A Pilot Randomized Controlled Trial of Early Targeted Patent Ductus Arteriosus Treatment Using a Risk Based Severity Score (The PDA RCT).

OBJECTIVES: To evaluate the feasibility of recruiting preterm infants to a randomized controlled trial of patent ductus arteriosus (PDA) treatment based on a PDA severity score (PDAsc) and to characterize challenges in obtaining consent, compliance with the protocol, and PDA closure rates. STUDY DESIGN: This single-center, randomized control pilot study of 60 infants <29 weeks of gestation with a high PDAsc (≥5.0) at 36-48 hours of age receiving either ibuprofen or placebo intravenously. The study protocol did not allow for additional PDA therapy within the first 2 weeks. We reported the rate of consent, open label treatment, and PDA closure rates. The primary outcome was chronic lung disease or death. RESULTS: We approached 83 families for enrollment with 73 (88%) providing consent; 13 infants had a PDAsc of <5; of the remaining infants, 30 were assigned ibuprofen and 30 received placebo. Eight infants received open label treatment in the first 2 weeks (12%). The overall PDA closure rate after treatment was 57% in the intervention group and 17% in the control group (P < .01). There was no difference in the primary clinical outcome (OR, 0.8; 95% CI, 0.3-2.1). CONCLUSIONS: Using a PDAsc for infant recruitment to a PDA treatment randomized controlled trial is feasible. There is a high rate of consent and relatively low rate of open-label PDA treatment. The overall PDA closure rate in the intervention arm was low placing the emphasis on devising more effective PDA closure strategies in future randomized controlled trials. TRIAL REGISTRATION: ISRCTN (13281214) and European Union Drug Regulating Authorities Clinical Trials Database (2015-004526-33).

The RECIPE study: reducing emergency Caesareans and improving the Primiparous experience: a blinded, prospective, observational study.

BACKGROUND: The RECIPE study aims to validate a risk prediction model for intrapartum caesarean delivery which has been developed by our group. The Genesis study was a prospective observational study carried out by the Perinatal Ireland Research Consortium across 7 clinical centres in Ireland between October 2012 and June 2015. Genesis investigated a range of maternal and fetal parameters in a prospective blinded study of 2336 singleton pregnancies between 39 + 0-41 + 0 weeks' gestational age. This resulted in the development of a risk prediction model for Caesarean Delivery in nulliparous women at term. The RECIPE study now proposes to provide external validation of this risk prediction tool. METHODS: In order to externally validate the model, we aim to include a centre which was not involved in the original study. We propose a trial of risk-assignment for intrapartum caesarean amongst nulliparous women with a singleton pregnancy between 38 + 0 and 40 + 6 weeks' gestational age who are planning a vaginal birth. Results of the risk prediction tool will be concealed from participants and from midwives and doctors providing labour care.. Participants will be invited for an ultrasound scan and delivery details will be collated postnatally. The principal aim of this study is to externally validate the risk prediction model. This prediction model holds the potential to accurately identify nulliparous women who are likely to achieve an uncomplicated vaginal birth and those at high prospect of requiring an unplanned caesarean delivery. DISCUSSION: Validation of the Genesis prediction model would enable more accurate counselling for women in the antenatal setting regarding their own likelihood of requiring an intrapartum Caesarean section. It would also provide valuable personalised information to women about the anticipated course of their own labour. We believe that this is an issue of national relevance that will impact positively on obstetric practice, and will positively empower women to make considered, personalised choices surrounding labour and delivery.

An abnormal cerebroplacental ratio (CPR) is predictive of early childhood delayed neurodevelopment in the setting of fetal growth restriction.

