Sandra A Calvert

King's College London, London, ENG, United Kingdom

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Publications (15)227.55 Total impact

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    ABSTRACT: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 26·1-40·6) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 144, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 03/2015; DOI:10.1016/S0140-6736(14)62049-3 · 45.22 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.
    BMC Pediatrics 12/2013; 13(1):207. DOI:10.1186/1471-2431-13-207 · 1.92 Impact Factor
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    ABSTRACT: Background:To determine whether small for gestational age (SGA) infants, born very prematurely had increased respiratory morbidity in the neonatal period and at follow up.Methods:Data were examined from infants entered into the United Kingdom Oscillation Study (UKOS). 174 of 797 infants who were born at less than 29 weeks of gestational age, were SGA. Overall, 92% were exposed to antenatal corticosteroids and 97% received surfactant and follow up data at 22-28 months were available for 367 infants.Results:After adjustment for gestational age and sex, SGA infants had higher rates of supplementary oxygen dependency at 36 weeks postmenstrual age (OR: 3.23; 95% CI 2.03, 5.13), pulmonary haemorrhage (3.07; 1.82, 5.18), death (3.32; 2.13, 5.17) and postnatal corticosteroid requirement (2.09;1.35,3.23). After adjustment for infant and respiratory morbidity risk factors, a lower mean birth weight z- score was associated with a higher prevalence of respiratory admissions (OR 1.40; 1.03, 1.88 for one standard deviation change in z score), cough (1.28; 1.00, 1.65) and use of chest medicines (1.32; 1.01, 1.73).Conclusion:Small for gestational age, very prematurely born infants, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity at follow up, which was not due to poor neonatal outcome.Pediatric Research (2012); doi:10.1038/pr.2012.201.
    Pediatric Research 12/2012; DOI:10.1038/pr.2012.201 · 2.84 Impact Factor
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    ABSTRACT: Although important new strategies have improved outcomes for very preterm infants, males have greater mortality/morbidity than females. We investigated whether the excess of adverse later effects in males operated through poorer neonatal profile or if there was an intrinsic male effect. Male sex was significantly associated with higher birth weight, death or oxygen dependency (72% vs. 61%, boys vs. girls), hospital stay (97 vs. 86 days), pulmonary hemorrhage (15% vs. 10%), postnatal steroids (37% vs. 21%), and major cranial ultrasound abnormality (20% vs. 12%). Differences remained significant after adjusting for birth weight and gestation. At follow-up, disability, cognitive delay, and use of inhalers remained significant after further adjustment. We conclude that in very preterm infants, male sex is an important risk factor for poor neonatal outcome and poor neurological and respiratory outcome at follow-up. The increased risks at follow-up are not explained by neonatal factors and lend support to the concept of male vulnerability following preterm birth. Data came from the United Kingdom Oscillation Study, with 797 infants (428 boys) born at 23-28 wk gestational age. Thirteen maternal factors, 8 infant factors, 11 acute outcomes, and neurological and respiratory outcomes at follow-up were analyzed. Follow-up outcomes were adjusted for birth and neonatal factors sequentially to explore mechanisms for differences by sex.
    Pediatric Research 03/2012; 71(3):305-10. DOI:10.1038/pr.2011.50 · 2.84 Impact Factor
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    The Lancet 05/2011; 12(375):2082-91. · 45.22 Impact Factor
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    ABSTRACT: BACKGROUND: Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. METHODS: We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. FINDINGS: For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. INTERPRETATION: HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. FUNDING: Nestlé Belgium, Belgian Red Cross, and Dräger International.
