Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study

Calculation of gestational age

Gestational age in weeks was calculated on the basis of the mother’s report of her expected due date. In the MCS, this corresponded well with routine hospital records of gestational age.¹⁶ We divided gestational age at birth into very preterm (23-31 weeks), moderate preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), and full term (39-41 weeks). We excluded post-term infants (42-43 weeks) because preterm and post-term birth are known to have different causes and because comparison with hospital data showed that post-term birth was prone to misclassification in our study.¹⁶ We identified implausible combinations of birth weight and gestational age as those that were larger or smaller than the median plus or minus twice the interquartile range, using birth weight for gestational age centiles as reported by Bonellie et al.¹⁷ In cases of maternal diabetes, we considered birth weights over these limits to be plausible. These steps excluded 97 observations.

Health outcomes

Height, weight, and body mass index were assessed at 3 and 5 years. Trained interviewers measured height with a Leicester stadiometer and recorded it to the nearest completed millimetre. They measured weight without outdoor clothes or shoes by using Tanita HD 305 scales and recorded it in kilograms to one decimal place. Children were categorised as underweight, normal weight, overweight, or obese according to age and sex specific cut-offs for body mass index.^{18 19}

Parental reports of the number of hospital admissions not related to accidents since birth or the previous interview were collected at 9 months and at 3 and 5 years. Parental reports of any longstanding illness, disability, or infirmity of more than three months’ duration and diagnosed by a health professional were collected at 3 and 5 years. We defined limiting longstanding illness as illness that limited activities normal for the child’s age group. Parental reports of wheezing within the previous 12 months and asthma were collected at 3 and 5 years. Parental reports of the use of prescribed drugs, coded according to the British National Formulary were collected at 5 years. Parents’ ratings of children’s health as excellent, very good, good, fair, or poor were collected at 5 years.

Statistical methods

We restricted analyses to births for which the natural mother was the respondent at the 9 month interview. We modelled binary outcomes by using logistic regression and continuous outcomes by using linear regression with the full term group as the reference. All analyses accounted for multiples by adjusting for multiple birth status as a linear regression term and allowing for clustering by family. We adjusted analyses for the child’s sex, ethnicity (white British, Indian, Black Caribbean/Black African, Bangladeshi/Pakistani, other), and age at interview; for mother’s education (academic degree, completed high school, completed basic compulsory school, overseas qualifications, no formal qualifications), marital status (married, cohabiting, single), occupation (managerial/professional, intermediate, self employed/small employer, lower supervisory/technical occupations, routine/semi-routine, long term unemployed), and age at delivery; birth order; duration of breast feeding; and maternal smoking (non-smoker, stopped smoking during pregnancy, smoked throughout pregnancy) and alcohol intake (never, moderate (not more than 3-6 units per week or 3-5 units per occasion), heavy (≥7 units per week or ≥6 units per occasion)) during pregnancy.

We estimated population attributable fractions associated with preterm and early term birth as (proportion of cases exposed)×(OR−1)/OR, where OR is the adjusted odds ratio from the logistic model. We calculated approximate 95% confidence intervals for population attributable fractions by using the Bonferroni inequality method.²⁰ All analyses allowed for the clustered, stratified sample design by using the “survey commands” in Stata version 11. All reported percentages and means are weighted according to sampling design and non-response.^{21 22}

Growth and weight gain

Height and weight decreased across gestational age groups with increasing prematurity, and this effect was present at both 3 and 5 year assessments (table 3​3).). We also found several differences between specific gestational age groups. Figure 2​2 shows the classification of body mass index by gestational age. At 3 and 5 years, the highest proportion of children classified as obese was in the late preterm group. Children born very preterm were most likely to be classified as underweight at both 3 and 5 years.

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Fig 2 Classification of weight status according to body mass index at 3 and 5 years for gestational age groups

General health status

Measures of general health, hospital admissions, and longstanding illness showed similar patterns. A gradient of increasing risk of poorer outcomes with increasing prematurity extended across the range of gestational age groups (tables 4​4 and 5​5).). With respect to the first nine months of life, the most common primary reasons for admission to hospital were respiratory disorders, including chest infection and wheezing or asthma; gastrointestinal disorders, including gastroenteritis and gastro-oesophageal reflux; and viral illness or fever. The proportion of infants admitted to hospital for chest infections increased with increasing prematurity (data not shown). For all general health measures, the odds ratios associated with moderate and late preterm and early term birth were smaller than those associated with very preterm birth, but the number of children with health problems was much larger for children born at moderate and late preterm or early term. The population attributable fractions associated with moderate/late preterm and early term birth were larger than those for very preterm birth: 5.7% and 7.2% compared with 3.8% for having at least three hospital admissions between 9 months and 5 years, 7.7% and 0.2% compared with 3.2% for limiting longstanding illness at 3 years, and 5.4% and 5.4% compared with 2.7% for limiting longstanding illness at 5 years.

