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.

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.

The customized fetal growth potential: a standard for Ireland.

OBJECTIVE: To identify maternal and pregnancy-related physiological and pathological variables associated with fetal growth and birthweight in Ireland and to develop customized birthweight centile charts for the Irish population that will aid in appropriate identification and selection of growth-restricted fetuses requiring increased antenatal surveillance. STUDY DESIGN: Prospectively collected outcome data of 11,973 consecutive ultrasound-dated singleton pregnancies between 2008 and 2009 from six maternity units in Ireland (Dublin, Galway, Limerick and Belfast) were included for analysis. Maternal weight and height at booking, parity and ethnicity were recorded and combined with birthweight, fetal gender and pregnancy outcomes. Coefficients were derived by backward multiple regression using a stepwise backward elimination approach. RESULTS: A total of 11,973 ultrasound-dated singleton pregnancies were included in the analysis. Over 90% of women (n=10,850) were of Irish or European descent, 3.4% (n=407) were African or African Caribbean, 1.7% (n=208) were Indian; 42.2% (n=5057) were nulliparous, 32.8% (n=3923) had one previous delivery after 24 weeks' gestation, 15.6% (n=1872) had two previous deliveries and 9.4% (n=1121) had three or more previous deliveries. Mean term birthweight for a standard Irish mother was 3491 grams. Babies of all other ethnic origins were smaller than their Irish counterparts. African Caribbean, Bangladeshi, Indian and Pakistani babies were on average 237 g, 196 g, 181 g and 181 g lighter, respectively, when compared to the average Irish offspring. Pathological factors significantly affecting term birthweight were pre-gestational diabetes (+137 g; p<0.001), smoking (-225 g; p<0.001), pregnancy-induced hypertension (-37.6g; p=0.009) and maternal obesity (-41.6g; p=0.012). CONCLUSION: Birthweight in this Irish maternity population is subject to similar influences to those observed in studies from the UK, Sweden, USA and Australasia. The derived coefficients can be used for customized assessment of fetal growth potential in Ireland. The implementation of these customized centile charts and their free online availability will aid clinicians in Ireland in the interpretation of fetal weight estimation.

Correlation between maternal inflammatory markers and fetomaternal adiposity.

Outside pregnancy, both obesity and diabetes mellitus are associated with changes in inflammatory cytokines. Obesity in pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or fetal macrosomia. The objective of this study was to determine the correlation between maternal cytokines and fetomaternal adiposity in the third trimester in women where the important confounding variable GDM had been excluded. Healthy women with a singleton pregnancy and a normal glucose tolerance test at 28 weeks gestation were enrolled at their convenience. Maternal cytokines were measured at 28 and 37 weeks gestation. Maternal adiposity was assessed indirectly by calculating the Body Mass Index (BMI), and directly by bioelectrical impedance analysis. Fetal adiposity was assessed by ultrasound measurement of fetal soft tissue markers and by birthweight at delivery. Of the 71 women studied, the mean maternal age and BMI were 29.1 years and 29.2 kg/m(2) respectively. Of the women studied 32 (45%) were obese. Of the cytokines, only maternal IL-6 and IL-8 correlated with maternal adiposity. Maternal TNF-α, IL-ß, IL-6 and IL-8 levels did not correlate with either fetal body adiposity or birthweight. In this well characterised cohort of pregnant non-diabetic women in the third trimester of pregnancy we found that circulating maternal cytokines are associated with maternal adiposity but not with fetal adiposity.

A clinical algorithm of prenatal diagnosis of Radial Ray Defects with two and three dimensional ultrasound.

OBJECTIVE: To review the antenatal diagnosis of Radial Ray Defects (RRD) in a tertiary referral fetal medicine unit & to set out a clinical algorithm to aid assessment and management. METHODS: All cases of RRD isolated or associated with other anomalies notified to NorCAS between 2000 and 2005 were identified. Outcome information was obtained from paediatric records and histopathology and cytogenetics in cases of pregnancy interruption. RESULTS: Thirty five cases were referred, 17 cases were excluded including skeletal dysplasia (16). An antenatal diagnosis was made in 61% (11/18) - isolated limb reduction defects, Trisomy 18, TAR, fetal valproate syndrome, Roberts syndrome. Of the rest, 3 had a cordocentesis with normal chromosome fragility tests (VACTERL association, Goldenhar syndrome and Acrofacial dysostosis) and 4 declined testing (2 TOP with Cornelia de Lange, 2 ongoing pregnancies diagnosed postpartum with Fanconi anaemia and VACTERL association). CONCLUSIONS: The challenge of radial ray anomalies is to combine clinical and ultrasound expertise with input from clinical genetics, ultrasound and molecular testing. Our clinical algorithm encourages targeted sonography including 3D views for subtle face, ear and hand anomalies, providing a useful tool to diagnose the underlying condition, crucial for appropriate obstetric management and prognosticating for future pregnancies.