Objective: This study explores the associations between lifestyle factors and late and moderate p... more Objective: This study explores the associations between lifestyle factors and late and moderate preterm birth (LMPT: 32+0-36+6 weeks gestation), a relatively under-researched group. Study design: A population based case-cohort study was undertaken involving 922 LMPT and 965 term (37+ weeks gestation) singleton live and stillbirths born between 01/09/2009-31/12/2010 to women residing in Leicestershire and Nottinghamshire, UK. Poisson multivariable regression models were fitted to estimate relative risks (RR) of LMPT birth associated with maternal smoking, alcohol and recreational drug use, and diet. Results: Women who smoked during pregnancy were at 38% increased risk of LMPT birth compared to non-smokers (RR 1.38 95% CI (1.04 to 1.84)). Low consumption of fruit and vegetables was associated with a 31% increased risk compared to those who reported eating higher consumption levels (RR 1.31 (1.03 to 1.66)). Women who did not have any aspects of a Mediterranean diet were nearly twice as likely to deliver LMPT compared to those whose diet included more Mediterranean characteristics (RR 1.81 (1.04 to 3.14)). Women who smoked and consumed low levels of fruit and vegetables (5%) were at particularly high risk (RR=1.81 (1.29 to 2.55)). There was no significant effect of alcohol or recreational drug use on LMPT birth. Conclusions: Smoking and poor diet during pregnancy, factors that strongly impact on very preterm birth, are also important at later gestations and experienced together are associated with an elevated rate of risk. Our findings suggest early cessation of smoking during pregnancy may be an effective strategy to reduce LMPT births.
Background: Although late and moderate prematurity (32-36 weeks´ gestation) represents 75% of pre... more Background: Although late and moderate prematurity (32-36 weeks´ gestation) represents 75% of preterm births, research in these infants is sparse. However, data from small or retrospective studies consistently suggest they are at greater risk of adverse outcomes than previously recognised. Aim: A prospective population-based study of outcomes of infants born at 32-36 weeks´ gestation.
American Journal of Obstetrics and Gynecology, Feb 1, 2018
BACKGROUND: Early-onset fetal growth restriction represents a particular dilemma in clinical mana... more BACKGROUND: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. OBJECTIVE: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. STUDY DESIGN: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. RESULTS: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/ 443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02e1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03e1.72) although birthweight and gestational age were more important determinants. CONCLUSION: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.
IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the ... more IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the esti...
Ultraschall in der Medizin - European Journal of Ultrasound, 2021
Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsat... more Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). Materials and Methods A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0–36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. Results 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2–4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight an...
ABSTRACTObjectivesTo explore the association between fetal umbilical and middle cerebral artery (... more ABSTRACTObjectivesTo explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction.MethodsThis was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20‐week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut‐off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored....
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 9, 2017
In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restrict... more In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. The primary outcome (two...
American journal of obstetrics and gynecology, Jan 10, 2017
Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal grow... more Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies. The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26(+0)-31(+6) weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use. This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26...
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 3, 2016
To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term feta... more To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term fetal heart rate (FHR) variation (STV) can be used for identifying imminent fetal distress and if abnormalities of FHR registration associate with two-year infant outcome. The original TRUFFLE study assessed if in early FGR the use of ductus venosus Doppler pulsatility index (DVPI), in combination with a safety-net of very low STV and / or recurrent decelerations, could improve two-year infant survival without neurological impairment in comparison to computerised cardiotocography (cCTG) with STV calculation only. For this secondary analysis we selected women, who delivered before 32 weeks, and who had consecutive STV data for more than 3 days before delivery, and known infant two-year outcome data. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values except the last one were calculated. Life table analysis and Cox...
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2014
ABSTRACT Infants born late/moderately preterm (LMPT; 32-36 weeks&amp;#39; gestation) have inc... more ABSTRACT Infants born late/moderately preterm (LMPT; 32-36 weeks&amp;#39; gestation) have increased risk of adverse outcomes compared with term-born infants. It is unclear whether differences relate to prematurity per se, or to problems occurring during pregnancy leading to medically indicated delivery.
