Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Foetal haemoglobin, blood transfusion, and retinopathy of prematurity in very preterm infants: a pilot prospective cohort study.

PurposeTo identify if there is an association between foetal haemoglobin (HbF) concentration and retinopathy of prematurity (ROP) in very preterm infants.Patients and methodsProspective cohort study. Infants born <32 weeks' gestational age or <1501 g in two tertiary neonatal units between January 2012 and May 2013 (n=42) were enrolled. HbF and adult haemoglobin (HbA) concentrations were measured using high-pressure liquid chromatography from blood samples sent as part of routine neonatal care once routinely requested laboratory tests had been performed. Clinical data were obtained from case notes. We calculated odds ratios (ORs) (95% confidence intervals (CIs)) to quantify the relationship between initial and mean %HbF with ROP severity (none, stages 1-3).ResultsA total of 42 infants were recruited: mean gestation 28.0 weeks (SD 1.91); mean birth weight 1042 g (SD 264). Six infants died before ROP screening; 14/36 developed ROP (39%); and 22/36 (61%) did not. Infants who developed ROP had similar initial %HbF (83.3 vs 92.3%, P=0.06), but significantly lower mean %HbF (61.75 vs 91.9%, P=0.0001) during their inpatient stay than those who did not develop ROP. In ordinal logistic regression models adjusted for birth weight, gestation and transfusion volume, mean post-natal %HbF was negatively associated with ROP severity: adjusted OR 0.94 (0.90-0.99), while initial %HbF at birth was not: adjusted OR 1.05 (0.97-1.16).ConclusionReplacing HbF by HbA during transfusion may promote ROP development by rapidly increasing oxygen availability to the retina. Conversely, maintaining a higher %HbF may be a protective factor against ROP.

Prevention of brachial plexus injury-12 years of shoulder dystocia training: an interrupted time-series study.

OBJECTIVE: To investigate management and outcomes of incidences of shoulder dystocia in the 12 years following the introduction of an obstetric emergencies training programme. DESIGN: Interrupted time-series study comparing management and neonatal outcome of births complicated by shoulder dystocia over three 4-year periods: (i) Pre-training (1996-99), (ii) Early training (2001-04), and (iii) Late training (2009-12). SETTING: Southmead Hospital, Bristol, UK, with approximately 6000 births per annum. POPULATION: Infants and their mothers who experienced shoulder dystocia. METHOD: A bi-monthly multi-professional 1-day intrapartum emergencies training course, that included a 30-minute practical session on shoulder dystocia management, commenced in 2000. MAIN OUTCOMES: Neonatal morbidity (brachial plexus injury, humeral fracture, clavicular fracture, 5-minute Apgar score <7) and documented management of shoulder dystocia (resolution manoeuvres performed, traction applied, head-to-body delivery interval). RESULTS: Compliance with national guidance improved with continued training. At least one recognised resolution manoeuvre was used in 99.8% (561/562) of cases of shoulder dystocia in the late training period, demonstrating a continued improvement from 46.3% (150/324, P < 0.001) pre-training, and 92% (241/262, P < 0.001) in the early training period. In parallel there was reduction in the brachial plexus injury at birth (24/324 [7.4%, P < 0.01], pre-training, 6/262 [2.3%] early training, and 7/562 [1.3%] late training. CONCLUSIONS: There are significant benefits to long-term, embedded training programmes with improvements in both management and outcomes. A decade after the introduction of training there were no cases of brachial plexus injury lasting over 12 months in 562 cases of shoulder dystocia.

Risk of low Apgar scores and socioeconomic status over a 30-year period.

OBJECTIVE: The aim of this study was to investigate the stability of associations between social factors, as assessed by maternal occupation and education, and poor birth condition (an Apgar score of below 7 at 1 and 5 minutes) over a 30-year period in Sweden. METHODS: The dataset was based on infants born in Sweden between 1973 and 2002. Poor birth condition was defined as an Apgar score below 7 at 1 and 5 minutes. Logistic regression was used to investigate the association of between socioeconomic status and poor birth condition. RESULTS: In the adjusted model, mothers in non-manual occupations (OR 0.91 (0.88, 0.95)) or with higher educational status (OR 0.88 (0.84, 0.93)) were less likely to have an infant born in poor condition than the reference group. Limiting the analysis to the last decade showed less evidence for an association (OR 0.94 (0.86, 1.02) and OR 0.94 (0.82, 1.09), respectively). CONCLUSIONS: While maternity, delivery and child healthcare are free of charge in Sweden, poor birth condition was more common among infants of mothers in manual occupations or low levels of education. However, this association appeared to attenuate over the calendar period studied.

Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort.

BACKGROUND: Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence. METHOD: A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy. RESULTS: The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11-1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14-10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97-2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12-1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia. CONCLUSIONS: Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course.

A cohort study of low Apgar scores and cognitive outcomes.