BACKGROUND: Fetal growth restriction accounts for a significant proportion of perinatal morbidity and death. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the "at-risk" fetus in both fetal growth restriction and appropriate-for-gestational-age pregnancies. The Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction group has demonstrated previously that the presence of this "brain-sparing" effect is associated significantly with adverse perinatal outcomes in the fetal growth restriction cohort. However, data about neurodevelopment in children from pregnancies that are complicated by fetal growth restriction are sparse and conflicting. OBJECTIVE: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction NeuroDevelopmental Assessment Study was to determine whether children born after fetal growth-restricted pregnancies are at additional risk of adverse early childhood developmental outcomes compared with children born small for gestational age. The objective of this secondary analysis was to describe the role of cerebroplacental ratio in the prediction of adverse early childhood neurodevelopmental outcome. STUDY DESIGN: Participants were recruited prospectively from the Perinatal Ireland multicenter observational Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction study cohort. Fetal growth restriction was defined as birthweight <10th percentile with abnormal antenatal umbilical artery Doppler indices. Small for gestational age was defined similarly in the absence of abnormal Doppler indices. Cerebroplacental ratio was calculated with the pulsatility indices of the middle cerebral artery and divided by umbilical artery with an abnormal value <1. Children (n=375) were assessed at 3 years with the use of the Ages and Stages Questionnaire and the Bayley Scales of Infant and Toddler Development, 3rd edition. Small-for-gestational-age pregnancies with normal Doppler indices were compared with (1) fetal growth-restricted cases with abnormal umbilical artery Doppler and normal cerebroplacental ratio or (2) fetal growth restriction cases with both abnormal umbilical artery and cerebroplacental ratio. Statistical analysis was performed with statistical software via 2-sample t-test with Bonferroni adjustment, and a probability value of .00625 was considered significant. RESULTS: Assessments were performed on 198 small-for-gestational-age children, 136 fetal growth-restricted children with abnormal umbilical artery Doppler images and normal cerebroplacental ratio, and 41 fetal growth-restricted children with both abnormal umbilical artery Doppler and cerebroplacental ratio. At 3 years of age, although there were no differences in head circumference, children who also had an abnormal cerebroplacental ratio had persistently shorter stature (P=.005) and lower weight (P=.18). Children from fetal growth restriction-affected pregnancies demonstrated poorer neurodevelopmental outcome than their small-for-gestational-age counterparts. Fetal growth-restricted pregnancies with an abnormal cerebroplacental ratio had significantly poorer neurologic outcome at 3 years of age across all measured variables. CONCLUSION: We have demonstrated that growth-restricted pregnancies with a cerebroplacental ratio <1 have a significantly increased risk of delayed neurodevelopment at 3 years of age when compared with pregnancies with abnormal umbilical artery Doppler evidence alone. This study further substantiates the benefit of routine assessment of cerebroplacental ratio in fetal growth-restricted pregnancies and for counseling parents regarding the long-term outcome of affected infants.

A population survey of prevalence rates of antenatal depression in the Irish obstetric services using the Edinburgh Postnatal Depression Scale (EPDS).

Ireland has the second-highest birth rate in Europe and poorly developed perinatal psychiatry services. There are no screening services for antenatal depression and no data available on prevalence rates of depression among women attending the Irish obstetric services. The aim of this study was to assess the prevalence rates of depression during pregnancy in a population sample in Ireland using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. Pregnant women during all stages of pregnancy were recruited from five maternity hospitals throughout the Republic of Ireland. Approximately 5000 EPDS questionnaires were collected. Information on the participant's age, gestational week, gravidity, parity, and level of education attained was also collected. A score of > 12 was used as a measure of probable depression. Overall, 15.8% of pregnant women scored > 12 in the EPDS. There was a significant association between gestational week and rates of depression, with increasing rates occurring with advancing pregnancy (p < 0.001). Overall, higher socioeconomic groups were over-represented in the sample although we replicated the well-established findings of higher EPDS scores in women with lower educational attainment (p < 0.005). This study demonstrates that prevalence rates of probable antenatal depression are high among women attending the obstetric services in Ireland and highlight the importance of increasing awareness of antenatal depression. These high rates of antenatal depression may be related to certain conditions that are specific to an Irish setting: the absence of screening for depression in the context of grossly under-resourced perinatal psychiatry services. These findings provide indirect confirmatory evidence for the need for streamlined mental health services within reproductive health services.

Evaluation of the Effect of Low-Dose Aspirin on Biochemical and Biophysical Biomarkers for Placental Disease in Low-Risk Pregnancy: Secondary Analysis of a Multicenter RCT.

OBJECTIVE: To assess the effect of aspirin use in low-risk pregnancy on: (1) pregnancy-associated plasma protein-A (PAPP-A) and placental-like growth factor (PLGF); (2) urinary albumin-to-creatinine ratio (ACR) and blood pressure; (3) fetal growth parameters; and (4) placental histopathology. STUDY DESIGN: This secondary analysis from the T rial of low-dose aspirin with an E arly S creening T est for preeclampsia and growth restriction randomized controlled trial was based on low-risk nulliparous women randomized at 11 weeks to (1) aspirin 75 mg; (2) no aspirin; and (3) aspirin based on the preeclampsia Fetal Medicine Foundation screening test. At baseline, women underwent assessment of blood pressure, PAPP-A, PLGF, and ACR, repeated 9 to 10 weeks postaspirin, in addition to fetal growth assessment. Gross and histopathological placental analyses were performed in line with Amsterdam criteria. RESULTS: A total of 445 subjects were included (aspirin n = 163 [36.6%]; no aspirin n = 282 [63.4%]). Although the fetal-to-placental weight ratio was significantly greater in the aspirin group (7.5 [±1.3] vs. 7.3 [±1.4], p = 0.045), as was change in ultrasound assessed estimated fetal weight from second to third trimesters (1,624.5 g [±235.1] vs. 1,606.2 [±189.4], p = 0.042), this was invalidated by the lack of a difference in birth weight. Aspirin did not significantly impact on change in serum or urine preeclampsia biomarkers, maternal blood pressure, or placental histopathology. CONCLUSION: Aspirin use in low-risk pregnancy does not appear to impact on preeclampsia biomarkers, fetal growth, or placental pathology.