Zeitschrift für Geburtshilfe und Neonatologie, 2015
Background Phase-rectified signal averaging, an innovative signal processing technique, can be us... more Background Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. Objective The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. Study Design Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European “TRUFFLE” trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. Results Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19–1.0]; delta short-term variation, 0.54 [confidence interval, 0.13–0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52–0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40–0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). Conclusion The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses
BackgroundOur aims were (1) to improve understanding of regional variation in early-life mortalit... more BackgroundOur aims were (1) to improve understanding of regional variation in early-life mortality rates and the UK’s poor performance in international comparisons; and (2) to identify the extent to which late and moderately preterm (LMPT) birth contributes to early childhood mortality and morbidity.ObjectiveTo undertake a programme of linked population-based research studies to work towards reducing variations in infant mortality and morbidity rates.DesignTwo interlinked streams: (1) a detailed analysis of national and regional data sets and (2) establishment of cohorts of LMPT babies and term-born control babies.SettingCohorts were drawn from the geographically defined areas of Leicestershire and Nottinghamshire, and analyses were carried out at the University of Leicester.Data sourcesFor stream 1, national data were obtained from four sources: the Office for National Statistics, NHS Numbers for Babies, Centre for Maternal and Child Enquiries and East Midlands and South Yorkshire ...
The American journal of clinical nutrition, Jan 30, 2015
Very preterm (<32 wk of gestation) infants are at increased risk of eating difficulties compar... more Very preterm (<32 wk of gestation) infants are at increased risk of eating difficulties compared with their term-born peers. Little is known about the impact of late and moderately preterm (LMPT; 32-36 wk of gestation) birth on eating difficulties in early childhood. The aims were to assess the prevalence of eating difficulties in infants born LMPT at 2 y corrected age and to explore the impact of neonatal and neurodevelopmental factors. A geographic population-based cohort of 1130 LMPT and 1255 term-born controls was recruited at birth. The parents of 651 (59%) LMPT and 771 (62%) term-born infants completed questionnaires at 2 y corrected age to assess neurodevelopmental outcomes. Parents also completed a validated questionnaire to assess eating behaviors in 4 domains: refusal/picky eating, oral motor problems, oral hypersensitivity, and eating behavior problems. Infants with scores >90th percentile were classified with eating difficulties in each domain. Neonatal data were c...
Journal of Developmental & Behavioral Pediatrics, 2015
Objective: To assess behavioral outcomes and social competence at 2 years of age in infants born ... more Objective: To assess behavioral outcomes and social competence at 2 years of age in infants born late and moderately preterm (LMPT; 32-36 wk gestation). Method: One thousand one hundred and thirty LMPT infants and 1255 term-born (‡37 wk) controls were recruited at birth to a prospective geographical population-based study. Parents completed the Brief Infant and Toddler Social Emotional Assessment (BITSEA) at 2 years corrected age to assess infants' behavior problems and social competence. Cognitive development was assessed using the Parent Report of Children's Abilities-Revised. Parent questionnaires at 2 years were completed for 638 (57%) LMPT and 765 (62%) term-born infants. Group differences in the prevalence of behavior problems and delayed social competence between LMPT infants and term-born controls were adjusted for age, sex, small-for-gestational-age, socioeconomic status and cognitive impairment. Results: Late and moderately preterm infants were at significantly increased risk of delayed social competence compared with term-born controls (26.4% vs 18.4%; adjusted-relative risk [RR] 1.28; 95% CI, 1.03-1.58), but there was no significant group difference in the prevalence of behavior problems (21.0% vs 17.6%; adjusted-RR 1.13, 0.89-1.42). Non-white ethnicity (RR 1.68, 1.26-2.24), medium (RR 1.60, 1.14-2.24) and high (RR 1.98, 1.41-2.75) socioeconomic risk and recreational drug use during pregnancy (RR 1.70, 1.03-2.82) were significant independent predictors of delayed social competence in LMPT infants. Conclusion: Birth at 32 to 36 weeks of gestation confers a specific risk for delayed social competence at 2 years of age. This may be indicative of an increased risk for psychiatric disorders later in childhood.