OBJECTIVE: To investigate the association of brief (0-5 minutes) and prolonged (>5 minutes) low Apgar scores (<7) in non-encephalopathic infants with educational achievement at age 15-16 and intelligence quotients (IQs) at age 18. DESIGN: Population-based record-linkage cohort study of 176 524 male infants born throughout Sweden between 1973 and 1976. PATIENTS AND METHODS: Data from the Medical Birth Register were linked to Population and Housing Censuses, conscription medical records (IQ), and school registers (summary school grade). Infants were classified according to the time for their Apgar score to reach 7 or above. Premature infants and those with encephalopathy were excluded. RESULTS: Infants with brief (OR = 1.14 (1.03-1.27)) or prolonged (OR = 1.35 (1.07-1.69)) low Apgar scores were more likely to have a low IQ score. There was an increased risk of a low IQ score (p = 0.003) the longer it took the infant to achieve a normal Apgar score. There was no association between brief (OR = 0.96 (0.87-1.06)) or prolonged (OR = 1.01 (0.81-1.26)) low Apgar scores and a low summary school grade at age 15-16, or evidence for a trend in the risk of a low school grade (p = 0.61). The estimated proportion with an IQ score below 81 due to transiently low Apgar scores was only 0.7%. CONCLUSIONS: Infants in poor condition at birth have increased risk of poor functioning in cognitive tests in later life. This supports the idea of a "continuum of reproductive casualty", although the small individual effect suggests that these mild degrees of fetal compromise are not of clinical importance.

Intraventricular streptokinase after intraventricular hemorrhage in newborn infants.

BACKGROUND: Hydrocephalus following intraventricular hemorrhage (IVH) is still one of the most serious complications of premature birth. Ventriculoperitoneal shunt surgery cannot be carried out early and permanent dependence on a shunt is associated with several serious complications. Streptokinase could be useful in the treatment of post-hemorrhagic hydrocephalus. This form of therapy is based on the hypothesis that multiple blood clots in the cerebrospinal fluid (CSF) are the initial cause of post-hemorrhagic ventricular dilatation and lysis of clots could reopen the pathways of circulation and re-absorption of CSF. OBJECTIVES: To determine the effect of intraventricular streptokinase after intraventricular hemorrhage on the risk of permanent shunt dependence, neurodevelopmental disability or death in neonates at risk for, or actually developing post-hemorrhagic hydrocephalus (PHH). SEARCH STRATEGY: Pediatric, Neurosurgical and General Medical Journals were handsearched from 1976 until October 2000, as well as the MEDLINE database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) up to April 2007. Personal contacts were used. SELECTION CRITERIA: Randomized controlled trials and quasi-randomized controlled trials evaluating the use of injection of streptokinase into the CSF in infants having or at risk for post-hemorrhagic hydrocephalus. DATA COLLECTION AND ANALYSIS: Details of patient selection, patient allocation and the interventions were extracted. The end-points examined were: ventriculoperitoneal shunt, death, meningitis, and secondary hemorrhage. MAIN RESULTS: Two randomized trials evaluated intraventricular streptokinase in infants developing post-hemorrhagic ventricular dilatation were identified When intraventricular streptokinase was compared with conservative management of post-hemorrhagic ventricular dilatation, the numbers of deaths and babies with shunt dependence were similar in both groups. No information on the effect of intraventricular streptokinase on disability is available. There is cause for concern about meningitis and secondary intraventricular hemorrhage, but numbers are insufficient to quantify the risks. AUTHORS' CONCLUSIONS: Intraventricular fibrinolytic therapy with streptokinase, given when post-hemorrhagic ventricular dilatation is established, cannot be recommended for neonates following IVH. A conservative approach with CSF drainage applied only to symptomatic raised intracranial pressure seems appropriate.

Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants.

BACKGROUND: Intraventricular hemorrhage (IVH) is a major complication of preterm birth. Large hemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals. OBJECTIVES: To determine the effect of postnatal administration of phenobarbital on the risk of intraventricular hemorrhage (IVH), neurodevelopmental impairment or death in preterm infants. SEARCH STRATEGY: See the Search Strategy of the Neonatal Collaborative Review Group. The reviewer has been a active trialist in this area and has personal contact with many groups in this field. Journals handsearched from 1976 (when cranial CT scanning started) to October 2000 include: Pediatrics, J Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European J of Pediatrics, Neuropediatrics, New England J of Medicine, Lancet and British Medical J. The National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) were searched through to April 2007 using the MeSH terms intraventricular hemorrhage, newborn infants, premature infant, intracranial hemorrhage, phenobarbitone, phenobarbital. The searches were not limited to the English language, as long as the article included an English abstract. Promising articles were read in the original language or translated. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g, or respiratory failure were included. Adequate determination of IVH by ultrasound or CT was also required. DATA COLLECTION AND ANALYSIS: In addition to details of patient selection and control of bias, the details of the administration of phenobarbital were extracted. The end-points searched for included: IVH ( with grading), posthemorrhagic ventricular dilatation or hydrocephalus, neurodevelopmental impairment and death. In addition, possible adverse effects of phenobarbitone such as hypotension, mechanical ventilation, pneumothorax, hypercapnia, and acidosis were searched for. MAIN RESULTS: Ten controlled trials were included with 740 infants recruited. There was heterogeneity between trials for the outcome IVH, with one trial finding a significant decrease in IVH and another trial finding an increase in IVH in the group receiving phenobarbital. Meta-analysis showed no difference between the phenobarbital treated group and the control group in either IVH (typical relative risk 1.04, 95% CI 0.87, 1.25), severe IVH (typical relative risk 0.91, 95% CI 0.66, 1.24), posthemorrhagic ventricular dilatation (typical relative risk 0.89, 95% CI 0.38, 2.08), severe neurodevelopmental impairment (typical relative risk 1.44, 95% CI 0.41, 5.04) or death before hospital discharge (typical relative risk 0.88, 95% CI 0.64, 1.21) There was a consistent trend in the trials towards increased use of mechanical ventilation in the phenobarbital treated group, which was supported by the meta-analysis (typical relative risk 1.18, 95% CI 1.06, 1.32; typical risk difference 0.129, 95% CI 0.045, 0.213), but there was no significant difference in pneumothorax, acidosis or hypercapnia. AUTHORS' CONCLUSIONS: Postnatal administration of phenobarbital cannot be recommended as prophylaxis to prevent IVH in preterm infants and is associated with an increased need for mechanical ventilation.