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.

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.

Altered Platelet Function in Intrauterine Growth Restriction: A Cause or a Consequence of Uteroplacental Disease?

Objective A limited number of platelet function studies in intrauterine growth restriction (IUGR) have yielded conflicting results. We sought to evaluate platelet reactivity in IUGR using a novel platelet aggregation assay. Study Design Pregnancies with IUGR were recruited from 24 weeks' gestation (estimated fetal weight < 10th centile) and had platelet function testing performed after diagnosis. A modification of light transmission aggregometry created dose-response curves of platelet reactivity in response to multiple agonists at differing concentrations. Findings were compared with healthy third trimester controls. IUGR cases with a subsequent normal birth weight were analyzed separately. Results In this study, 33 pregnancies retained their IUGR diagnosis at birth, demonstrating significantly reduced platelet reactivity in response to all agonists (arachidonic acid, adenosine diphosphate, collagen, thrombin receptor-activating peptide, and epinephrine) when compared with 36 healthy pregnancy controls (p < 0.0001). Similar results were obtained for cases demonstrating an increasing in utero growth trajectory. When IUGR preceded preeclampsia or gestational hypertension, platelet function was significantly reduced compared with normotensive IUGR. Conclusion Using this comprehensive platelet assay, we have demonstrated a functional impairment of platelets in IUGR. This may reflect platelet-derived placental growth factor release. Further evaluation of platelet function may aid in the development of future platelet-targeted therapies for uteroplacental disease.

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.

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.

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.

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.

Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study.

OBJECTIVE: The objective of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction (IUGR) (PORTO Study), a national prospective observational multicenter study, was to evaluate which sonographic findings were associated with perinatal morbidity and mortality in pregnancies affected by growth restriction, originally defined as estimated fetal weight (EFW) <10th centile. STUDY DESIGN: Over 1100 consecutive ultrasound-dated singleton pregnancies with EFW <10th centile were recruited from January 2010 through June 2012. A range of IUGR definitions were used, including EFW or abdominal circumference <10th, <5th, or <3rd centiles, with or without oligohydramnios and with or without abnormal umbilical arterial Doppler (pulsatility index >95th centile, absent or reversed end-diastolic flow). Adverse perinatal outcome, defined as a composite outcome of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death was documented for all cases. RESULTS: Of 1116 fetuses, 312 (28%) were admitted to neonatal intensive care unit and 58 (5.2%) were affected by adverse perinatal outcome including 8 mortalities (0.7%). The presence of abnormal umbilical Doppler was significantly associated with adverse outcome, irrespective of EFW or abdominal circumference measurement. The only sonographic weight-related definition consistently associated with adverse outcome was EFW <3rd centile (P = .0131); all mortalities had EFW <3rd centile. Presence of oligohydramnios was clinically important when combined with EFW <3rd centile (P = .0066). CONCLUSION: Abnormal umbilical artery Doppler and EFW <3rd centile were strongly and most consistently associated with adverse perinatal outcome. Our data call into question the current definitions of IUGR used. Future studies may address whether using stricter IUGR cutoffs comparing various definitions and management strategies has implications on resource allocation and pregnancy outcome.

Predictable progressive Doppler deterioration in IUGR: does it really exist?

OBJECTIVE: An objective of the Prospective Observational Trial to Optimize Pediatric Health in IUGR (PORTO) study was to evaluate multivessel Doppler changes in a large cohort of intrauterine growth restriction (IUGR) fetuses to establish whether a predictable progressive sequence of Doppler deterioration exists and to correlate these Doppler findings with respective perinatal outcomes. STUDY DESIGN: More than 1100 unselected consecutive ultrasound-dated singleton pregnancies with estimated fetal weight (EFW) less than the 10th centile were recruited between January 2010 and June 2012. Eligible pregnancies were assessed by serial Doppler interrogation of umbilical (UA) and middle cerebral (MCA) arteries, ductus venosus (DV), aortic isthmus, and myocardial performance index (MPI). Intervals between Doppler changes and patterns of deterioration were recorded and correlated with respective perinatal outcomes. RESULTS: Our study of 1116 nonanomalous fetuses comprised 7769 individual Doppler data points. Five hundred eleven patients (46%) had an abnormal UA, 300 (27%) had an abnormal MCA, and 129 (11%) had an abnormal DV Doppler. The classic pattern from abnormal UA to MCA to DV existed but no more frequently than any of the other potential pattern. Doppler interrogation of the UA and MCA remains the most useful and practical tool in identifying fetuses at risk of adverse perinatal outcome, capturing 88% of all adverse outcomes. CONCLUSION: In contrast to previous reports, we have demonstrated multiple potential patterns of Doppler deterioration in this large prospective cohort of IUGR pregnancies, which calls into question the usefulness of multivessel Doppler assessment to inform frequency of surveillance and timing of delivery of IUGR fetuses. These data will be critically important for planning any future intervention trials.