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Beyond cut-offs: gestational age-specific perinatal mortality across the birthweight-for-gestational-age continuum-a
Liset Hoftiezer1,2,3, Michel H P Hof4, Richard A van Lingen5
1Department of Neonatology, Amalia Children's Hospital, Radboudumc Graduate School, Radboud University Medical Centre, Nijmegen, The Netherlands. liset.hoftiezer2@slingeland.nl.
Insights
Perinatal mortality risk changes gradually with birthweight and gestational age, not at fixed small (SGA) or large (LGA) for gestational age thresholds. These findings suggest current definitions may not accurately reflect continuous risk gradients.
Area of Science:
- Perinatal health
- Fetal growth
- Neonatal outcomes
Background:
- Small (SGA) and large (LGA) for gestational age infants have increased risks.
- Fixed SGA/LGA thresholds are rarely updated despite population changes and evolving clinical management.
Purpose of the Study:
- To characterize perinatal mortality across continuous birthweight-for-gestational-age (BW-for-GA) and gestational age (GA).
- To describe GA-specific mortality gradients instead of defining new SGA/LGA cut-offs.
Main Methods:
- Analysis of 2,581,816 singleton births in the Netherlands (2000-2015).
- Logistic regression modeling of perinatal mortality (fetal or early neonatal death) based on continuous GA and BW-for-GA percentile.
- Rate ratios calculated relative to the 50th percentile and GA-specific nadir.
Main Results:
- Perinatal mortality declined gradually with GA, with a nadir at 40 weeks.
- Mortality was lowest at the 80th-83rd BW-for-GA percentile and increased at both extremes.
- Infants below the 3rd percentile had at least double the mortality risk compared to the median.
Conclusions:
- Perinatal mortality exhibits continuous, graded patterns across BW-for-GA and GA.
- Rigid SGA and LGA thresholds have limitations in reflecting true, continuous risk.
- Nuanced interpretation of risk is supported for clinical decision-making.
Abstract:
Abnormal fetal growth is linked to increased perinatal morbidity and mortality. Birthweight percentiles-commonly the 10th and 90th-define small (SGA) and large for gestational age (LGA) infants. Although birthweight charts are periodically updated, cut-offs for SGA and LGA remain fixed, despite changes in population characteristics and evolving clinical management. We aimed to characterize how perinatal mortality varies continuously across birthweight-for-gestational-age (BW-for-GA) and gestational age (GA), describing GA-specific mortality gradients rather than defining new cut-offs. We analyzed 2,581,816 singleton infants born in the Netherlands (2000-2015), excluding congenital malformations, extreme birthweights, or missing data. Perinatal mortality was defined as fetal or early neonatal death (< 7 days). Logistic regression modeled mortality based on continuous GA and BW-for-GA percentile, with rate ratios calculated relative to the 50th percentile and GA-specific nadir. Sensitivity analyses excluded antepartum stillbirths. Perinatal mortality declined gradually with GA, reaching a nadir at 40 weeks. Across BW-for-GA, mortality was lowest at the 80th-83rd percentile and higher at both extremes. Infants below the 3rd percentile had at least a twofold increase in mortality compared with those at median birthweight, while comparable increases for infants below the 10th percentile were observed only after 37 weeks. Sensitivity analyses excluding antepartum stillbirths reduced overall mortality but preserved the curvilinear pattern.
Conclusion:
Perinatal mortality varies continuously, without discrete inflection points, revealing graded, gestational-age-specific patterns across the population and highlighting the limitations of rigid SGA and LGA thresholds.
What Is Known:
• SGA and LGA infants face higher risks of adverse outcomes. • Although birthweight charts are regularly updated, fixed percentile cut-offs such as SGA and LGA are rarely reconsidered despite changing populations and evolving clinical management.
What Is New:
• Perinatal mortality varies continuously across birthweight-for-gestational-age, without discrete inflection points, revealing graded, GA-specific patterns. • This highlights the limitations of fixed SGA/LGA percentile thresholds and supports nuanced interpretation of risk for clinical decision-making.