Variation in identifying neonatal percutaneous central venous line position.

OBJECTIVE: The study objective was to obtain data on interpretation, including intra and interobserver variation and action taken for a given line tip location, for a series of radiographs demonstrating neonatal long lines. METHODS: Nineteen radiographs taken to identify line tip position were digitized and published on an internet site. One film was included twice in order to assess intraobserver variation giving a total of 20 images. Fourteen used radio-opaque contrast and five no contrast. Australian and New Zealand Neonatal Network members and National Women's Hospital NICU staff were invited to participate in the study. For each radiograph, participants were asked to identify if long line tip could be identified, the likely anatomical position and desired action. Interobserver agreement was assessed by the maximum proportion of agreement per radiograph and by the number of different options selected. Intraobserver agreement was assessed by comparing the two reports from the duplicate radiograph. RESULTS: Twenty-seven responses were received. Overall, 50% of the reports stated that the long line tips could be identified. The most commonly reported position was in the right atrium (31%) and most commonly reported action was to pull the line back (53%). The median agreement of whether the line was seen was 68%, agreement on position 62% and agreement on action 86%. On analysis of intraobserver variability, from the identical radiographs, 27% of respondents differed on whether the line tip could be visualized. CONCLUSION: Interobserver and intraobserver reliability was poor when using radiographs to assess long line tips. The major determinant of line repositioning was the perceived location.

A randomized trial of two dexamethasone regimens to reduce side-effects in infants treated for chronic lung disease of prematurity.

OBJECTIVE: Dexamethasone has been widely used to reduce the incidence of chronic lung disease in preterm infants. However side-effects are common, and the ideal dose of dexamethasone has not been identified. We aimed to determine whether an individualized course of dexamethasone given to preterm babies at risk of chronic lung disease reduced the total dose of dexamethasone administered and reduced side-effects compared with a standard 42-day course. METHODS: Thirty-three infants in a regional neonatal unit with a birthweight of < or =1250 g who required mechanical ventilation at 7 days of age were randomly assigned to a 42-day course of dexamethasone or an individualized course tailored to their respiratory status. The primary outcome was linear growth at 36 weeks corrected gestational age. RESULTS: Infants in the individualized course received a 40% lower total dose of dexamethasone. However, there was no difference between the two groups in linear growth or in the incidence of any other side-effects of treatment. There was also no difference in respiratory status or neurodevelopmental outcome. CONCLUSION: The individualized course of dexamethasone used in this study reduced the total dose of dexamethasone administered but did not significantly reduce side-effects of treatment or alter outcome in infants at risk of chronic lung disease.

Does radio-opaque contrast improve radiographic localisation of percutaneous central venous lines?

BACKGROUND: Percutaneous central venous lines (long lines) are commonly used in neonatal practice. The position of these lines is important, because incorrect placement may be associated with complications. AIMS: To determine whether the addition of radio-opaque contrast material improves the localisation of long line tips over plain radiography. METHODS: Radiographs taken to identify long line position were identified in two periods; 106 radiographs without contrast taken between October 1999 and August 2000, and 96 radiographs with contrast between September 2001 and July 2002. Two observers independently reviewed each radiograph to identify the position of the line tip. The formal radiology report was recorded as a third observer. RESULTS: The use of contrast increased the proportion of radiographs in which all observers reported they could see the long line tip (53 (55%) v 41 (39%)). It also increased the proportion where they agreed on anatomical position (57 (59%) v 39 (37%)) and there was a higher kappa coefficient for agreement (0.56 v 0.33). CONCLUSIONS: The use of contrast while taking radiographs for the localisation of long line position improves the likelihood that an observer can see a long line tip and reduces inter-observer variability. Even using contrast, precise localisation of a long line tip can be difficult.

Primary pulmonary hypoplasia: a case report and review of the literature.

A case of primary pulmonary hypoplasia in a term female neonate presenting with severe respiratory distress at birth is reported. Respiratory failure persisted and she died at 12 days of age. Primary pulmonary hypoplasia is a rare condition not associated with other maternal or fetal disorders.