Study participants
Eligibility
Our original plan was for recruitment to take place over a 1-year period between September 2009 and August 2010. All mothers who were resident in a geographically defined area of Leicestershire and
Nottinghamshire and delivered babies at 32+0–36+6weeks’gestation were eligible to participate in the
study with their babies. There were no exclusion criteria. We also identified a group of babies born at term
(≥37 weeks’gestation) during the same time period and geographical region that would be recruited as
a control group.
However, towards the end of the proposed 12-month recruitment period it became apparent that the target sample size of 800 singleton births in each group was unlikely to be met. An extension of the recruitment period was agreed with the ethics committee and recruitment continued until 31 December 2010.
Participating centres
We used a population-based design for the study to allow evaluation of the risks and outcomes within a regional population. The geographical area covered by the study comprised rural and urban populations, as well as a diverse range of ethnicities and a wide socioeconomic spectrum. This avoided the bias
introduced in hospital-based studies, which often leads to recruitment of a study population with artificially elevated risk compared with the population as a whole. Within the chosen geographical area around Leicester and Nottingham, there were four hospitals and one community birth centre that provided maternity services to the population. Two hospitals in Nottingham provided all levels of neonatal care,
from intensive care to low-dependency or‘special’care, with a total of approximately 10,000 deliveries
annually. In Leicester, where there are also approximately 10,000 deliveries in total each year, one hospital provided both neonatal intensive and low-dependency care while the other provided low-dependency care only. In each of the two cities a single team of consultant neonatologists working across the two hospital sites provided medical management of neonatal care. Therefore, although infants were cared for in four separate geographical locations, for the purposes of delivery of neonatal care, these could be regarded as two neonatal centres. Both centres were regional referral units for women with complicated pregnancies
and/or neonates with postnatal problems requiring higher-level care. The community birth centre within the region catered for around 250 deliveries per year. The deliveries here that were included were to low-risk women in whom there had been no complications of pregnancy. In addition, a proportion of the lowest-risk pregnancies were represented by deliveries at home.
Definition of geographical boundaries for recruitment
For the purposes of this study a geographical area covered by these hospitals was defined that maximised the number of participants in the study but minimised the number of residents who would deliver in other
units not participating in the study (Figure 8). The region covered by the study was well known to the
researchers and has previously been the setting for a number of successful population-based research studies.
Data were obtained from the ONS for the hospital of birth for babies born in 2007 to mothers living in the postcode areas NG (Nottingham) and LE (Leicester). Based on these data, for each postcode sector (e.g. LE1 6) the percentage of births delivering at the five maternity units participating in the study was calculated. A cut-off point was then determined for the minimum percentage of births to occur in the five participating maternity units that would give at least 85% of all births in the total included area occurring in these units, that is to say that a cut-off point of 85% would mean that at least 85% of all births in each included postcode sector would deliver at one of the five participating delivery sites. The percentage of
Derbyshire Derby Nottinghamshire Nottingham Lincolnshire Rutland Leicestershire Staffordshire Staffordshire Northamptonshire Leicester
all births in the included area delivering to those five sites was actually much higher than this cut-off point as nearly all women living in close proximity to a participating hospital deliver there.
Based on these estimates, and the aim of including around 2000 singleton infants in the study, a cut-off point of 85% was decided on. This equated to 96.8% of births for the included postcode sectors actually occurring in the five participating hospitals, increasing to 99.2% when home births were included: that is, only 0.8% of births occurred in maternity units other than the five participating in the study.
Sample size
The sample size was based on detecting differences in rates of cognitive impairment and early
rehospitalisation between the study and control groups of infants from singleton pregnancies. School-age
follow-up of children in the EPICure study used a group of classroom controls,136 among whom the rate of
cognitive impairment was 2%. There are no data for rates of cognitive impairment in moderately preterm infants in the UK. It was estimated that a rate of 5% cognitive impairment in our study group would be
clinically relevant and justify targeted intervention in children’s health and education services. Oddieet al.115
found that the rate of rehospitalisation in the first month of life in babies born at 35–37 weeks’gestation
was 6%, compared with 3% among term-born infants. A sample size estimation based on these figures predicted that recruitment of 800 singleton infants per group would allow detection of this difference in cognitive function with 90% power and in rehospitalisation with 80% power at the 5% significance level. To allow for potential non-consent and loss to follow-up, we decided to try to recruit 1000 singleton LMPT infants and 1000 singleton term-born infants.
