on day 1 of life occurred in 78.6% of cases. The overall early neonatal mortality rate was 93%. There was one infant death at 6 weeks of age and no survival noted beyond this period. These data provide reliable information for parental counseling pertaining to risk of intrauterine death when trisomy 13 is diagnosed prenatally. These data also indicate that the survival outcome is worse than that previously accepted from studies of postnatal follow up of live born infants with this diagnosis.

Dichorionic twin ultrasound surveillance: sonography every 4 weeks significantly underperforms sonography every 2 weeks: results of the Prospective Multicenter ESPRiT Study.

OBJECTIVE: A 2-week ultrasound scanning schedule for monochorionic twins is endorsed widely. There is a lack of robust data to inform a schedule for the surveillance of dichorionic gestations. We aimed to determine how ultrasound scanning that is performed at 2- or 4-week intervals (or every 4 weeks before 32 weeks' gestation and every 2 weeks thereafter) may impact the prenatal detection of fetal growth restriction (FGR) and ultimately influence timing of delivery. STUDY DESIGN: In a consecutive cohort of 789 dichorionic twin pregnancies that were recruited prospectively for the multicenter Evaluation of Sonographic Predictors of Restricted Growth in Twins study, ultrasound determination of fetal growth and interrogation of umbilical and middle cerebral artery Doppler scans were performed every 2 weeks from 24 weeks' gestation until delivery. Complete delivery and perinatal outcome data were recorded for all pregnancies. Where delivery was prompted by FGR, abnormal umbilical artery Doppler examination or poor biophysical profile and in the absence of ruptured membranes, onset of labor, preeclampsia, or antepartum hemorrhage, the delivery was considered "ultrasound-indicated." For ultrasound-indicated deliveries, detection probabilities for FGR/abnormal umbilical artery Doppler scans/poor biophysical were determined according to the interval between examinations, by the suppression if alternate examination data. RESULTS: Among 789 dichorionic twin pregnancies, 66 pairs (8%) had an "ultrasound indicated" delivery. Detection of FGR was reduced from 88-69%, and detection of abnormal umbilical artery Doppler was reduced from 82-62% when a 4-week ultrasound schedule was simulated. Both of these reductions reached statistical significance. There was a nonsignificant trend toward a reduction in the recording of oligohydramnios with a 4-week interval between examinations. CONCLUSION: This study suggests that the ultrasound surveillance program of every 2 weeks that is recommended currently for monochorionic twins should be extended to dichorionic gestations.

Human uterine lower segment myometrial cell and nuclear volume at term: influence of maternal age.

Little is known about the cytoarchitecture of human myometrial cells in pregnancy, and whether or not this may be influenced by maternal characteristics such as age, parity and body mass index (BMI). The aim of this study was primarily to evaluate human myometrial smooth muscle cell (SMC) and nuclear volume in the third trimester of human pregnancy, and secondarily to investigate if these parameters are altered in relation to the maternal characteristics outlined above. Myometrial biopsies were obtained from 30 women undergoing elective caesarean delivery at term. One-micrometer sections were prepared for light microscopy and 100-nm sections for electron microscopy. The nucleator technique was used to assess nuclear volume from the light microscopy images. Point-counting methodology was used on transmission electron micrographs to assess the percentage of the cell volume occupied by the nucleus. Cell volume was calculated from these measurements. The euchromatin to heterochromatin (Eu/Het) ratio was determined to ascertain whether differences in nuclear volume were due to an increased range of genes being transcribed. The mean (±â€…SEM) nuclear volume was 175 ±â€…10 µm(3) , the nucleus occupied 1.5 ±â€…0.1% of the SMC and the mean cell size was 14 047 ±â€…1352 µm(3) . The Eu/Het ratio was 7.54 ±â€…0.4. The mean volume of heterochromatin and euchromatin in the nucleus was 21.5 ±â€…1.7 and 149 ±â€…9 µm(3) , respectively. A multivariate regression analysis revealed that advanced maternal age was associated with an increase in the percentage of the cell occupied by nucleus (R(2)  = 0.32, P = 0.004). There were no other significant effects of maternal age, BMI or parity on the measured parameters. These findings provide reliable volumes for human myometrial cells and their nuclei at term gestation, and show that nuclear volume fraction may be influenced by maternal age.

The influence of maternal body mass index on fetal weight estimation in twin pregnancy.

OBJECTIVE: Sonographic estimated fetal weight (EFW) is important in the management of high-risk pregnancies. The possibility that increased maternal body mass index (BMI) adversely affects EFW assessments in twin pregnancies is controversial. The aim of this study was to investigate the effect of maternal BMI on the accuracy of EFW assessments in twin gestations prospectively recruited for the ESPRiT (Evaluation of Sonographic Predictors of Restricted growth in Twins) study. STUDY DESIGN: One thousand one twin pair pregnancies were recruited. After exclusion, BMI, birthweights, and ultrasound determination of EFW (within 2 weeks of delivery) were available for 943 twin pairs. The accuracy of EFW determination was defined as the difference between EFW and actual birthweight for either twin (absolute difference and percent difference). Cells with less than 5% of the population were combined for analysis resulting in the following 3 maternal categories: (1) normal/underweight, (2) overweight, and (3) obese/extremely obese. RESULTS: Analysis of the 3 categories revealed mean absolute variation values of 184 g (8.0%) in the normal/underweight group (n = 531), 196 g (8.5%) in the overweight group (n = 278), and 206 g (8.6%) in the obese/extremely obese group (n = 134) (P = .028, which was nonsignificant after adjustment for multiple testing). Regression analysis showed no linear or log-linear relationship between BMI and the accuracy of EFW (P value for absolute difference = .11, P value for percentage difference = .27). CONCLUSION: Contrary to a commonly held clinical impression, increasing maternal BMI has no significant impact on the accuracy of EFW in twin pregnancy.

