Old Question Revisited: Are High-Protein Diets Safe in Pregnancy?

Background: A previous randomized dietary intervention in pregnant women from the 1970s, the Harlem Trial, reported retarded fetal growth and excesses of very early preterm births and neonatal deaths among those receiving high-protein supplementation. Due to ethical challenges, these findings have not been addressed in intervention settings. Exploring these findings in an observational setting requires large statistical power due to the low prevalence of these outcomes. The aim of this study was to investigate if the findings on high protein intake could be replicated in an observational setting by combining data from two large birth cohorts.
Methods: Individual participant data on singleton pregnancies from the Danish National Birth Cohort (DNBC) ( n = 60,141) and the Norwegian Mother, Father and Child Cohort Study (MoBa) ( n = 66,302) were merged after a thorough harmonization process. Diet was recorded in mid-pregnancy and information on birth outcomes was extracted from national birth registries.
Results: The prevalence of preterm delivery, low birth weight and fetal and neonatal deaths was 4.77%, 2.93%, 0.28% and 0.17%, respectively. Mean protein intake (standard deviation) was 89 g/day (23). Overall high protein intake (>100 g/day) was neither associated with low birth weight nor fetal or neonatal death. Mean birth weight was essentially unchanged at high protein intakes. A modest increased risk of preterm delivery [odds ratio (OR): 1.10 (95% confidence interval (CI): 1.01, 1.19)] was observed for high (>100 g/day) compared to moderate protein intake (80-90 g/day). This estimate was driven by late preterm deliveries (weeks 34 to <37) and greater risk was not observed at more extreme intakes. Very low (<60 g/day) compared to moderate protein intake was associated with higher risk of having low-birth weight infants [OR: 1.59 (95%CI: 1.25, 2.03)].
Conclusions: High protein intake was weakly associated with preterm delivery. Contrary to the results from the Harlem Trial, no indications of deleterious effects on fetal growth or perinatal mortality were observed.