In 2007, there were approximately 17,000 singleton births in the selected study area in Leicestershire and
Nottinghamshire. Assuming that the proportion of births at 32+0–36+6weeks’gestation is 6–7%, it was
anticipated there would be around 1000–1200 LMPT singleton births in 1 year. A minimum recruitment
rate of 80% would give the required sample size.
Multiple births
To ensure inclusion into the study of sufficient term-born infants from multiple pregnancies it was decided
to include all births at 32+0weeks’gestation or greater resulting from multiple pregnancies.
Selection of singleton control infants
Potential term-born control babies were identified using a pseudo-random sample of births obtained from ONS births data for 2007. For a random sample of 1000 births for the study area, ONS supplied
information on the day of the week of birth, month of birth and place of delivery. A date and time of birth were then assigned to each of the births in this sample using known dates and time for births in
Leicestershire obtained from the Child Health Registers for Leicester and Leicestershire and Rutland PCTs. These data were adjusted for day of the week to ensure an appropriate sampling of babies born at the weekend, as non-urgent induction of labour and CSs are more likely to be undertaken on a weekday.
This method overcomes the bias that may occur if more naive sampling methods are used, for example
selecting the next term birth to occur at the maternity unit after a LMPT birth.137,138Such sampling methods
would be likely to result in oversampling of high-risk term-born infants as these tend to be delivered in the sample places and at the same times as LMPT births; for example, no births would have been sampled from the midwifery-led unit.
Twelve births in the sample were excluded as they occurred at centres other than the five maternity units included in the Late And Moderately preterm Birth Study (LAMBS) or at home. Therefore, the 988 controls were used plus an additional 12 sampled from the 988 to make a pseudo-sample of 1000 controls. The list of potential control singleton births was then passed to the study midwives.
The birth to be included in the study was the first birth recordedat or afterthe time stated on the sample list. If there was uncertainty over which birth should be included because more than one birth occurred at the same time, then the NHS numbers of the mothers were examined and the infant included was the one born to the mother with the lowest final digit of NHS number. For example, if there were two eligible
births to mothers with NHS numbers 2365892145and 6523674352, then the mother with the latter
number would be included. If the last digits were identical, then the next digit to the left would be used until there was a difference.
Recruitment to Late And Moderately Preterm Birth Study
Timing of recruitment
We aimed to recruit both study and control infants during their initial hospital stay following delivery. The length of this stay varied considerably depending on the gestational age and clinical condition of the baby at birth and the condition of the mother. In all centres, it was common for term-born infants to be
discharged home at 6–12 hours following delivery if there was no medical indication for either mother or
baby to remain in hospital. Infants at the lower end of the gestational range required admission to a NNU and longer hospital stays.
At the time of recruitment, the mothers were either on the delivery suite or on a postnatal ward depending on the anticipated length of hospital stay. If any mother was too sick to give consent in the period following delivery, this process was delayed until the obstetrician caring for her was happy that she was in a fit condition to be approached for consent.
Identification of eligible mothers and infants
Clinical staff on the delivery suite of each participating hospital identified infants born at 32–36 weeks’
gestation and informed a member of the research team. The research midwives referred each day to the list of dates and times on which to base recruitment of the control infants in order to identify the next
infant born at≥37 weeks’gestation eligible to be recruited to the control group.
Consent
The Derbyshire NHS Research Ethics Committee (REC) approved the study design and methods. A team of six midwives who worked collaboratively across the centres carried out recruitment to the study. A research midwife attempted to approach all eligible mothers within the first 24 hours after the birth to provide them with an information sheet and obtain written informed consent for their participation. Mothers who were discharged before this initial contact could be made to present the study were contacted by a member of the clinical staff and, when possible, a home visit by a research midwife was arranged. The midwife obtained informed consent at this visit.
Written consent was obtained from parents of study and control infants for the following:
l interview with a research midwife and completion of a maternal lifestyle questionnaire
l collection, retention and analysis of pregnancy, perinatal and neonatal data