Markers Of Placental Function Research Articles

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

8331 Melatonin is associated with higher placental weight and higher birth weight

Abstract Disclosure: U. Kampmann: Grant Recipient; Self; Novo Nordisk, Ulla Kampmann. Speaker; Self; Merck, Novo Nordisk. E.S. Lauritzen: None. S. Knorr: None. M. Bjerre: None. L.J. Goodyear: None. R. Middelbeek: None. J. Kusuyama: None. J. Fuglsang: None. P. Ovesen: Grant Recipient; Self; Novo Nordisk. M. Møller: None. Background and aim: Melatonin is both a neuroendocrine hormone which regulates circadian rhythm and an antioxidant. Melatonin is primarily produced in the pineal gland but also in the placenta and the role of melatonin in pregnancy is emerging. We examined melatonin levels during pregnancy and performed correlations with placental weight, birth weight and birth weight Z-score as markers of placental function. Material and methods: Blood samples were obtained in each trimester of pregnancy from a cohort of 400 pregnant women, followed at a Danish University Hospital. Data on pre-gestational BMI, smoking status, placental weight, birth weight and Z-score were collected. Melatonin, and biomarkers of oxidative stress: SOD3, CD 163 and CRP were measured on blood samples collected in the morning. Correlations were calculated using mixed models. Results: We included 372 healthy, singleton pregnancies. Melatonin levels increased significantly throughout pregnancy from 17.0 pg/mL (95% CI: 14.1 - 19.9) and 18.8 pg/mL (95% CI: 15.8 - 21.8) in the 1st and 2nd trimester, respectively, to 45.9 pg/mL (95% CI: 40.8 - 51.0) in the 3rd trimester. There was a significant positive correlation between the antioxidant enzyme SOD3 and melatonin throughout pregnancy with a coefficient of 0.15 (95% CI: 0.13 - 0.17) and there was a significant positive association between placental weight and melatonin (coefficient: 0.014 (95% CI: 0.000 - 0.028)) and Z-score and melatonin levels (coefficient: 1.95 (95% CI: 0.13 - 3.79)). This was however not significant when adjusting for smoking and pre-pregnancy BMI. Conclusion: The current study is to date, the largest study that have performed longitudinal measures of melatonin throughout pregnancy. Melatonin levels increase significantly during pregnancy and indicate that placenta is a major source of melatonin, that plays a protective role against oxidative stress in pregnancy. Presentation: 6/1/2024

8331 Melatonin is associated with higher placental weight and higher birth weight

Abstract Disclosure: U. Kampmann: Grant Recipient; Self; Novo Nordisk, Ulla Kampmann. Speaker; Self; Merck, Novo Nordisk. E.S. Lauritzen: None. S. Knorr: None. M. Bjerre: None. L.J. Goodyear: None. R. Middelbeek: None. J. Kusuyama: None. J. Fuglsang: None. P. Ovesen: Grant Recipient; Self; Novo Nordisk. M. Møller: None. Background and aim: Melatonin is both a neuroendocrine hormone which regulates circadian rhythm and an antioxidant. Melatonin is primarily produced in the pineal gland but also in the placenta and the role of melatonin in pregnancy is emerging. We examined melatonin levels during pregnancy and performed correlations with placental weight, birth weight and birth weight Z-score as markers of placental function. Material and methods: Blood samples were obtained in each trimester of pregnancy from a cohort of 400 pregnant women, followed at a Danish University Hospital. Data on pre-gestational BMI, smoking status, placental weight, birth weight and Z-score were collected. Melatonin, and biomarkers of oxidative stress: SOD3, CD 163 and CRP were measured on blood samples collected in the morning. Correlations were calculated using mixed models. Results: We included 372 healthy, singleton pregnancies. Melatonin levels increased significantly throughout pregnancy from 17.0 pg/mL (95% CI: 14.1 - 19.9) and 18.8 pg/mL (95% CI: 15.8 - 21.8) in the 1st and 2nd trimester, respectively, to 45.9 pg/mL (95% CI: 40.8 - 51.0) in the 3rd trimester. There was a significant positive correlation between the antioxidant enzyme SOD3 and melatonin throughout pregnancy with a coefficient of 0.15 (95% CI: 0.13 - 0.17) and there was a significant positive association between placental weight and melatonin (coefficient: 0.014 (95% CI: 0.000 - 0.028)) and Z-score and melatonin levels (coefficient: 1.95 (95% CI: 0.13 - 3.79)). This was however not significant when adjusting for smoking and pre-pregnancy BMI. Conclusion: The current study is to date, the largest study that have performed longitudinal measures of melatonin throughout pregnancy. Melatonin levels increase significantly during pregnancy and indicate that placenta is a major source of melatonin, that plays a protective role against oxidative stress in pregnancy. Presentation: 6/1/2024

