Alkaline phosphatase of late pregnancy promotes the prediction of adverse birth outcomes

Abstract

Background: Adverse birth outcomes (ABO), such as preterm birth (PTB), small and large for gestational age (SGA/LGA), can compromise both the short- and long-term health of mothers and their foetuses. The purpose of this observational study was to investigate the association between maternal serum alkaline phosphatase (ALP) levels in late pregnancy and the risk of ABO, and to evaluate its predictive value of maternal ALP levels for ABO in women with singleton pregnancies.

Methods: A total of 11 853 consecutive pregnant women underwent hepatic and renal function tests, lipid profile assessments, ALP and high-sensitivity C-reactive protein levels measurements upon admission for labour. Their clinical perinatal parameters and outcomes were also analysed.

Results: The prevalence of PTB, SGA, and LGA in this study was 7.2% (n = 849), 8.9% (n = 1053), and 15.6% (n = 1844), respectively. With increasing quartiles of maternal serum ALP levels, the foetal gestational age increased by 0.58 weeks (95% confidence interval (CI) = 0.50-0.66), 0.78 weeks (95% CI = 0.70-0.86), and 0.98 weeks (95% CI = 0.90-1.06), respectively, and the birth weight increased by 62.91 g (95% CI = 43.96-81.86), 91.54 g (95% CI = 72.41-110.67), and 117.92 g (95% CI = 98.18-137.67), respectively. Compared to women in the bottom quartile of ALP, those in the top quartile had a lower risk of PTB (adjusted odds ratio (OR) = 0.14; 95% CI = 0.11-0.18), a lower risk of SGA (adjusted OR = 0.65; 95% CI = 0.53-0.80), and a higher risk of LGA (adjusted OR = 1.92; 95% CI = 1.62-2.28). Sensitivity analyses conducted among individuals without advanced maternal age, obesity, multiparity, pregnancy complications, and PTB (for SGA/LGA) validated the consistency of these results. More importantly, adding ALP to the established model significantly increased the area under the curve (AUC) for predicting adverse birth outcomes: for PTB, the AUC increased from 0.761 to 0.809 (P < 0.001); for SGA, it increased from 0.754 to 0.759 (P = 0.014); and for LGA, it increased from 0.750 to 0.755 (P < 0.001).

Conclusions: Maternal serum ALP levels in late pregnancy are significantly associated with the risk of ABO. When combined with clinical characteristics and routine laboratory results, ALP has incremental predictive value for ABO, particularly for PTB.

Figure 1

Receiver operating characteristic (ROC) curves to appraise the performance of different variables and models in predicting PTB and SGA/LGA. Panel A. PTB. Panel B. SGA. Panel C. LGA. Panel D. PTB. Panel E. SGA. Panel F. LGA. Model 1: maternal age, height, weight, gravidity, parity, blood BP, pregnancy complications, assisted reproduction, foetal sex, blood lipids, liver and kidney function and hs-CRP. Model 2: Model 1 plus ALP. ALP – alkaline phosphatase, AUC – area under the curve, BP – blood pressure, hsCRP – high sensitive C-reactive protein, LGA – large for gestational age, PTB – preterm birth, SGA – small for gestational age.