A comparison of the maternal levels of serum proprotein convertase subtilisin/kexin type 9 in pregnant women with the complication of fetal open neural tube defects

Abstract

It was aimed to evaluate the levels of maternal serum proprotein convertase subtilisin/ kexin type 9 (PCSK9) in pregnant women with a fetus diagnosed with open neural tube defects (NTDs). This case-control study included 38 pregnant women carrying fetuses with open NTDs and 44 age-matched, pregnant women with no specified risk factors.Comparisons were made of the groups in respect of demographic and clinical data and PCSK9 levels. To examine the performance of PCSK9 levels in the prediction of fetal open NTDs, receiver operating characteristic (ROC) curve analysis was used. In the first and second trimesters, PCSK9 levels were determined to be lower in the NTD group than in the control group (p = 0.010 and p = 0.015, respectively). In the first trimester, the lower PCSK9 levels in the NTD group were not statistically significant (p = 0.575). In the second trimester, the ROC curve value with the best balance of sensitivity/specificity for PCSK9 was 71.9 ng/ml (84.6% sensitivity, 51.7% specificity) and in the first and second trimester combined, 74.4 ng/ml (81.6% sensitivity, 45.5% specificity) (p = 0.015, p = 0.036, respectively). PCSK9 may be involved in the etiopathogenesis of open NTDs at the critical steps of fetal neuronal differentiation. Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs.

Risk Factors of Anencephaly: A Case–Control Study in Dessie Town, North East Ethiopia

“…Although it has limitations, PCSK9 may be used as an additional biomarker for the screening of NTDs. 6 Several studies have reported various risk factors linked to anencephaly, which include socioeconomic status, parental education, maternal age and occupation, smoking, alcoholism, maternal reproductive history, infection during early pregnancy, diabetes, obesity, and maternal use of caffeine and medications during early pregnancy. [7][8][9] The prevalence of anencephaly shows great variation among different countries, with 12 per 10,000 births in Iran, 10 10.4 per 10,000 births in China, 0.00-7.42 per 10,000 births in Rijeka, Croatia, 11 0.5-0.6 per 1000 live births in Singapore 12 and 0.5-6.5 per 1000 live births in India.…”

PCSK9 inhibitor cooperatively with high triglyceride induces adverse pregnancy outcomes by impairing mitochondrial function

“…Notably, the safety of using PCSK9i during pregnancy is yet to be clearly established, particularly as PCSK9i has been shown to cross the placental barrier (18). Our prior research as well as a recent study identi ed lower PCSK9 expression in the serum of pregnant women with NTD fetuses (12,15), assuming that NTDs could be possible side effects among pregnant women exposed to PCKS9i. However, there is no evidence to manifest the safety of PCSK9i with regard to foetal NTDs.…”

“…NTDs, which occur following failure of neural tube closure during the fourth week of embryonic development, are among the most common and devastating congenital anomalies of the central nervous system (13). Typical NTDs include spina bi da, anencephaly, and exencephaly, according to the location and severity of the lesion, which pose huge medical, nancial, and psychological costs on affected families (14).. A more recent study con rmed that reduced PCSK9 in maternal serum is a potential biomarker for human pregnancies with open NTDs (15). PCSK9 is expressed in the brain at certain crucial stage during embryonic neurulation, which is a key time point in NTD formation (2,16,17).…”

Non-Isolated Neural Tube Defects with Comorbid Malformations Are Responsive to Population-Level Folic Acid Supplementation in Northern China

“…A previous epidemiological study of NTDs also showed that isolated NTDs were more sensitive to environmental factors, whereas non-isolated NTDs were sensitive to both environmental and genetic factors [ 30 ]. In addition, some biomarkers are also considered to play an important role in NTD screening during pregnancy, such as maternal serum alpha-fetoprotein (MSAFP) [ 31 ] and proprotein convertase subtilisin/kexin type 9 (PCSK9) [ 32 ]. However, whether the same biomarkers are equally predictive for screening isolated NTDs and non-isolated NTDs needs further research.…”