    The Lancet 05/2010; DOI:10.1016/S0140-6736(10)60278-4 · 45.22 Impact Factor
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    ABSTRACT: Studies of prematurely born infants contain a relatively large percentage of multiple births, so the resulting data have a hierarchical structure with small clusters of size 1, 2 or 3. Ignoring the clustering may lead to incorrect inferences. The aim of this study was to compare statistical methods which can be used to analyse such data: generalised estimating equations, multilevel models, multiple linear regression and logistic regression. Four datasets which differed in total size and in percentage of multiple births (n = 254, multiple 18%; n = 176, multiple 9%; n = 10 098, multiple 3%; n = 1585, multiple 8%) were analysed. With the continuous outcome, two-level models produced similar results in the larger dataset, while generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) produced divergent estimates using the smaller dataset. For the dichotomous outcome, most methods, except generalised least squares multilevel modelling (ML GH 'xtlogit' in Stata) gave similar odds ratios and 95% confidence intervals within datasets. For the continuous outcome, our results suggest using multilevel modelling. We conclude that generalised least squares multilevel modelling (ML GLS 'xtreg' in Stata) and maximum likelihood multilevel modelling (ML MLE 'xtmixed' in Stata) should be used with caution when the dataset is small. Where the outcome is dichotomous and there is a relatively large percentage of non-independent data, it is recommended that these are accounted for in analyses using logistic regression with adjusted standard errors or multilevel modelling. If, however, the dataset has a small percentage of clusters greater than size 1 (e.g. a population dataset of children where there are few multiples) there appears to be less need to adjust for clustering.
    Paediatric and Perinatal Epidemiology 08/2009; 23(4):380-92. DOI:10.1111/j.1365-3016.2009.01046.x · 2.81 Impact Factor
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    ABSTRACT: The purpose of this historical study was to compare the outcome for two treatment strategies, for neonates with congenital diaphragmatic hernia (CDH). The records of 65 infants born between 1991 and 2005 with CDH from a single tertiary care perinatal centre in the United Kingdom were retrospectively reviewed. Conventional mechanical ventilation (CMV) and systemic vasodilators were used from 1991 to 1995 (era 1). High frequency oscillatory ventilation (HFOV) and nitric oxide (NO) were used between 1996 and 2005 (era 2). Main outcome measures were survival and incidence of chronic lung disease. The results showed that the survival rate was 38% (8/21) in era 1 and 73% (32/44) in era 2, 95% CI for difference -59 to -10%. The incidence of chronic lung disease in survivors was 45% (5/11) in era 1 and 30% (9/30) in era 2, 95% CI for difference -18 to 49%. These data show significantly improved survival with elective use of HFOV and NO compared to CMV and systemic vasodilators. The survival results for CDH at St George's Hospital are comparable to those published from other institutions. The results may reflect a reduction in ventilator-induced lung injury with HFOV compared to CMV.
    Pediatric Surgery International 03/2008; 24(2):145-50. DOI:10.1007/s00383-007-2051-2 · 1.06 Impact Factor
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    ABSTRACT: To determine whether abnormalities of lung volume and/or airway function were associated with wheeze at follow-up in infants born very prematurely and to identify risk factors for wheeze. Lung function data obtained at 1 year of age were collated from two cohorts of infants recruited into the UKOS and an RSV study, respectively. Infant pulmonary function laboratory. 111 infants (mean gestational age 26.3 (SD 1.6) weeks). Lung function measurements at 1 year of age corrected for gestational age at birth. Diary cards and respiratory questionnaires were completed to document wheeze. Functional residual capacity (FRC(pleth) and FRC(He)), airways resistance (R(aw)), FRC(He):FRC(pleth) and tidal breathing parameters (T(PTEF):T(E)). The 60 infants who wheezed at follow-up had significantly lower mean FRC(He), FRC(He):FRC(pleth) and T(PTEF):T(E), but higher mean R(aw) than the 51 without wheeze. Regression analysis demonstrated that gestational age, length at assessment, family history of atopy and a low FRC(He):FRC(pleth) were significantly associated with wheeze. Wheeze at follow-up in very prematurely born infants is associated with gas trapping, suggesting abnormalities of the small airways.