Maternal thyroid function and biochemical markers of placental function in early pregnancy

Maternal thyroid function and biochemical markers of placental function in early pregnancy

Maternal cardiovascular function in midgestation is related to placental angiogenesis.

To investigate whether angiogenic markers of placental function are associated with maternal cardiac function and hemodynamic responses at 19-23 weeks' gestation, controlling for maternal risk factors and pregnancy complications. This was a prospective study of women with singleton pregnancy attending King's College Hospital, London, UK, for a routine hospital visit at 19-23 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure (MAP), maternal heart rate, serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We also performed maternal echocardiography to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function. Our cohort included 4006 women. Lower PlGF values were significantly associated with higher MAP (P < 0.0001), lower maternal heart rate (P < 0.0001), lower mitral valve s' mean velocity (P = 0.027) and higher left atrial area (P = 0.022) after adjustment for maternal characteristics and pregnancy complications. sFlt-1 was associated positively with relative wall thickness (P = 0.012), whereas sFlt-1/PlGF ratio was associated negatively with mitral valve A (P = 0.006) and positively with left atrial area (P = 0.015) and MAP (P = 0.004). The magnitude of these associations was similar in the subgroup of women without any risk factors based on their obstetric and medical history. A continuous association of moderate strength between angiogenic factors and subclinical maternal cardiac function alterations is present in midgestation, independently of pre-existing maternal risk factors and pregnancy complications. Impaired placental function appears to be related to mild systolic and diastolic dysfunction and cardiac remodeling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of COVID-19 and Vaccination During Pregnancy on Placenta-Mediated Complications (COVIGRO Study)

ObjectivesCOVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function. MethodsWe performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021). At each trimester of pregnancy, the assessment included a questionnaire on COVID-19 and vaccination status; serological tests for COVID-19 (for asymptomatic infection); measurement of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in maternal blood; measurement of mean uterine artery pulsatility index (UtA-PI); and pregnancy outcomes (PTB, PE, birth weight below the fifth and the tenth percentile). ResultsAmong 788 patients with complete data, we observed 101 (13%) cases of symptomatic infection and 74 (9%) cases of asymptomatic infection with SARS-CoV-2. Most cases (73%) of infection were among women with previous vaccination or COVID-19 infection before pregnancy. COVID-19 infection was not associated with adverse pregnancy outcomes, abnormal fetal growth, sFlt-1/PlGF ratio, or mean UtA-PI. Vaccination during pregnancy did not influence these outcomes either. We observed no case of severe COVID-19 infection requiring respiratory support. ConclusionMild symptomatic or asymptomatic COVID-19 during pregnancy did not influence the risk of adverse pregnancy outcomes and the markers of placental function in predominantly vaccinated women. Fetal growth monitoring is unlikely to be mandatory in women with mild symptoms of COVID-19.

EP18.35: The FIGO nutritional score in the first trimester of pregnancy and its influence on early placental function markers and pregnancy outcomes

EP18.35: The FIGO nutritional score in the first trimester of pregnancy and its influence on early placental function markers and pregnancy outcomes

Serum Human Placental Lactogen Assays in Ultrasound Evaluated Pregnancy-Induced Hypertension: A Marker of Placental Function in Pregnancy.

Human placental lactogen (HPL) is a pregnancy-related hormone produced by the placenta. The overall functions of serum HPL impacts the developing fetus and placenta. The objective of this study was to determine the relationship between maternal serum concentration of HPL and sonographic fetal growth parameters in pregnancy induced hypertension as a marker of placental function. This prospective cross-sectional study was conducted over a 9-month period in the University of Calabar Teaching Hospital, Calabar, Nigeria that involved 100 women with pregnancy induced hypertension. An obstetric ultrasound scan was done on all the subjects and their blood was collected for HPL evaluation using Enzyme-linked Immunosorbent Assay (ELISA). SPSS version 20 was used to analyze the data. Maternal serum HPL had a significant positive correlation with PLA (P=0.000), estimated gestational age (P=0.000), estimated fetal weight (P=0.000) and amniotic fluid index AFI (P=0.000) and a significant negative correlation with proteinuria (P=0.047), fetal heart rate (P=0.032) and HC/AC (P=0.000). It is concluded that maternal serum HPL concentration increases as pregnancy advances and causes a significant increase in placental thickness, fetal weight and amniotic fluid volume, however, its reduction is significantly associated with the onset of pre-eclampsia, fetal distress and asymmetrical intra-uterine growth restriction. Thus, the evaluation of maternal serum HPL concentration is a reliable marker of placental function in the second half of pregnancy.

Markers of placental function correlate with prevalence and quantity of nucleated fetal cells in maternal circulation in normotensive term pregnancies.

Transplacental fetal cell transfer results in the engraftment of fetal-origin cells in the pregnant woman's body, a phenomenon termed fetal microchimerism. Increased fetal microchimerism measured decades postpartum is implicated in maternal inflammatory disease. Understanding which factors cause increased fetal microchimerism is therefore important. During pregnancy, circulating fetal microchimerism and placental dysfunction increase with increasing gestational age, particularly towards term. Placental dysfunction is reflected by changes in circulating placenta-associated markers, specifically placental growth factor (PlGF), decreased by several 100 pg/mL, soluble fms-like tyrosine kinase-1 (sFlt-1), increased by several 1000 pg/mL, and the sFlt-1/PlGF ratio, increased by several 10 (pg/mL)/(pg/mL). We investigated whether such alterations in placenta-associated markers correlate with an increase in circulating fetal-origin cells. We included 118 normotensive, clinically uncomplicated pregnancies (gestational age 37+1 up to 42+2 weeks' gestation) pre-delivery. PlGF and sFlt-1 (pg/mL) were measured by Elecsys® Immunoassays. We extracted DNA from maternal and fetal samples and genotyped four human leukocyte antigen loci and 17 other autosomal loci. Paternally inherited, unique fetal alleles served as polymerase chain reaction (PCR) targets for detecting fetal-origin cells in maternal buffy coat. Fetal-origin cell prevalence was assessed by logistic regression, and quantity by negative binomial regression. Statistical exposures included gestational age (weeks), PlGF (100 pg/mL), sFlt-1 (1000 pg/mL) and the sFlt-1/PlGF ratio (10 (pg/mL)/(pg/mL)). Regression models were adjusted for clinical confounders and PCR-related competing exposures. Gestational age was positively correlated with fetal-origin cell quantity (DRR = 2.2, P = 0.003) and PlGF was negatively correlated with fetal-origin cell prevalence (odds ratio [OR]100 = 0.6, P = 0.003) and quantity (DRR100 = 0.7, P = 0.001). The sFlt-1 and the sFlt-1/PlGF ratios were positively correlated with fetal-origin cell prevalence (OR1000 = 1.3, P = 0.014 and OR10 = 1.2, P = 0.038, respectively), but not quantity (DRR1000 = 1.1, P = 0.600; DRR10 = 1.1, P = 0.112, respectively). Our results suggest that placental dysfunction as evidenced by placenta-associated marker changes, may increase fetal cell transfer. The magnitudes of change tested were based on ranges in PlGF, sFlt-1 and the sFlt-1/PlGF ratio previously demonstrated in pregnancies near and post-term, lending clinical significance to our findings. Our results were statistically significant after adjusting for confounders including gestational age, supporting our novel hypothesis that underlying placental dysfunction potentially is a driver of increased fetal microchimerism.

