Date Published: January 31, 2017
Publisher: Public Library of Science
Author(s): Stamatina Iliodromiti, Daniel F. Mackay, Gordon C. S. Smith, Jill P. Pell, Naveed Sattar, Debbie A. Lawlor, Scott M. Nelson, Jenny E Myers
Abstract: BackgroundThere is limited evidence to support the use of customised centile charts to identify those at risk of stillbirth and infant death at term. We sought to determine birth weight thresholds at which mortality and morbidity increased and the predictive ability of noncustomised (accounting for gestational age and sex) and partially customised centiles (additionally accounting for maternal height and parity) to identify fetuses at risk.MethodsThis is a population-based linkage study of 979,912 term singleton pregnancies in Scotland, United Kingdom, between 1992 and 2010. The main exposures were noncustomised and partially customised birth weight centiles. The primary outcomes were infant death, stillbirth, overall mortality (infant and stillbirth), Apgar score <7 at 5 min, and admission to the neonatal unit. Optimal thresholds that predicted outcomes for both non- and partially customised birth weight centiles were calculated. Prediction of mortality between non- and partially customised birth weight centiles was compared using area under the receiver operator characteristic curve (AUROC) and net reclassification index (NRI).FindingsBirth weight ≤25th centile was associated with higher risk for all mortality and morbidity outcomes. For stillbirth, low Apgar score, and neonatal unit admission, risk also increased from the 85th centile. Similar patterns and magnitude of associations were observed for both non- and partially customised birth weight centiles. Partially customised birth weight centiles did not improve the discrimination of mortality (AUROC 0.61 [95%CI 0.60, 0.62]) compared with noncustomised birth weight centiles (AUROC 0.62 [95%CI 0.60, 0.63]) and slightly underperformed in reclassifying pregnancies to different risk categories for both fatal and non-fatal adverse outcomes (NRI -0.027 [95% CI -0.039, -0.016], p < 0.001). We were unable to fully customise centile charts because we lacked data on maternal weight and ethnicity. Additional analyses in an independent UK cohort (n = 10,515) suggested that lack of data on ethnicity in this population (in which national statistics show 98% are white British) and maternal weight would have misclassified ~15% of the large-for-gestation fetuses.ConclusionsAt term, birth weight remains strongly associated with the risk of stillbirth and infant death and neonatal morbidity. Partial customisation does not improve prediction performance. Consideration of early term delivery or closer surveillance for those with a predicted birth weight ≤25th or ≥85th centile may reduce adverse outcomes. Replication of the analysis with fully customised centiles accounting for ethnicity is warranted.
Partial Text: Infants who are born at the extremes of birth weight have a higher risk of adverse perinatal outcome . In developed countries, one-third of stillbirths and infant deaths occur at term , yet no consensus exists about what defines a small or large fetus or infant at term. A variety of methods have been used, including absolute birth weight (most commonly <2,500 g and >4,000 g or 4,500 g), or statistical thresholds outside the expected birth weight for gestational age (commonly <10th or >90th centile or, for more severe phenotypes, two standard deviations) [3–7]. Whether these thresholds optimally define the risk of perinatal mortality and morbidity at term is unknown. Furthermore, some advocate that birth weight percentiles should account for maternal characteristics known to be associated with fetal growth, such as weight, height, parity, and ethnicity. However, there is conflicting evidence whether customised charts perform better than noncustomised centiles in predicting adverse perinatal outcome [8–11] and the strength of evidence for supporting this approach, particularly for term infants, has been challenged [12,13].
The Privacy Advisory Committee of the Information Services Division (ISD) of the National Services Scotland awarded ethical approval for access to and linkage of the datasets (www.isdscotland.org). All data were nonidentifiable, and individual informed consent from participants was not required.
Being born too small or too large is associated with an increased risk of mortality and morbidity [1,5,7]. Despite dramatic improvements in maternal and neonatal care, we showed that even at term (37 to 43 gestational weeks) birth weight remains strongly associated with the risk of stillbirth and infant death, low Apgar score, and admission to the neonatal unit. An increased risk of mortality and morbidity was evident at term with birth weights ≤25th and ≥85th centile irrespective of whether noncustomised or partially customised centiles were used, with similar associations observed for potentially preventable infant deaths due to anoxia, trauma, or intracranial haemorrhage. These thresholds may not apply to diabetic pregnancies, in which there is evidence of increasing mortality with greater birth weight. Given that partially customised centiles exhibited weaker associations with mortality than simpler noncustomised centiles, their increasingly wide adoption by health care providers  for identifying may not be appropriate for assessing risks of adverse perinatal outcome at term.