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

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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Marcadores Bioquímicos do Primeiro Trimestre e Recém-Nascidos Leves para Idade Gestacional

Acta Médica Portuguesa ◽

10.20344/amp.3985 ◽

2014 ◽

Vol 27 (2) ◽

pp. 191

Author(s):

Cláudia Andrade ◽

Joana Santos ◽

Ana Rita Pinto ◽

Pedro Manso ◽

Susana Pereira

Keyword(s):

Birth Weight ◽

Gestational Age ◽

Small For Gestational Age ◽

Odds Ratio ◽

Biochemical Markers ◽

First Trimester ◽

Control Group ◽

Maternal Weight ◽

Increased Risk ◽

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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Perinatal Outcomes of Small for Gestational Age in Twin Pregnancies: Twin vs. Singleton Charts

Journal of Clinical Medicine ◽

10.3390/jcm10040643 ◽

2021 ◽

Vol 10 (4) ◽

pp. 643

Author(s):

Veronica Giorgione ◽

Corey Briffa ◽

Carolina Di Fabrizio ◽

Rohan Bhate ◽

Asma Khalil

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Gestational Age ◽

Small For Gestational Age ◽

Perinatal Death ◽

Perinatal Outcomes ◽

Adverse Outcomes ◽

Chi Square ◽

Increased Risk ◽

Twin Pregnancies

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally.

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High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

American Journal of Perinatology ◽

10.1055/s-0039-1694005 ◽

2019 ◽

Vol 37 (01) ◽

pp. 008-013 ◽

Cited By ~ 4

Author(s):

Lydia L. Shook ◽

Mark A. Clapp ◽

Penelope S. Roberts ◽

Sarah N. Bernstein ◽

Ilona T. Goldfarb

Keyword(s):

Preterm Birth ◽

Gestational Age ◽

Small For Gestational Age ◽

First Trimester ◽

Hypertensive Disorders Of Pregnancy ◽

Aneuploidy Screening ◽

Hypertensive Disorders ◽

Increased Risk ◽

Adverse Pregnancy ◽

Fetal Fraction

Abstract Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.

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

Perinatal Journal ◽

10.2399/prn.14.0223009 ◽

2014 ◽

Vol 22 (3) ◽

pp. 152-155

Author(s):

Dilek Beker Şanlı ◽

Kazım Kartkaya ◽

Fezan Şahin Mutlu

Keyword(s):

Gestational Age ◽

Small For Gestational Age ◽

First Trimester ◽

Maternal Serum ◽

Β Hcg ◽

Twin Pregnancies

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Dengue during pregnancy and live birth outcomes: a cohort of linked data from Brazil

BMJ Open ◽

10.1136/bmjopen-2018-023529 ◽

2019 ◽

Vol 9 (7) ◽

pp. e023529 ◽

Cited By ~ 2

Author(s):

Enny S Paixão ◽

Oona M Campbell ◽

Maria Gloria Teixeira ◽

Maria CN Costa ◽

Katie Harron ◽

...

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Low Birth Weight ◽

Birth Outcomes ◽

Live Birth ◽

Gestational Age ◽

Small For Gestational Age ◽

Severe Dengue ◽

Maternal Risk ◽

Increased Risk

ObjectivesDengue is the most common viral mosquito-borne disease, and women of reproductive age who live in or travel to endemic areas are at risk. Little is known about the effects of dengue during pregnancy on birth outcomes. The objective of this study is to examine the effect of maternal dengue severity on live birth outcomes.Design and settingWe conducted a population-based cohort study using routinely collected Brazilian data from 2006 to 2012.ParticipatingWe linked birth registration records and dengue registration records to identify women with and without dengue during pregnancy. Using multinomial logistic regression and Firth method, we estimated risk and ORs for preterm birth (<37 weeks’ gestation), low birth weight (<2500 g) and small for gestational age (<10thcentile). We also investigated the effect of time between the onset of the disease and each outcome.ResultsWe included 16 738 000 live births. Dengue haemorrhagic fever was associated with preterm birth (OR=2.4; 95% CI 1.3 to 4.4) and low birth weight (OR=2.1; 95% CI 1.1 to 4.0), but there was no evidence of effect for small for gestational age (OR=2.1; 95% CI 0.4 to 12.2). The magnitude of the effects was higher in the acute disease period.ConclusionThis study showed an increased risk of adverse birth outcomes in women with severe dengue during pregnancy. Medical intervention to mitigate maternal risk during severe acute dengue episodes may improve outcomes for infants born to exposed mothers.

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The Role of Early Pregnancy Maternal Selenium Levels on the Risk for Small-for-Gestational Age Newborns

Nutrients ◽

10.3390/nu11102298 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2298 ◽

Cited By ~ 9

Author(s):

Małgorzata Lewandowska ◽

Stefan Sajdak ◽

Jan Lubiński

Keyword(s):

Birth Weight ◽

Early Pregnancy ◽

Gestational Age ◽

Small For Gestational Age ◽

Inductively Coupled Plasma ◽

Maternal Serum ◽

Risk Marker ◽

Serum Selenium ◽

Odds Ratios ◽

Oxidative Balance

It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10–14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) (n = 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10–90th percentile) (n = 192). We measured the maternal microelement concentrations in the serum from the 10–14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L; p = 0.020). Women in the lowest Q1 quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q2 or Q4); the odds ratio of SGA was OR = 3.02 (p = 0.019) for Q1 vs. Q2 quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups.

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