Inflammatory markers in pregnancy – a prospective longitudinal study
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Background: The role of inflammation in the pathogenesis of adverse pregnancy outcomes for both mother and child is no longer disputed. Several of these processes are related to fetal growth. Neopterin and kynurenine-tryptophan ratio (KTR) are both known to be increased in cellular immune responses. During pregnancy an increased KTR is also thought to induce immunotolerance in the mother, promoting normal fetal development and growth. A third biomarker, 25‐hydroxyvitamin D (25-OH-D), may be related to fetal growth by immunological properties of its active metabolite 1,25-dihydrokxyvitamin D (1,25-(OH)2-D), as well as through direct effects of vitamin D on fetal growth. Material and methods: This study was based on a sample of 92 para 1 and 2 women, of whom 61 % had a definite increased risk for a small for gestational age (SGA) birth. Serial blood samples at gestational weeks 17, 33 and 37 of pregnancy were analysed together with concurrent ultrasound examinations in gestational weeks 25, 33 and 37. Neopterin, KTR and 25-OH-D were investigated regarding their potential to predict fetal growth and adverse birth outcomes. Outcomes were growth deviation at the time of, and the variability in growth deviation between, the ultrasound examinations, as well as birth weight, ponderal index and placental weight. Covariates included maternal age, body mass index (BMI), smoking after gestational age 33, parity, fetal gender and gestational age at the time of blood sampling and ultrasound examination. Statistical analyses utilized included appropriate univariate analyses and multiple linear regression. Results: Neopterin and KTR increased significantly during pregnancy (p = 0.000), while levels of 25-OH-D remained stable. Serum levels of 25-OH-D in week 17 were able to predict a negative growth deviation in week 33 and 37, as well as difference in growth deviation from week 25 to 37. Associations of 25-OH-D to birth weight showedborderline significance (p = 0.058) and serum levels in gestational week 17 were on average 17.49 nmol/L (95 % CI 5.75-29.23, p = 0.004) lower among those women who later gave birth to an SGA infant. Neopterin was associated with concurrent growth deviation in week 33 (p = 0.002). Neither neopterin nor KTR could prospectively predict fetal growth deviation or birth outcome. Moreover, none of the three biomarkers could predict ponderal index of the newborn or placental weight. An exception was a negative relation between 25-OH-D measured in week 37 and index. Interpretation: Our study indicated that 25-OH-D measured early in pregnancy is a usefull marker to predict growth from gestational age 33 of pregnancy, as well as birth weight, in para 1 and para 2 mothers. Neopterin and KTR measured in week 33 and 37 may be used to indicate risk of concurrent and previous growth deviation, however no prospective predictive potential was found.