Prediction of small for gestational age neonates in twin pregnancies by first trimester maternal serum PAPP-A and free β-hCG

Introduction: Several studies suggested an association between first trimester biochemical markers (PAPP-A and β- HCG) and infants below 10th percentile. Our goal was to describe this relationship of biochemical markers with small-for- gestational-age fetuses in our population. Material and Methods: Retrospective analytic study of 2 035 pregnant women that underwent first-trimester screening in the period between March 2009 and September 2011. Small-for-gestational-age infants below 10th percentile were compared with control group (term newborn with birth weight above 10th percentile). Infants below 3rd percentile and control group were also compared. Multiple and logistic regression analysis were done with PAPP-A, β-HCG (multiples of the expected normal median) and demographic maternal characteristics (ethnicity, weight and smoker status). Results: This study demonstrated an independent contribution of PAPP-A, maternal weight and smoker status in predicting small-for-gestational-age infants. For PAPP-A, the odds ratio for small-for-gestational age below 10th and 3rd percentile was 2.41 and 3.41, respectively (p < 0.01). For β-HCG, odds ratio below 10th percentile was 1.70 (p = 0.03) and for birth weight below the 3rd percentile, the odds ratio was 3.22 (p < 0.01). Conclusions: Low levels of PAPP-A and β-HCG (values below 5th percentile of the study population) were associated with an increased risk of small-for-gestational-age infants in the pregnant population included in this study.

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The Relationship Between First-Trimester Aneuploidy Markers and Birth Weight

Gynecology Obstetrics and Reproductive Medicine ◽

10.21613/gorm.2021.1215 ◽

2021 ◽

pp. 1-6

Author(s):

Cenk Soysal ◽

İsmail Biyik ◽

Özlem Erten ◽

Onur Ince ◽

Hatice Sari ◽

...

Keyword(s):

Plasma Protein ◽

Gestational Age ◽

Small For Gestational Age ◽

Protein A ◽

First Trimester ◽

Nuchal Translucency ◽

Maternal Serum ◽

Large For Gestational Age ◽

Aneuploidy Screening ◽

Beta Human Chorionic Gonadotropin

OBJECTIVE: We aimed to determine the relationship between the first-trimester aneuploidy screeningma and the predicted weight at birth: Small for gestational age and large for gestational age. STUDY DESIGN: 594 low-risk pregnant women with a singleton pregnancy, who underwent first-trimester aneuploidy screening by measuring nuchal translucency, maternal serum free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein-A were included in the study. Those weighing above the 3rd percentile and below the 10th percentile were defined as small for gestational age, and those over the 90th percentile were defined as large for gestational age. RESULTS: A total of 594 pregnant women were enrolled. The mean maternal age of the studied group was 28.8±5.5 years. Low maternal serum pregnancy-associated plasma protein-A levels and decreased nuchal translucency measurements were associated with the small for gestational age newborn (p<0.001 and p=0.001, respectively). There is a significant correlation with large for gestational age for newborns only with an increase in maternal serum pregnancy-associated plasma protein-A levels (p=0.001). beta-human chorionic gonadotropin levels were not associated with the birth weight (p=0.735). CONCLUSION: Maternal serum pregnancy-associated plasma protein-A levels, one of the markers in first-trimester aneuploidy screening, can be used in the prediction of small for gestational age and large for gestational age However, due to its low correlation, it is not a suitable screening test for clinical practice.

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High Maternal Serum Estradiol Environment in the First Trimester Is Associated With the Increased Risk of Small-for-Gestational-Age Birth

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-3362 ◽

2014 ◽

Vol 99 (6) ◽

pp. 2217-2224 ◽

Cited By ~ 59

Author(s):

Xiao-Ling Hu ◽

Chun Feng ◽

Xian-Hua Lin ◽

Zi-Xing Zhong ◽

Yi-Min Zhu ◽

...

Keyword(s):

Birth Weight ◽

Gestational Age ◽

Small For Gestational Age ◽

First Trimester ◽

Maternal Serum ◽

Serum Estradiol ◽

Ideal Model ◽

Fresh Embryo Transfer ◽

Increased Risk ◽

The Mean

Context: There are increasing concerns that a disrupted endocrine environment may disturb the growth of the fetus. Assisted reproductive technology (ART) situates gamete/embryo in a supraphysiological estradiol (E2) environment and, thus, provides an ideal model to investigate this problem. Objective: Our objective was to investigate whether the maternal high-E2 environment in the first trimester increases the risks of low birth weight (LBW) and small-for-gestational-age (SGA) birth. Methods: In total, 8869 singletons born after fresh embryo transfer (ET) (n = 2610), frozen ET (n = 1039), and natural conception (NC) (n = 5220) and their mothers were included. Birth weight, LBW, SGA, and maternal serum E2 levels were investigated. Results: The mean serum E2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were significantly higher than those of the women undergoing frozen ET and the women with NC (P < .01). Serum E2 levels of women undergoing fresh ET at 4 and 8 weeks of gestation were positively correlated to those on the day of human chorionic gonadotropin (hCG) administration (r = 0.5 and r = 0.4, respectively; P < 0.01). The birth weight after fresh ET was significantly lower than that after frozen ET and NC (P < 0.01), with increased incidence of LBW and SGA (P < .05). Furthermore, in the fresh ET group, singletons of mothers with high E2 levels (≥10460 pmol/L on the day of hCG administration) had higher risks of LBW (P < .01) and SGA (P < .01) than those with low E2 levels, and maternal serum E2 level on the day of hCG administration negatively correlated with the birth weight (P < .01). Conclusions: The maternal high-E2 environment in the first trimester is correlated with increased risks of LBW and SGA. Evaluation of serum E2 before ET should be adopted to reduce the possibility of high E2 exposure to gamete/embryo.