    Archives of Disease in Childhood 10/2007; 92(9):776-80. DOI:10.1136/adc.2006.112623 · 2.91 Impact Factor
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    ABSTRACT: Language development is often slower in preterm children compared with their term peers. We investigated factors associated with vocabulary acquisition at 2 years in a cohort of children born at 28 weeks' gestation or less. For children entered into the United Kingdom Oscillation Study, language development was evaluated by using the MacArthur-Bates Communicative Development Inventories score, completed by parents as part of a developmental questionnaire. The effect of demographic, neonatal, socioeconomic factors, growth, and disability were investigated using multifactorial random effects modelling. Questionnaires were returned by 288 participants (148 males, 140 females). The mean number of words vocalized was 42 (SD 29). Multifactorial analysis showed only four factors were significantly associated with vocabulary acquisition. These were: (1) level of disability (mean words: no disability, 45; other disability, 38; severe disability, 30 [severe disability is defined as at least one extreme response in one of the following clinical domains: neuromotor, vision, hearing, communication, or other physical disabilities]; 95% confidence interval [CI] for the difference between no and severe disability 7- 23); (2) sex (39 males, 44 females; 95% CI 0.4-11); (3) length of hospital stay (lower quartile, 47; upper quartile, 38; 95% CI -12 to -4); and (4) weight SD score at 12 months (lower quartile, 39; upper quartile, 44; 95% CI 1-9). There was no significant association between gestational age and vocabulary after multifactorial analysis. There was no significant effect of any socioeconomic factor on vocabulary acquisition. We conclude that clinical factors, particularly indicators of severe morbidity, dominate the correlates of vocabulary acquisition at age 2 in children born very preterm.
    Developmental Medicine & Child Neurology 09/2007; 49(8):591-6. DOI:10.1111/j.1469-8749.2007.00591.x · 3.29 Impact Factor
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    ABSTRACT: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26-28 weeks. Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 10/2006; 91(5):F320-6. DOI:10.1136/adc.2005.079632 · 3.86 Impact Factor
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    ABSTRACT: The appearance of the chest radiograph (CXR) at 28 days after birth or 36 weeks post-menstrual age (PMA) has been shown to be predictive of respiratory symptoms at follow-up. The aim of this study was to determine whether the CXR appearance at 28 days or 36 weeks PMA differed according to the ventilatory mode used in the perinatal period. CXRs were routinely obtained at 28 days and 36 weeks PMA from infants entered into a multicentre randomised trial (UKOS) comparing high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV); the ventilation allocation mode had been instituted within 60 min of birth. The CXRs were assessed using a scoring system (maximum score 8) for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. A total of 487 infants, median gestational age 26+5 weeks (range 23-28+6 weeks) and birth weight 865 g (range 428-1459 g) who had had a CXR taken at 28 days and/or 36 weeks PMA. No significant differences were found between the total CXR scores of the two groups either at 28 days or 36 weeks PMA (mean scores 3.2 HFOV versus 3.5 CMV, 95%CI for difference -0.66 to 0.06, P=0.11 at 28 days and mean scores 3.5 HFOV versus 3.6 CMV, 95% for difference -0.49 to 0.29, P=0.61 at 36 weeks PMA). CONCLUSION: These results are consistent with high frequency oscillatory ventilation and conventional mechanical ventilation having similar effects on pulmonary function in very prematurely born infants.
    European Journal of Pediatrics 12/2004; 163(11):671-4. DOI:10.1007/s00431-004-1526-6 · 1.98 Impact Factor
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    ABSTRACT: Prematurely born infants supported by conventional ventilation (CV) frequently have abnormal pulmonary function when assessed in childhood. The aim of this study was to test the hypothesis that infants who were randomly assigned to high-frequency oscillatory ventilation would have superior pulmonary function at follow-up compared with those who received CV (UK Oscillation Study). Infants from 12 trial centers were recruited for pulmonary function testing at a single center. Seventy-six infants, of a mean gestational age 26.4 weeks, were studied after sedation with chloral hydrate at between 11 and 14 months of age, corrected for prematurity. Infants assigned to CV had similar pulmonary function compared with those assigned to high-frequency oscillatory ventilation, with mean (SD) results as follows: functional residual capacity measured by whole-body plethysmography, 26.9 (6.3) versus 26.5 (6.4) ml/kg; functional residual capacity measured by helium dilution, 24.1 (5.4) versus 23.5 (5.7) ml/kg; inspiratory airway resistance, 3.3 (1.3) versus 3.4 (1.6) kPa. second. L; expiratory airway resistance, 4.4 (2.8) versus 4.1 (2.5) kPa. second. L; respiratory rate, 31.2 (6.0) versus 33.9 (8.0) breaths/minute. We conclude that early use of high-frequency oscillatory ventilation in very preterm infants appears to offer no advantage over CV in terms of pulmonary function at follow-up.
