Date Published: September 20, 2019
Publisher: Public Library of Science
Author(s): Matias C. Vieira, Sophie Relph, Martina Persson, Paul T. Seed, Dharmintra Pasupathy, Gordon C Smith
Abstract: BackgroundAlthough many studies have compared birth-weight charts to determine which better identify infants at risk of adverse perinatal outcomes, less attention has been given to the threshold used to define small or large for gestational age (SGA or LGA) infants. Our aim was to explore different thresholds associated with increased risk of adverse perinatal outcomes using population, customised, and Intergrowth centile charts.Methods and findingsThis is a population-based cohort study (Swedish Medical Birth Registry), which included term singleton births between 2006 and 2015 from women with available data on first-trimester screening. Population, customised, and Intergrowth charts were studied. Outcomes included cesarean section, postpartum haemorrhage, severe perineal tear, Apgar score at 5 minutes, neonatal morbidity, and perinatal mortality. Odds for each outcome were assessed in intervals of 5 centiles of birth weight (reference being 40th–60th centiles) using logistic regression. Intervals of 5% of the population were also explored. Sensitivity for fixed false-positive rates (FPRs) was reported for neonatal outcomes. Data from 212,101 births were analysed. Mean age was 33 ± 5 years, 48% of women were nulliparous, and 80% were born in Sweden. Prevalence of SGA (<10th centile) was 10.1%, 10.0%, and 3.1%, and prevalence of LGA (>90th centile) was 10.0%, 8.2%, and 25.1%, assessed using population, customised, and Intergrowth charts, respectively. In small infants, the risk of perinatal mortality was consistently increased below the 15th, 10th, and 35th birth-weight centiles for the respective charts (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.05–2.39, p = 0.03 for 10th–15th population centile; OR 2.54, 95% CI 1.74–3.71, p < 0.001 for 5th–10th customised centile; OR 1.81, 95% CI 1.07–3.04, p = 0.03 for 30th–35th Intergrowth centile). The strength of association with adverse perinatal outcomes was different between infants below the 5th birth-weight centile for each chart (OR 4.47, 95% CI 3.30–6.04, p < 0.001 for the population chart; OR 5.78, 95% CI 4.22–7.91, p < 0.001 for the customised chart; OR 10.74, 95% CI 7.32–15.77, p < 0.001 for the Intergrowth chart) but similar in the smallest 5% of the population (OR 4.34, 95% CI 3.22–5.86, p < 0.001 for the population chart; OR 5.23, 95% CI 3.85–7.11, p < 0.001 for the customised chart; OR 4.69, 95% CI 3.47–6.34, p < 0.001 for the Intergrowth chart). For a fixed FPR of 10%, different thresholds for each chart achieved similar sensitivity for perinatal mortality in small infants (29% for all charts). Similar behaviour of different thresholds and similar risk/sensitivity for fixed FPR were observed in relation to other outcomes and for LGA infants. Limitations of this study include the relative homogeneity of the Swedish population, which limits generalisability to other populations; customised centiles may perform differently in populations with increased heterogeneity of ethnic background.ConclusionsThe risk of adverse outcomes was consistent across proportions of the population but did not reflect fixed thresholds, such as the 10th or 90th centiles, across different growth charts. Chart-specific thresholds for the population should be considered in clinical practice.
Partial Text: Infants with abnormal fetal growth have an increased risk of adverse perinatal outcomes [1–3]. Both small for gestational age (SGA) and large for gestational age (LGA) infants face excess risk of perinatal mortality and morbidity [3–5]; they are also at increased risk of long-term consequences including childhood obesity and metabolic disease later in life [6,7].
Amongst 233,379 women that met the inclusion criteria, 212,101 (90.9%) were part of our study population (Fig 1). The mean age of this cohort was 33 ± 5 years, 48% of women were nulliparous, and 80% were born in Sweden. The mean birth weight was 3,594 ± 478 g. Detailed demographic characteristics and pregnancy outcomes in the study population are provided in Table 3. A breakdown of neonatal morbidity composite is provided in S1 Table. Fracture and brachial plexus injury accounted for more than one-third of neonatal morbidities.
Our findings have advanced the debate on the choice of growth charts in clinical practice by acknowledging shifts in birth-weight distribution of the study population in relation to the reference population used to develop each chart, recognising the need for chart-specific thresholds to identify pregnancies at similar risk. This is imperative because ORs and sensitivities are not directly comparable if there is a difference in the FPR. Researchers and clinicians need to agree on what equates to a clinically meaningful increase in the risk of adverse outcomes and an acceptable FPR (or NNT) so that studies can further refine the most appropriate threshold for defining SGA and LGA.