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High Maternal Serum Estradiol in First Trimester of Multiple Pregnancy Contributes to Small for Gestational Age via DNMT1-Mediated CDKN1C Upregulation

Reproductive Sciences ◽

10.1007/s43032-021-00735-8 ◽

2021 ◽

Author(s):

Xiao-Ling Hu ◽

Shuai Shi ◽

Ning-Ning Hou ◽

Ye Meng ◽

Miao Li ◽

...

Keyword(s):

Birth Weight ◽

Cord Blood ◽

Gestational Age ◽

Small For Gestational Age ◽

Multiple Pregnancy ◽

First Trimester ◽

Maternal Serum ◽

Serum Estradiol ◽

Multiple Pregnancies ◽

Embryo Tissue

AbstractHigh maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

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Association Between Twin Discordance at 6–9 Weeks' of Gestation and Birthweight Complications

Twin Research and Human Genetics ◽

10.1375/twin.13.4.389 ◽

2010 ◽

Vol 13 (4) ◽

pp. 389-392 ◽

Cited By ~ 4

Author(s):

Kirsten Palmer ◽

Pavitra Delpachitra ◽

Joseph Onwude ◽

Luk Rombauts ◽

Simon Meagher ◽

...

Keyword(s):

Clinical Significance ◽

Gestational Age ◽

Small For Gestational Age ◽

First Trimester ◽

In Vitro Fertilisation ◽

Crown Rump Length ◽

Increased Risk ◽

Twin Pregnancies

AbstractTwins achieved through in-vitro fertilisation often undergo a viability ultrasound at 6–9 weeks of gestation. The presence of inter-twin crown-rump length discordance at this stage is not an uncommon finding; however the clinical significance of this is unknown. We analyzed 218 dichorionic twin pregnancies, producing two live fetuses > 24 weeks gestation, to determine whether inter-twin discordance (≥ 85th centile) in the mid-first trimester was associated with birthweight discordance (> 20%), or small for gestational age (< 10th centile). The incidence of birthweight discordance and small for gestational age infants were determined, with no increased risk found for the discordant population. This may provide some reassurance to treating clinicians.

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First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.12537 ◽

2013 ◽

Vol 43 (1) ◽

pp. 34-40 ◽

Cited By ~ 39

Author(s):

F. Crovetto ◽

F. Crispi ◽

E. Scazzocchio ◽

I. Mercade ◽

E. Meler ◽

...

Keyword(s):

Blood Pressure ◽

Gestational Age ◽

Small For Gestational Age ◽

Uterine Artery ◽

First Trimester ◽

Serum Biochemistry ◽

Maternal Serum ◽

First Trimester Screening ◽

Uterine Artery Doppler ◽

Trimester Screening

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First Trimester Maternal Cortisol Signatures in Small-for-gestational Age

10.21203/rs.3.rs-589673/v1 ◽

2021 ◽

Author(s):

Chaelin Lee ◽

Seung Mi Lee ◽

Dong Jun Byun ◽

So Yeon Kim ◽

Hugh I. Kim ◽

...

Keyword(s):

Pregnant Women ◽

Gestational Age ◽

Small For Gestational Age ◽

Serum Levels ◽

First Trimester ◽

Maternal Serum ◽

Serum Samples ◽

Cortisol Metabolism ◽

Cortisol Ratio ◽

Pituitary Adrenal Axis

Abstract Background: Abnormal maternal hypothalamus-pituitary-adrenal axis is associated with fetal growth, and we hypothesized that the alteration in metabolic signatures of cortisol might be detectable during early pregnancy. The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational age (SGA) neonates.Methods: This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10~14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry.Results: Increased maternal serum levels of tetrahydrocortisol (THF, 11.82 ± 8.16 ng/mL vs. 7.51 ± 2.90 ng/mL, P < 0.005) and decreased 21-deoxycortisol (21-deoxyF, 2.98 ± 1.36 ng/mL vs. 4.33 ± 2.06 ng/mL, P < 0.0001) were observed in pregnant women carrying SGA fetus. In conjunction with individual steroid levels, metabolic ratios corresponding to the activity of related enzymes were calculated. In addition to increased THF/cortisol ratio (P < 0.006), the SGA group showed a significant increase in the two metabolic ratios including cortisol/11-deoxycortisol (F/11-deoxyF; P < 0.03) and cortisol/21-deoxycortisol (F/21-deoxyF; P < 0.0003) indicating cortisol biosynthesis. The ROC curve generated in combination with three variables of 21-deoxyF concentration and two metabolic ratios of F/21-deoxyF and THF/F resulted in AUC = 0.824 (95% confidence interval, 0.713 ~ 0.918). Conclusions: A significant decrease in maternal serum levels of 21-deoxyF and an increase in two metabolic ratios of F/21-deoxyF and THF/F, indicating cortisol biosynthetic rate, represent a reliable biomarker for the prediction of SGA in the first trimester.

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