Parents’ subjective rating of their children’s health at 5 years of age also broadly reflected a similar pattern. Children’s health was more likely to be perceived as poor with increasing degrees of prematurity (table 6​6).

Strengths and limitations of study

This study represents the first data for health outcomes across the full range of gestational age groups for babies born this century. A major strength of the study is that the data are representative of the UK population. Data collection included multiple health measures providing a broad range of information on children through infancy and childhood and allowing adjustment for potential confounding factors known to affect children’s health and development. The study also benefited from oversampling of socially disadvantaged areas and non-response weighting to allow for differential participation and dropout.

A limitation of the study is that gestation was estimated according to maternal report. Agreement between maternal report and hospital records was 94% for gestation plus or minus one week.¹⁶ This method may result in some misclassification, however, although this is less problematic when data are used in groups. A further limitation is the study’s reliance on parental report of children’s health status, without verification of data by use of medical records. With the exception of anthropometric data, parents provided information on all outcomes. This method is prone to potential recall bias, which may lead to under-reporting or over-reporting of outcomes. However, studies have shown that parental report of episodes of acute illness and healthcare correlates well with medical records.^{24 25} Bias and overestimation of effects may potentially have been introduced if worried parents of sick children tended to respond more frequently than those whose children remained well; lack of detailed information about severity of illness is a further weakness. Conversely, children admitted to hospital more than three times during the first nine months had disproportionately high dropout at 3 and 5 years, which may lead to underestimation of adverse outcomes at later follow-up.

Comparison with other studies

Interest in outcomes for more mature preterm babies has increased recently, following publication of work showing a higher risk of mortality and morbidity in babies of 32-36 weeks’ gestation compared with those born at 37 weeks or later.^{4 6} In terms of readmission to hospital, previous research has focused mainly on the first year of life and has found that late preterm babies required readmission during the first months of life more often than did those born at 37 weeks or later.^{26 27 28} Similarly, Bird et al showed increased healthcare use and costs in the first year associated with late preterm birth compared with babies of at least 37 weeks’ gestation.²⁹ Our data enabled us to examine admissions up to 5 years of age and also in less mature babies, and we showed a similar gradient of risk. When interpreting such findings, it is important to remember that the initial neonatal stay, particularly in very preterm babies, may be prolonged, thereby reducing the opportunity for readmission during the first months of life. However, we saw a similar pattern across gestational age groups for admissions to hospital between 9 months and 5 years. When considering types of morbidity, McLaurin et al found that, in infants born at 33-36 weeks of gestation, respiratory and gastrointestinal disorders accounted for half of the admissions.²⁷ Our results were consistent with this and also showed an increased risk of asthma and wheeze in these infants compared with infants born at term. In contrast, Abe et al were unable to show a significant association between late preterm birth and risk of developing asthma.³⁰

Implications for policy and service provision

In the absence of data from prospective studies specifically focusing on moderate preterm, late preterm, and early term birth, this study provides information on the effect of gestation at birth on use of healthcare services to inform planning and provision of future healthcare for infants and children. The findings also, of course, have implications for obstetricians managing high risk pregnancies.

Research and resources have, in recent years, been directed towards very preterm babies who are at the highest risk of neonatal morbidity and poor outcomes. However, this small group of babies (approximately 8000 births annually in England) is far outnumbered by more mature preterm babies, born at 32-36 weeks.² This group has been understudied until recently, and babies of this gestation, although immature, have been considered to be at minimally greater risk of adverse outcomes than babies born at 37 weeks or later. Even less well understood are the risks associated with birth at 37-38 weeks (125 000 births annually²), as this has been thought to represent term gestation. Our study casts doubt on these perceptions and highlights differences between these babies, now more appropriately classed as early term, and those born just one or two weeks later. In interpreting our results, we acknowledge that the groups may differ for reasons other than simply gestation at birth. Significant obstetric concerns in late pregnancy commonly lead to induction or caesarean section before full term, and the early term group is thus likely to contain infants who might be predicted to have a poorer outcome by virtue of intrauterine compromise, rather than prematurity itself. In our study, data were not available on the indications for delivery. Nevertheless, irrespective of the reason for delivery, large numbers of relatively mature babies who are potentially at risk means that, although their problems are subtler than those of very preterm babies, they are more numerous and therefore likely to present a greater burden for health and education services.

Advances in neonatal and obstetric care have led to increasing survival and improved short term outcomes at all preterm gestations. This, in turn, has led to increased confidence both in prolongation of complicated pregnancies at very preterm gestations and in early intervention with delivery for problems at later stages in pregnancy but before full term has been reached. This, together with the influence of greater maternal choice regarding timing of delivery, has led to increasing numbers of babies born at 32-38 weeks of gestation. The findings of our study and others should prompt exploration of obstetric decision making processes at moderate preterm, late preterm, and early term gestations.