Women's experiences of participating in a randomised trial comparing alternative policies for timing of cord clamping at very preterm birth: a questionnaire study

BACKGROUND: The Cord Pilot Trial compared two alternative policies for cord-clamping at very preterm birth at eight UK tertiary maternity units: clamping after at least 2 min and immediate neonatal care with cord intact, or clamping within 20 s and neonatal care after clamping. This paper reports views and experiences of the women who participated in the trial (261 randomised), based on data from two self-completed questionnaires. METHODS: Women were given or posted the first questionnaire between 4 and 8 weeks after birth, and posted a second similar questionnaire at 1 year. Both questionnaires included three questions about experiences of participating in the trial: (1) If time suddenly went backwards and you had to do it all over again, would you agree to participate in the Cord Pilot Trial?; (2) Please tell us if there was anything about the Cord Pilot Trial that you think could have been done better; and (3) Please tell us if there was anything about the Cord Pilot Trial, or your experiences of joining the trial, that you think were particularly good. RESULTS: One hundred and eighty-six women completed the first questionnaire and 133 completed the second. At both time points, 90% responded 'probably' or 'definitely' to participating in the trial again. More women randomised to deferred clamping responded 'definitely yes' than those allocated immediate clamping (78% versus 67% first questionnaire). Women were positive about the level of information and explanations, the friendly and caring staff, and the benefits for their baby and others as a result of participating in the trial. Suggestions for how the trial could be done better included being approached earlier, better staff communication about the trial, more information overall, and better timing of follow-up. CONCLUSIONS: Women were largely positive about participating in the trial. Nevertheless, they had suggestions for how the study could have been improved. These suggestions have implications for the design of future trials. TRIAL REGISTRATION: ISRCTN21456601 . Registered on 28 February 2013

Cord pilot trial, comparing alternative policies for timing of cord clamping before 32 weeks gestation: follow-up for women up to one year.

BACKGROUND: The Cord Pilot Trial compared two alternative policies for cord clamping at very preterm birth at eight UK maternity units: clamping after at least 2 min and immediate neonatal care (if needed) with cord intact, or clamping within 20 s and neonatal care after clamping. This paper reports follow-up of the women by two self-completed questionnaires up to one year after the birth. METHODS: Women were given or posted the first questionnaire between four and eight weeks after birth, usually before their baby was discharged, and were posted a second similar questionnaire at one year. The questionnaire included the Hospital Anxiety and Depression Scale; the Preterm Birth Experience and Satisfaction Scale (P-BESS) and questions about their baby's feeding. RESULTS: Of 261 women randomised (132 clamping ≥2 min, 129 clamping ≤20 s), six were excluded as birth was after 35+ 6 weeks (2, 4 in each group respectively). Six were not sent either questionnaire. The first questionnaire was given/sent to 244 and returned by 186 (76%) (79, 74%). The second, at one year, was sent to 242 and returned by 133 (55%) (66, 43%). On the first questionnaire, 89 (49%) had a score suggestive of an anxiety disorder, and 55 (30%) had a score suggestive of depression. Satisfaction with care at birth was high: median total P-BESS score 77 [interquartile range 68 to 84] (scale 17 to 85). There was no clear difference in anxiety, depression, or satisfaction with care between the two allocated groups. The median number of weeks after birth women breastfed/expressed was 16 (95% confidence interval (CI) 13 to 20, n = 119) for those allocated clamping ≥2 min and 12 (95% CI 11 to 16, n = 103) for those allocated clamping ≤20 s. CONCLUSIONS: The response rate was higher for the earlier questionnaire than at one year. A high proportion of women reported symptoms of anxiety or depression, however there were no clear differences between the allocated groups. Most women reported that they had breastfed or expressed milk and those allocated deferred cord clamping reported continuing this for slightly longer. TRIAL REGISTRATION: ISRCTN 21456601, registered 28th February 2013, http://www.isrctn.com/ISRCTN21456601

Cerebellar Zones: A Personal History

Cerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because three groups, in Leiden, Lund, and Bristol, using different approaches, stumbled on the same zonal pattern in the cerebellum of the cat. In Leiden, the Häggqvist myelin stain divulged the compartments in the cerebellar white matter that channel the afferent and efferent connections of the zones. In Lund, the spino-olivocerebellar pathways activated from individual spinal funiculi revealed the zonal pattern. In Bristol, charting the axon reflex of olivocerebellar climbing fibers on the surface of the cerebellum resulted in a very similar zonal map. The history of the zones is one of accidents and purposeful pursuit. The technicians, librarians, animal caretakers, students, secretaries, and medical illustrators who made it possible remain unnamed, but their contributions certainly should be acknowledged

The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0 weeks' gestation.

BackgroundStillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth.MethodsPLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman's pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians.DiscussionOur aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus.Trial registrationISRCTN58254381 . Registered on 4 July 2019

Randomised trial of cord clamping at very preterm birth: outcomes at 2 years

Objective: To report outcomes at 2 years corrected age for children of women recruited to a trial comparing alternative policies for timing of cord clamping and immediate neonatal care at very preterm birth. Design: Parallel group randomised (1:1) trial. Setting: Eight UK tertiary maternity units. Participants: Two hundred and seventy six babies born to 261 women expected to have a livebirth before 32+0 weeks gestation. Interventions: Deferred cord clamping (≥2 minutes) and immediate neonatal care with cord intact, or immediate (≤20 seconds) clamping and immediate neonatal care after clamping. Main outcome measure: Composite of death or adverse neurodevelopmental outcome at 2 years corrected age. Results: Six babies born after 35+6 weeks were excluded. At 2 years corrected age, outcome data were not available for a further 52 children, leaving 218 for analysis (115 deferred clamping, 103 immediate clamping). Overall, 24/115 (21%) children allocated deferred clamping died or had an adverse neurodevelopmental outcome compared with 35/103 (34%) allocated immediate clamping; relative risk (RR) 0.61 (95% confidence interval [CI] 0.39 to 0.96); risk difference (RD) -13% (95% CI -25% to -1%). Multiple imputation for missing data gave a RR 0.69 (95% CI 0.44 to 1.09) and RD -9% (95% CI -21% to 2%). Conclusions: Deferred clamping and immediate neonatal care with cord intact may reduce the risk of death or adverse neurodevelopmental outcome at 2 years of age for children born very premature. Confirmation in larger studies is needed to determine the real benefits and harms

PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus

The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage