Are serum levels of inhibin A in second trimester predictors of adverse pregnancy outcome?

Yue, Chaoyan; Zhang, Chunyi; Ni, Yuan; Ying, Chunmei

doi:10.1371/journal.pone.0232634

Cited by 11 publications

(19 citation statements)

References 25 publications

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“…reported a significant association between high inhibin levels and medically indicated preterm birth. This observation was also noted by other studies, 12,46 which concluded that the relationship between preterm birth and inhibin was secondary to other placenta‐mediated complications that may increase the risk of elective or emergency premature delivery.…”

Section: Discussionsupporting

confidence: 79%

“…Recent literature supports an association between low levels of uE3 and adverse outcomes such as fetal growth restriction and spontaneous abortion 8 . A relationship also exists between high levels of inhibin and both pre‐eclampsia and preterm delivery, 12 whereas low inhibin in the first trimester has been associated with non‐viable pregnancies 13,14 …”

Section: Introductionmentioning

confidence: 97%

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Second trimester maternal serum biomarkers and the risk of cerebral palsy

et al. 2021

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Aims To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels. Method In this retrospective case–control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (n = 1290). We compared mean and abnormal levels of alpha‐fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β‐hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Results Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; p < 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p < 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p < 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight. Interpretation Abnormal second‐trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 97%

Second trimester maternal serum biomarkers and the risk of cerebral palsy

et al. 2021

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“… 21 Previous studies have reported that an increase of inhibin A is associated with adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, and preterm birth. 22 23 In contrast, there is limited information on the association between congenital malformation and an increased level of inhibin-A. 23 This study found an association between maternal serum inhibin-A in the second trimester with major fetal CHDs, but not with overall fetal cardiac defects.…”

Section: Discussionmentioning

confidence: 77%

“… 22 23 In contrast, there is limited information on the association between congenital malformation and an increased level of inhibin-A. 23 This study found an association between maternal serum inhibin-A in the second trimester with major fetal CHDs, but not with overall fetal cardiac defects. Women with high inhibin-A (≥2.5 MOM) had a 4.8-fold (95% CI 1.42–12.46) increased risk of major non-chromosomal fetal CHDs.…”

Section: Discussionmentioning

confidence: 77%

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study

et al. 2022

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Purpose We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. Materials and Methods This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. Results Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36–5.13] and major CHDs (aOR 7.30; 95% CI 3.18–15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42–12.46) was associated with non-chromosomal major CHDs. Conclusion Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

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“…These biomarkers were originally selected for prenatal screening due to their combined predictive value for fetal aneuploidies ( 26 , 45 ). In all cases, they have also proven to be associated with fetal growth restriction and/or birthweight ( 11 , 46 – 51 ). Pregnancy associated plasma protein (PAPPA) is a metalloproteinase that is produced primarily by the placenta in early pregnancy and promotes insulin growth factor (IGF) binding to its receptor ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight

Xun

Qin²,

Layden³

et al. 2022

Front. Reprod. Health

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Human chorionic gonadotropin (hCG) is a placental hormone measured in pregnancy to predict individual level risk of fetal aneuploidy and other complications; yet may be useful in understanding placental origins of child development more generally. hCG was associated with maternal body mass index (BMI) and with birthweight. The primary aim here was to evaluate hCG as a mediator of maternal BMI effects on birthweight by causal mediation analysis. Subjects were 356 women from 3 U.S. sites (2010–2013). The 4-way decomposition method using med4way (STATA) was applied to screen for 5 types of effects of first trimester maternal BMI on birthweight: the total effect, the direct effect, mediation by hCG, additive interaction of BMI and hCG, and mediation in the presence of an additive interaction. Effect modification by fetal sex was evaluated, and a sensitivity analysis was performed to evaluate the assumption of unmeasured confounding. Additional placental-fetal biomarkers [pregnancy associated plasma protein A (PAPPA), second trimester hCG, inhibin-A, estriol, alpha fetoprotein] were analyzed for comparison. For first trimester hCG, there was a 0.20 standard deviation increase in birthweight at the 75th vs. 25th percentile of maternal BMI (95% CI 0.04, 0.36). Once stratified, the direct effect association was null in women carrying females. In women carrying males, hCG did not mediate the relationship. In women carrying females, there was a mediated effect of maternal BMI on birthweight by hCG in the reverse direction (−0.06, 95% CI: −0.12, 0.01), and a mediated interaction in the positive direction (0.06, 95% CI 0.00, 0.13). In women carrying males, the maternal BMI effect on birthweight was reverse mediated by PAPPA (−0.09, 95% CI: −0.17, 0.00). Sex-specific mediation was mostly present in the first trimester. Second trimester AFP was a positive mediator of maternal BMI effects in male infants only (0.06, 95% CI: −0.01, 0.13). Effect estimates were robust to potential bias due to unmeasured confounders. These findings motivate research to consider first trimester placental biomarkers and sex-specific mechanisms when quantifying the effects of maternal adiposity on fetal growth.

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Are serum levels of inhibin A in second trimester predictors of adverse pregnancy outcome?

Cited by 11 publications

References 25 publications

Second trimester maternal serum biomarkers and the risk of cerebral palsy

Second trimester maternal serum biomarkers and the risk of cerebral palsy

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study

Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight

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