Discussion

Main Findings

In a large, population-based cohort study, we compared the impact of using growth standards with a common centile cutoff across the gestational week (‘week’ charts) vs growth standards applying a unique centile cutoff for each gestational day (‘day’ charts). Using week charts, we found that an infant was almost half as likely to be considered <10th centile if born at the beginning of the week (+0 days) compared with the end (+6 days). In relative terms, this meant 21% fewer infants were <10th centile at +0 days, and 28% more at +6 days, highlighting a substantial reclassification These same findings were demonstrated for those classified <3rdcentile – the cohort most likely to be subject to obstetric interventions based purely on size (30). Importantly, whether day or week charts were used then impacted the relative risk of stillbirth amongst small for gestational age infants born at +0 days and +6 days.
When week charts were used, the <10thcentile proportion was highest at +0 days, but the relative risk of stillbirth lowest. This suggests that the SGA cohort at the beginning of the week has been diluted by small, healthy infants, that have not yet had the benefit of the seven-day period in which to grow. When day charts were used, and equivalent proportions were considered SGA, no significant differences in stillbirth risk were seen between +0 days and +6 days. This suggests that a measurable misclassification is occurring when week charts are used, which is corrected by using day charts.
The magnitude of these classification differences in SGA has important clinical implications for those infants born, or measured, at the extremes of a gestational week. If an infant is identified as <10th, and particularly <3rd centile, it is treated as increasing the pre-test probability of that infant having true fetal growth restriction (31). Fetal weight centile therefore forms an important part of all antenatal surveillance regimes, including decisions regarding time and mode of birth (32, 33). Thus, it is important that the classification of smallness is applied consistently across the gestational week and correlates with perinatal risk. If an infant is born at 37 weeks +6 days, the likelihood of that infant being considered <10th centile should not be half that of if it was born a single day later, at 38 weeks +0 days, with the risk of stillbirth- if small- altered by almost 50%.

Strengths and limitations

The large size of our statewide cohort has allowed us to robustly assess the impact of using day specific growth standards on the detection of FGR and its most important obstetric outcome, stillbirth. As the first study to directly quantify the impact on stillbirth of using day charts over week charts, our findings make a useful contribution to the field by proposing a simple and effective way to improve classification of fetuses at risk. Our study is limited by its retrospective design, and by the need to exclude cases that did not have gestation in days available. However, there is no reason to suspect this missing data would have been unequal between groups, and it is therefore unlikely to have impacted the results. Another limitation is that we were only able to apply growth standards to a population of infants already born. This means that we are only able to hypothesise about the potential benefit of adjusting growth standards to day-specific cutoffs on antenatal management decisions, informed by ultrasound estimated fetal weights.

Interpretation

There is considerable debate about which growth standard should be used to define size in obstetric practice (20). Many aspects of growth standards are highly controversial such as customisation on maternal characteristics (34, 35), with unresolved debate regarding which physiological characteristics have likely pathological influences on fetal growth. Here, we have instead focussed on providing evidence of benefit for one specific aspect of growth standards- the use of ‘day’, rather than ‘week’ -charts, which appear to more accurately classify fetal risk in both the clinical and research settings.
Although many contemporary growth standards do provide the option for an individual centile for each gestational day (34, 36-38), others rely only on a single set of centiles for each completed week. Several international charts in use (23, 39), and the standards currently used in Australia for postnatal birthweight classification (22, 40), provide only a centile cutoff for each week. This means many clinicians still receive ultrasound or birthweight reports derived from a single weekly centile cutoff. Our findings provide strong evidence that the timing within a gestational week of when the infant was measured needs to be taken into consideration when interpreting the findings. Moreover, for many years, there has been increasing concern about the high rates of obstetric intervention and the potential for iatrogenic harm (41-43). Here, we provide a simple method by which SGA classification can be improved to correlate better with perinatal outcomes without inflating the proportion of pregnancies considered at risk.