Elizabeth Tully

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.

The Role of Growth Trajectories in Classifying Fetal Growth Restriction

OBJECTIVE: To examine the validity of a growth trajectory method to discriminate between pathologically and constitutionally undergrown fetuses using repeated measures of estimated fetal weight. METHODS: In a prospective, observational, multicenter study in Ireland, 1,116 women with a growth-restricted fetus diagnosed participated with the objective of evaluating ultrasound findings as predictors of pediatric morbidity and mortality. Fetal growth trajectories were based on estimated fetal weight. RESULTS: Between 22 weeks of gestation and term, two fetal growth trajectories were identified: normal (96.7%) and pathologic (3.3%). Compared with the normal trajectory, the pathologic trajectory was associated with an increased risk for preeclampsia (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.6–23.4), increased umbilical artery resistance at 30 weeks of gestation (OR 12.6, 95% CI 4.6–34.1) or 34 weeks of gestation (OR 28.0, 95% CI 8.9–87.7), reduced middle cerebral artery resistance at 30 weeks of gestation (OR 0.33, 95% CI 0.12–0.96) or 34 weeks of gestation (OR 0.14, 95% CI 0.03–0.74), lower gestational age at delivery (mean 32.02 weeks of gestation compared with 38.02 weeks of gestation; P<.001), and higher perinatal complications (OR 21.5, 95% CI 10.5–44.2). In addition, 89.2% of newborns with pathologic fetal growth were admitted to neonatal intensive care units compared with 25.9% of those with normal growth. CONCLUSIONS: Fetal growth trajectory analysis reliably differentiated fetuses with a pathologic growth pattern among a group of women with growth-restricted fetuses. With further development, this approach could provide clarity to how we define, identify, and ultimately manage pathologic fetal growth. LEVEL OF EVIDENCE: II

Placental pathology, birthweight discordance, and growth restriction in twin pregnancy: results of the ESPRiT Study.

OBJECTIVE We sought to evaluate the association between placental histological abnormalities and birthweight discordance and growth restriction in twin pregnancies. STUDY DESIGN We performed a multicenter, prospective study of twin pregnancies. Placentas were examined for evidence of infarction, retroplacental hemorrhage, chorangioma, subchorial fibrin, or abnormal villus maturation. Association of placental lesions with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS In all, 668 twin pairs were studied, 21.1% monochorionic and 78.9% dichorionic. Histological abnormalities were more frequent in placentas of smaller twins of birthweight discordant pairs (P = .02) and in placentas of small for gestational age infants (P = .0001) when compared to controls. The association of placental abnormalities with both birthweight discordance and small for gestational age was significant for dichorionic twins (P = .01 and .0001, respectively). No such association was seen in monochorionic twins. CONCLUSION In a large, prospective, multicenter study, we observed a strong relationship between abnormalities of placental histology and birthweight discordance and growth restriction in dichorionic, but not monochorionic, twin pregnancies.

Comparison of outcomes of twins conceived spontaneously and by artificial reproductive therapy

Abstract Objective: To compare the outcomes of twin pregnancies conceived by artificial reproductive techniques (ART) with those of spontaneous conception. Study design: In this multicenter prospective trial, comparisons were made between methods of conception in twin pregnancies, for maternal and perinatal outcomes. Results: Of 1001 twin pairs, 763/1001 (72.7%) were spontaneously conceived and 238/1001(27.3%) were conceived by ART. There were no significant differences between the two groups with respect to obstetric complications. There were 13 per 1000 (20/1504; 1%) perinatal deaths in the spontaneously conceived group and 6 per 1000 (3/466; 0.6%) in the ART group (p = 0.8141). We found no differences in gestational age at delivery (median 36.9 versus 37.0 weeks), birth weight (median 2520 g versus 2538 g), or in a composite measure of adverse perinatal outcome (17% versus 15%) between the groups. Conclusion: There were no differences in the rate of adverse obstetric or perinatal outcomes between twins conceived naturally compared with twins conceived by assisted conception.

The Prenatal Distress Questionnaire: an investigation of factor structure in a high risk population

Background: The Prenatal Distress Questionnaire (PDQ) is a short measure designed to assess specific worries and concerns related to pregnancy. The aim of this study was to confirm the factor structure of the PDQ in a group of pregnant women with a small for gestational age infant (< 10th centile). Methods: The first PDQ assessment for each of 337 pregnant women participating in the Prospective Observational Trial to Optimise paediatric health (PORTO) study was analysed. All women enrolled in the study were identified as having a small for gestational age foetus (< 10th centile), thus representing an ‘elevated risk’ group. Data were analysed using confirmatory factor analysis (CFA). Three models of the PDQ were evaluated and compared in the current study: a theoretical uni-dimensional measurement model, a bi-dimensional model, and a three-factor model solution. Results: The three-factor model offered the best fit to the data while maintaining sound theoretical grounds(χ2 (51df) = 128.52; CFI = 0.97; TLI = 0.96; RMSEA = 0.07). Factor 1 contained items reflecting concerns about birth and the baby, factor 2 concerns about physical symptoms and body image and factor 3 concerns about emotions and relationships. Conclusions: CFA confirmed that the three-factor model provided the best fit, with the items in each factor reflecting the findings of an earlier exploratory data analysis.

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.

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

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.

An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol

OBJECTIVE Pre-eclampsia remains a worldwide cause of maternal and perinatal morbidity and mortality. Low dose aspirin (LDA) can reduce the occurrence of pre-eclampsia in women with identifiable risk factors. Emerging screening tests can determine the maternal risk of developing placental disease, such as pre-eclampsia from the first trimester of pregnancy. The aim of this study is to determine if it is more beneficial in terms of efficacy and acceptability to routinely prescribe LDA to nulliparous low-risk women compared to test indicated LDA on the basis of a positive screening test for placental disease. METHODS We propose a three armed multi-center open-labeled randomized control trial of; (i) routine LDA, (ii) no aspirin, and (iii) LDA on the basis of a positive first trimester pre-eclampsia screening test. LDA (75mg once daily) shall be given from the first trimester until 36-week gestation. The primary outcome measures include; (i) the proportion of eligible women that agree to participate (acceptability), (ii) compliance with study protocol (acceptability and feasibility), (iii) the proportion of women in whom it is possible to obtain first trimester trans-abdominal uterine artery Doppler examination (feasibility) and (iv) the proportion of women with a completed screening test that are issued the screening result within one week of having the test performed (feasibility). CONCLUSION This will be the first clinical trial to determine the efficacy and acceptability in low-risk women of taking routine LDA versus no aspirin versus LDA based on a positive first trimester screening test for the prevention of placental disease.

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

Our study aim was to evaluate standard ultrasound‐derived fetal biometric parameters in the prediction of clinically significant intertwin birthweight discordance defined as ≥18%.