Objective: This study explores the associations between lifestyle factors and late and moderate p... more Objective: This study explores the associations between lifestyle factors and late and moderate preterm birth (LMPT: 32+0-36+6 weeks gestation), a relatively under-researched group. Study design: A population based case-cohort study was undertaken involving 922 LMPT and 965 term (37+ weeks gestation) singleton live and stillbirths born between 01/09/2009-31/12/2010 to women residing in Leicestershire and Nottinghamshire, UK. Poisson multivariable regression models were fitted to estimate relative risks (RR) of LMPT birth associated with maternal smoking, alcohol and recreational drug use, and diet. Results: Women who smoked during pregnancy were at 38% increased risk of LMPT birth compared to non-smokers (RR 1.38 95% CI (1.04 to 1.84)). Low consumption of fruit and vegetables was associated with a 31% increased risk compared to those who reported eating higher consumption levels (RR 1.31 (1.03 to 1.66)). Women who did not have any aspects of a Mediterranean diet were nearly twice as likely to deliver LMPT compared to those whose diet included more Mediterranean characteristics (RR 1.81 (1.04 to 3.14)). Women who smoked and consumed low levels of fruit and vegetables (5%) were at particularly high risk (RR=1.81 (1.29 to 2.55)). There was no significant effect of alcohol or recreational drug use on LMPT birth. Conclusions: Smoking and poor diet during pregnancy, factors that strongly impact on very preterm birth, are also important at later gestations and experienced together are associated with an elevated rate of risk. Our findings suggest early cessation of smoking during pregnancy may be an effective strategy to reduce LMPT births.
Background: Although late and moderate prematurity (32-36 weeks´ gestation) represents 75% of pre... more Background: Although late and moderate prematurity (32-36 weeks´ gestation) represents 75% of preterm births, research in these infants is sparse. However, data from small or retrospective studies consistently suggest they are at greater risk of adverse outcomes than previously recognised. Aim: A prospective population-based study of outcomes of infants born at 32-36 weeks´ gestation.
American Journal of Obstetrics and Gynecology, Feb 1, 2018
BACKGROUND: Early-onset fetal growth restriction represents a particular dilemma in clinical mana... more BACKGROUND: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. OBJECTIVE: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. STUDY DESIGN: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. RESULTS: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/ 443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02e1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03e1.72) although birthweight and gestational age were more important determinants. CONCLUSION: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension.
IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the ... more IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the esti...
Ultraschall in der Medizin - European Journal of Ultrasound, 2021
Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsat... more Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). Materials and Methods A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0–36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. Results 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2–4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight an...
ABSTRACTObjectivesTo explore the association between fetal umbilical and middle cerebral artery (... more ABSTRACTObjectivesTo explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction.MethodsThis was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20‐week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut‐off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored....
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 9, 2017
In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restrict... more In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. The primary outcome (two...
American journal of obstetrics and gynecology, Jan 10, 2017
Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal grow... more Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies. The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26(+0)-31(+6) weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use. This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26...
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 3, 2016
To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term feta... more To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term fetal heart rate (FHR) variation (STV) can be used for identifying imminent fetal distress and if abnormalities of FHR registration associate with two-year infant outcome. The original TRUFFLE study assessed if in early FGR the use of ductus venosus Doppler pulsatility index (DVPI), in combination with a safety-net of very low STV and / or recurrent decelerations, could improve two-year infant survival without neurological impairment in comparison to computerised cardiotocography (cCTG) with STV calculation only. For this secondary analysis we selected women, who delivered before 32 weeks, and who had consecutive STV data for more than 3 days before delivery, and known infant two-year outcome data. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values except the last one were calculated. Life table analysis and Cox...
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2014
ABSTRACT Infants born late/moderately preterm (LMPT; 32-36 weeks&amp;#39; gestation) have inc... more ABSTRACT Infants born late/moderately preterm (LMPT; 32-36 weeks&amp;#39; gestation) have increased risk of adverse outcomes compared with term-born infants. It is unclear whether differences relate to prematurity per se, or to problems occurring during pregnancy leading to medically indicated delivery.