    American Journal of Respiratory and Critical Care Medicine 05/2004; 169(7):868-72. DOI:10.1164/rccm.200310-1425OC · 11.99 Impact Factor
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    ABSTRACT: Our aim was to determine whether the chest radiograph appearance at 7 days predicted chronic lung disease development (oxygen dependency at 36 weeks post-menstrual age) or death before discharge and if it was a better predictor than readily available clinical data. Two consecutive studies were performed. In both, chest radiographs taken at 7 days for clinical purposes were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation and data were collected regarding gestational age, birth weight, use of antenatal steroids and post-natal surfactant and requirement for ventilation at 7 days. Oxygenation indices were calculated in the first study (study A) at 120 h and in the second (study B) at 168 h. In study A, there were 59 infants with a median gestational age of 26 weeks (range 24 to 28 weeks) and in study B, 40 infants with a median gestational age of 27 weeks (range 25-31 weeks). In both studies, infants who developed chronic lung disease had a significantly higher total chest radiograph score, with a higher score for fibrosis/interstitial shadowing than the rest of the cohort. Infants who died before discharge differed significantly from the rest with regard to significantly higher scores for cysts. In both studies, the areas under the receiver operator characteristic curves with regard to prediction of chronic lung disease were higher for the total chest radiograph score compared to those for readily available clinical data. CONCLUSION: In infants who require a chest radiograph for clinical purposes at 7 days, the chest radiograph appearance can facilitate prediction of outcome of infants born very prematurely.
    European Journal of Pediatrics 02/2004; 163(1):14-8. DOI:10.1007/s00431-003-1332-6 · 1.98 Impact Factor
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    ABSTRACT: There remains uncertainty concerning the safety and efficacy of high-frequency oscillatory ventilation as compared with those of conventional ventilation for the respiratory support of very preterm infants. We conducted a multicenter trial to determine whether early intervention with high-frequency oscillatory ventilation reduced mortality and the incidence of chronic lung disease among newborns with a gestational age of 28 weeks or less. We randomly assigned preterm infants with a gestational age of 23 to 28 weeks to either conventional ventilation or high-frequency oscillatory ventilation within one hour after birth. Randomization was stratified according to center and gestational age (23 to 25 weeks or 26 to 28 weeks). A total of 400 infants were assigned to high-frequency oscillatory ventilation, and 397 were assigned to conventional ventilation. The composite primary outcome (death or chronic lung disease, diagnosed at 36 weeks of postmenstrual age) occurred in 66 percent of the infants assigned to receive high-frequency oscillatory ventilation and 68 percent of those in the conventional-ventilation group (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.98; 95 percent confidence interval, 0.89 to 1.08). Similar proportions of infants died or had chronic lung disease in each gestational-age group. In both treatment groups treatment failure occurred in 10 percent of infants (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.99; 95 percent confidence interval, 0.66 to 1.50). There were no significant differences between the groups in a range of other secondary outcome measures, including serious brain injury and air leak. The results obtained with high-frequency oscillatory ventilation and conventional ventilation do not differ significantly in the early treatment of respiratory disease in very preterm infants. Assessment of long-term effects will require additional follow-up.
    New England Journal of Medicine 09/2002; 347(9):633-42. DOI:10.1056/NEJMoa020432 · 54.42 Impact Factor

Publication Stats

422 Citations
227.55 Total Impact Points


  • 2012
    • King's College London
      • Division of Health and Social Care Research
      London, ENG, United Kingdom
  • 2009
    • St. George's University
      Mississippi, United States
  • 2007
    • University of London
      Londinium, England, United Kingdom
  • 2006–2007
    • Brunel University London
      • School of Health Sciences and Social Care
      अक्सब्रिज, England, United Kingdom