Sandra Calvert

Neonatal and infant outcome in boys and girls born very prematurely

Introduction: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.Results: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.Discussion: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.Methods: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.

Risk factors for respiratory morbidity in infancy after very premature birth

Objectives: To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors. Design: Prospective follow up study. Setting: The United Kingdom oscillation study. Patients: 492 infants, all born before 29 weeks gestation. Interventions: Structured questionnaires were completed by local paediatricians when the infants were seen in outpatients at 6 and 12 months of age corrected for prematurity. Main outcome measures: Cough, wheeze, and treatment requirements and the composite measure of respiratory morbidity (cough, frequent cough, cough without infection, wheeze, frequent wheeze, wheeze without infection, and use of chest medicine) and their relation to 13 possible explanatory variables. Results: At 6 and 12 months of corrected age, 27% of the infants coughed and 6% had frequent (more than once a week) cough, and 20% and 3% respectively had wheeze or frequent wheeze. At 6 and 12 months, 14% of infants had taken bronchodilators and 8% inhaled steroids. After adjustment for multiple outcome testing, four factors were associated with increased respiratory morbidity: male sex, oxygen dependency at 36 weeks postmenstrual age, having older siblings aged less than 5 years, and living in rented accommodation. Conclusions: Male infants are particularly vulnerable to respiratory morbidity in infancy after very premature birth. It is important to identify a safe and effective strategy to prevent chronic oxygen dependency.

Prenatal diagnosis of non‐immune hydrops fetalis: what do we tell the parents?

The aim of this study is to outline the aetiology and outcome of a series of fetuses with non‐immune hydrops (NIH), detected prenatally. The findings are compared with a comprehensive review of recent reports.

Very prematurely born infants wheezing at follow-up: lung function and risk factors

Objectives: 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. Design: 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. Setting: Infant pulmonary function laboratory. Patients: 111 infants (mean gestational age 26.3 (SD 1.6) weeks). Interventions: Lung function measurements at 1 year of age corrected for gestational age at birth. Diary cards and respiratory questionnaires were completed to document wheeze. Main outcome measures: Functional residual capacity (FRCpleth and FRCHe), airways resistance (Raw), FRCHe:FRCpleth and tidal breathing parameters (TPTEF:TE). Results: The 60 infants who wheezed at follow-up had significantly lower mean FRCHe, FRCHe:FRCpleth and TPTEF:TE, but higher mean Raw than the 51 without wheeze. Regression analysis demonstrated that gestational age, length at assessment, family history of atopy and a low FRCHe:FRCpleth were significantly associated with wheeze. Conclusions: Wheeze at follow-up in very prematurely born infants is associated with gas trapping, suggesting abnormalities of the small airways.

Reduction in ventilator-induced lung injury improves outcome in congenital diaphragmatic hernia?

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.

Respiratory function of very prematurely born infants at follow up: influence of sex

Objective: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. Design: Prospective follow up study. Setting: Tertiary neonatal intensive care units Patients: Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study. Interventions: Lung function measurements at a corrected age of 1 year. Main outcome measures: Airways resistance (Raw) and functional residual capacity (FRCpleth) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRCpleth, and FRC measured by a helium gas dilution technique (FRCHe). Results: The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRCpleth were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRCpleth and sGaw were 15% and 26% respectively and remained significant. Conclusion: Lung function at follow up of prematurely born infants is influenced by sex.

Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study

BackgroundBronchopulmonary 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.MethodsWe 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.ResultsWe 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.ConclusionsExternal 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.

Respiratory morbidity at follow-up of small-for-gestational-age infants born very prematurely.

Background:The aim of this study was 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 recruited into the United Kingdom Oscillation Study (UKOS). Of the 797 infants who were born at <29 wk of gestational age, 174 infants were SGA. Overall, 92% were exposed to antenatal corticosteroids and 97% received surfactant; follow-up data at 22–28 mo were available for 367 infants.Results:After adjustment for gestational age and sex, SGA infants had higher rates of supplementary oxygen dependency at 36 wk postmenstrual age (odds ratio (OR): 3.23; 95% confidence interval: 2.03, 5.13), pulmonary hemorrhage (OR: 3.07; 95% CI: 1.82, 5.18), death (OR: 3.32; 95% CI: 2.13, 5.17), and postnatal corticosteroid requirement (OR: 2.09; 95% CI: 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; 95% CI: 1.03, 1.88 for 1 SD change in z-score), cough (OR: 1.28; 95% CI: 1.00, 1.65), and use of chest medicines (OR: 1.32; 95% CI: 1.01, 1.73).Conclusion:SGA infants who were born very prematurely, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity at follow-up, which was not due to poor neonatal outcome.

The Effects of Acute Uterine Ischemia on Fetal Circulation1

ABSTRACT: The effects of acute maternal hemorrhage on uterine blood flow and fetal circulation were investigated in pregnant sheep. Nine chronically instrumented pregnant sheep (114–128 d gestation), phlebotomized from the iliac artery at the point of origin of the uterine artery, were studied at baseline, after acute hemorrhage, and immediately and two h after replacement of the blood. Maternal hemorrhage caused a reduction in uterine blood flow as well as both fetal hypoxemia and acidemia. Changes in fetal organ blood flow measured by radionuclide-labeled microspheres showed that blood flow to the brain, heart, and adrenal glands increased (p<0.05), whereas blood flow to the other major organs did not change significantly. Rapid replacement of blood restored all parameters to baseline values. We conclude that acute maternal hemorrhage causes a reduction in uterine blood flow, fetal hypoxemia, and acidemia with a secondary increase in blood flow to the high priority organs. Rapid replacement of blood reverses these effects.

The Role of High Frequency Oscillatory Ventilation in Very Preterm Infants

The role of high frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Animal work demonstrates reduced lung injury with HFOV compared to conventional ventilation (CV), and previous human trials suggest that in preterm infants HFOV reduces the incidence of chronic lung disease (CLD). However, the trials themselves have several limitations. In an attempt to conclusively establish the role of HFOV for the prevention of CLD in very preterm infants we conducted a large, UK based, multicentre trial. Preliminary results of this study suggest there are no significant differences between the two modes of ventilation regarding mortality and incidence of CLD.