Zeitschrift für Geburtshilfe und Neonatologie, 2015
Background Phase-rectified signal averaging, an innovative signal processing technique, can be us... more Background Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. Objective The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. Study Design Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European “TRUFFLE” trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. Results Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19–1.0]; delta short-term variation, 0.54 [confidence interval, 0.13–0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52–0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40–0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). Conclusion The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses
BackgroundOur aims were (1) to improve understanding of regional variation in early-life mortalit... more BackgroundOur aims were (1) to improve understanding of regional variation in early-life mortality rates and the UK’s poor performance in international comparisons; and (2) to identify the extent to which late and moderately preterm (LMPT) birth contributes to early childhood mortality and morbidity.ObjectiveTo undertake a programme of linked population-based research studies to work towards reducing variations in infant mortality and morbidity rates.DesignTwo interlinked streams: (1) a detailed analysis of national and regional data sets and (2) establishment of cohorts of LMPT babies and term-born control babies.SettingCohorts were drawn from the geographically defined areas of Leicestershire and Nottinghamshire, and analyses were carried out at the University of Leicester.Data sourcesFor stream 1, national data were obtained from four sources: the Office for National Statistics, NHS Numbers for Babies, Centre for Maternal and Child Enquiries and East Midlands and South Yorkshire ...
The American journal of clinical nutrition, Jan 30, 2015
Very preterm (<32 wk of gestation) infants are at increased risk of eating difficulties compar... more Very preterm (<32 wk of gestation) infants are at increased risk of eating difficulties compared with their term-born peers. Little is known about the impact of late and moderately preterm (LMPT; 32-36 wk of gestation) birth on eating difficulties in early childhood. The aims were to assess the prevalence of eating difficulties in infants born LMPT at 2 y corrected age and to explore the impact of neonatal and neurodevelopmental factors. A geographic population-based cohort of 1130 LMPT and 1255 term-born controls was recruited at birth. The parents of 651 (59%) LMPT and 771 (62%) term-born infants completed questionnaires at 2 y corrected age to assess neurodevelopmental outcomes. Parents also completed a validated questionnaire to assess eating behaviors in 4 domains: refusal/picky eating, oral motor problems, oral hypersensitivity, and eating behavior problems. Infants with scores >90th percentile were classified with eating difficulties in each domain. Neonatal data were c...
Journal of Developmental & Behavioral Pediatrics, 2015
Objective: To assess behavioral outcomes and social competence at 2 years of age in infants born ... more Objective: To assess behavioral outcomes and social competence at 2 years of age in infants born late and moderately preterm (LMPT; 32-36 wk gestation). Method: One thousand one hundred and thirty LMPT infants and 1255 term-born (‡37 wk) controls were recruited at birth to a prospective geographical population-based study. Parents completed the Brief Infant and Toddler Social Emotional Assessment (BITSEA) at 2 years corrected age to assess infants' behavior problems and social competence. Cognitive development was assessed using the Parent Report of Children's Abilities-Revised. Parent questionnaires at 2 years were completed for 638 (57%) LMPT and 765 (62%) term-born infants. Group differences in the prevalence of behavior problems and delayed social competence between LMPT infants and term-born controls were adjusted for age, sex, small-for-gestational-age, socioeconomic status and cognitive impairment. Results: Late and moderately preterm infants were at significantly increased risk of delayed social competence compared with term-born controls (26.4% vs 18.4%; adjusted-relative risk [RR] 1.28; 95% CI, 1.03-1.58), but there was no significant group difference in the prevalence of behavior problems (21.0% vs 17.6%; adjusted-RR 1.13, 0.89-1.42). Non-white ethnicity (RR 1.68, 1.26-2.24), medium (RR 1.60, 1.14-2.24) and high (RR 1.98, 1.41-2.75) socioeconomic risk and recreational drug use during pregnancy (RR 1.70, 1.03-2.82) were significant independent predictors of delayed social competence in LMPT infants. Conclusion: Birth at 32 to 36 weeks of gestation confers a specific risk for delayed social competence at 2 years of age. This may be indicative of an increased risk for psychiatric disorders later in childhood.
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