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

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

The role of brain sparing in the prediction of adverse outcomes in intrauterine growth restriction: results of the multicenter PORTO Study.

OBJECTIVE: The aim of the Prospective Observational Trial to Optimize Pediatric Health in IUGR Study was to evaluate the optimal management of fetuses with an estimated fetal weight less than the 10th centile. The objective of this secondary analysis was to describe the role of the cerebroplacental ratio (CPR) in the prediction of adverse perinatal outcome. STUDY DESIGN: More than 1100 consecutive singleton pregnancies with intrauterine growth restriction (IUGR) were recruited over 2 years at 7 centers, undergoing serial sonographic evaluation including multivessel Doppler measurement. CPR was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. RESULTS: Data for CPR calculation was available in 881 cases, which was performed at a mean gestational age of 33 weeks (interquarile range, 28.7-35.9). Of the 146 cases with CPR less than 1, 18% (n = 27) had an adverse perinatal outcome. This conferred an 11-fold increased risk (odds ratio, 11.7; P < .0001) when compared with cases with normal CPR (2%; 14 of 735). An abnormal CPR was present in all 3 cases of mortality. Prediction of adverse outcomes was comparable when using all definitions of abnormal CPR. CONCLUSION: Irrespective of the CPR calculation used, brain sparing is significantly associated with an adverse perinatal outcome in IUGR. This adds further weight to integrating CPR evaluation into the clinical assessment of IUGR pregnancies. The impact of this finding on long-term neurodevelopmental outcomes in this patient cohort is underway.

Evaluation of imaging quality of pulmonary 64-MDCT angiography in pregnancy and puerperium.

OBJECTIVE: The aim of this study was to quantitatively and qualitatively evaluate pulmonary 64-MDCT angiography image quality in pregnancy and puerperium, compared with female nonpregnant control subjects. MATERIALS AND METHODS: The study group comprised 124 consecutive pregnant and postpartum women and 124 female nonpregnant control subjects who presented with suspected pulmonary embolism. The individual studies were evaluated for subjective and objective diagnostic quality. RESULTS: Objective measurements of the arterial enhancement in the pulmonary trunk and left and right pulmonary arteries found that there was no statistically significant difference in attenuation values between the pregnant and puerperium group and the control group for pulmonary artery opacification. The mean attenuation in the pulmonary trunk was 270.54 HU in the pregnant group, 277.53 HU in the puerperium group, and 293.90 HU in the control group. CONCLUSION: We found no significant difference in diagnostic quality of pulmonary CT angiography using MDCT between the study and control groups. The use of MDCT acquisition, faster injection rates, higher contrast medium concentration, and higher trigger levels may decrease the number of nondiagnostic studies in this population. MDCT may be a worthwhile investigation in the majority of pregnant patients with suspected pulmonary embolism.

Fetal growth restriction and the risk of perinatal mortality-case studies from the multicentre PORTO study.

BACKGROUND: Intrauterine growth restriction (IUGR) is the single largest contributing factor to perinatal mortality in non-anomalous fetuses. Advances in antenatal and neonatal critical care have resulted in a reduction in neonatal deaths over the past decades, while stillbirth rates have remained unchanged. Antenatal detection rates of fetal growth failure are low, and these pregnancies carry a high risk of perinatal death. METHODS: The Prospective Observational Trial to Optimize Paediatric Health in IUGR (PORTO) Study recruited 1,200 ultrasound-dated singleton IUGR pregnancies, defined as EFW <10th centile, between 24+0 and 36+6 weeks gestation. All recruited fetuses underwent serial sonographic assessment of fetal weight and multi-vessel Doppler studies until birth. Perinatal outcomes were recorded for all pregnancies. Case records of the perinatal deaths from this prospectively recruited IUGR cohort were reviewed, their pregnancy details and outcome were analysed descriptively and compared to the entire cohort. RESULTS: Of 1,116 non-anomalous singleton infants with EFW <10th centile, 6 resulted in perinatal deaths including 3 stillbirths and 3 early neonatal deaths. Perinatal deaths occurred between 24+6 and 35+0 weeks gestation corresponding to birthweights ranging from 460 to 2260 grams. Perinatal deaths occurred more commonly in pregnancies with severe growth restriction (EFW <3rd centile) and associated abnormal Doppler findings resulting in earlier gestational ages at delivery and lower birthweights. All of the described pregnancies were complicated by either significant maternal comorbidities, e.g. hypertension, systemic lupus erythematosus (SLE) or diabetes, or poor obstetric histories, e.g. prior perinatal death, mid-trimester or recurrent pregnancy loss. Five of the 6 mortalities occurred in women of non-Irish ethnic backgrounds. All perinatal deaths showed abnormalities on placental histopathological evaluation. CONCLUSIONS: The PNMR in this cohort of prenatally identified IUGR cases was 5.4/1,000 and compares favourably to the overall national rate of 4.1/1,000 births, which can be attributed to increased surveillance and timely delivery. Despite antenatal recognition of IUGR and associated maternal risk factors, not all perinatal deaths can be prevented.