Prospective multicentre Italian pregnancy cohort study (SIMPLE) on the associations of maternal first trimester SIMPLE nutritional score with early placental function markers and pregnancy outcomes

IntroductionCurrently, the adherence to nutritional guidelines is low, with alarming rates of obesity worldwide and micronutrient deficiencies documented even in industrialised countries. As a consequence, nutritional screening and counselling represent...

Male Embryos Produced in vitro Deviate From Their in vivo Counterparts in Placental Gene Expression on Day 32 of Pregnancy

This study compared the gene expression of extraembryonic membranes (EEM) from in vitro produced (IVP) and in vivo (AI) derived pregnancies. A piece of conceptus (day 18) or chorioallantois (day 32) was used for DNA and RNA isolation and sex determination. Male and female ratios were analyzed by Chi-square. A total of three samples per sex and group (AI and IVP, days 18 and 32) were used for transcriptome analysis. Differentially expressed genes (DEGs) were determined using edgeR-robust. A false discovery rate (FDR) &amp;lt;0.05 was used for statistical significance. Sex ratio was similar on day 18 for AI and IVP groups. On day 32, the IVP group had a greater number of females than males (75 vs. 25%, P = 0.004). When comparing AI and IVP males vs. females, in both groups, genes upregulated in females on day 18 were related to placental function such as PAGs and TKDPs. On males on day 18, IFNT-related genes were upregulated. Comparing the techniques within sex, on day 18 female conceptuses, 50 genes were upregulated in IVP, and 21 in AI. IGF2, which is involved in placenta development, and APOA2, APOB, and APOE, involved in lipid metabolism, were upregulated in IVP conceptuses. On day 18, males had 15 upregulated genes in AI and 7 in IVP. On day 32, females had 21 upregulated genes in AI and 53 in IVP. Genes involved in lipid synthesis and metabolism were increased in the IVP group. Males on day 32 presented 899 DEGs, 564 upregulated in AI and 335 in IVP. Embryos from IVP had decreased expression of genes related to lipid and carbohydrate metabolism. Interestingly, pregnancy-associated glycoproteins (PAG) 7, 9, 10, and 19, were downregulated in IVP male. In conclusion, IVP-derived male embryos were more susceptible to alterations in gene expression and these effects extend to the peri-implantation period including genes associated with placental development and markers of placental function.

New insights into human functional ultrasound imaging.

Ultrasound imaging is a vital tool for exploring in vivo the placental function which is essential to understand pathological phenomena such as preeclampsia or intrauterine growth restriction. As technology advances including ready availability of three-dimensional (3D) probes and novel software, new markers of placental function become possible. The objective of this review was to provide an overview of the new ultrasound markers of placental function with a focus on the potential clinical application of three-dimensional power Doppler (3DPD). A broad-free text literature search was undertaken based on human placental studies and sixty full-text studies were included in this review. Three-dimensional power Doppler is a promising technique to predict preeclampsia in the first trimester. However, the influence of external factors such as body mass index, parameter standardisation and machine settings still need to be addressed. Contrast-enhanced ultrasound is currently reserved for research, because the required injected contrast mediums are not currently approved for use in pregnancy, although the safety data is reassuring.

Maternal Short-Term Exposure to No2 During Pregnancy and its Relationship with Doppler Markers of Placental Function

Maternal Short-Term Exposure to No2 During Pregnancy and its Relationship with Doppler Markers of Placental Function

Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications.

ContextAntenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications.ObjectiveWe aimed to assess whether kisspeptin levels are altered in women with antenatal complications.MethodsWomen with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed.ResultsThird-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P < 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; P = 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (P = 0.014) and lower in those with GDM (P = 0.020), but not significantly on multivariable analysis.ConclusionWe delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

The impact of low-dose aspirin on markers of inflammation and placental function: an ancillary study of the ASPIRIN trial

Objective To determine the impact of low-dose aspirin (81 mg) on markers of maternal inflammation and placental function. Setting Rural Southern India Population Nulliparous women with a singleton pregnancy dated by ultrasound who were enrolled in the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) Trial. Methods We performed a case-control study to elucidate the impact of low dose aspirin (LDA) on markers of placental function and maternal inflammation among women who delivered prematurely compared to term controls in women enrolled in the ASPIRIN trial. Women were prospectively enrolled in an ancillary observational trial wherein maternal serum was collected and measured between 10 to 13 weeks and 17 to 21 weeks of gestation after initiation of aspirin or an identical placebo. Results From 2016-18 with a total of 666 n women enrolled in this ancillary trial of whom 269 were selected for analyte analysis. Women who received LDA had lower levels of Alpha Feto-Protein (AFP) at 10 to 13 weeks than women who received placebo (Placebo) (LDA 18.3 ng/mL vs 21.4 ng/mL -P 0.001). AFP was similar between the two groups at 17 to 21 weeks. No other differences were seen in C-Reactive protein or Anti-Mullerian Hormone. Conclusion Low-dose aspirin administration lowers AFP early in pregnancy.

Placental chemical elements concentration in small fetuses and its relationship with Doppler markers of placental function

IntroductionIn this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. MethodsProspective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. ResultsSGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. DiscussionLower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.

Associations between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus.

Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body-mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk (p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations (p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM (p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association.

Pregnancy and postpartum levels of circulating maternal sHLA-G in preeclampsia

Preeclampsia is a leading cause of maternal and offspring mortality and morbidity, and predicts increased future cardiovascular disease risk. Placental dysfunction and immune system dysregulation are likely key pathophysiological factors. Soluble human leukocyte antigen G (sHLA-G) may dampen the specific immune response towards placental trophoblasts. Previous studies have shown low sHLA-G levels in preeclampsia, but postpartum, levels are unknown. Furthermore, the relationship between sHLA-G and sFlt-1 and PlGF, placental function markers, is unknown. We hypothesized that low maternal sHLA-G during pregnancy would be associated with placental dysfunction, including preeclampsia, gestational hypertension, and dysregulated sFlt-1 and PlGF, and that sHLA-G would remain decreased following preeclampsia.We included 316 pregnant women: 58 with early-onset preeclampsia (<34 weeks’ gestation), 81 with late-onset preeclampsia (≥34 weeks’ gestation), 25 with gestational hypertension, and 152 normotensive controls. Postpartum (1 or 3 years), we included 321 women: 29 with early-onset preeclampsia, 98 with late-onset preeclampsia, 57 with gestational hypertension, and 137 who were normotensive during their index pregnancies.In pregnancy, plasma sHLA-G was significantly lower both in the early- and late-onset preeclampsia groups compared to controls. In women with preeclampsia or gestational hypertension, sHLA-G was inversely correlated with serum sFlt-1. Postpartum, plasma sHLA-G levels were significantly higher in women who had had early-onset preeclampsia compared to controls.Our results support that sHLA-G may be important for placental function. Unexpectedly, sHLA-G was elevated up to 3 years after early-onset preeclampsia, suggesting an excessively activated immune system following this severe preeclampsia form, potentially contributing to future cardiovascular disease risk.

Associations between First Trimester Maternal Nutritional Score, Early Markers of Placental Function, and Pregnancy Outcome.

This study investigated the associations between maternal adherence to a healthy diet, first trimester placental markers, and pregnancy outcome. Singleton spontaneous pregnancies were enrolled at 11+0–13+6 gestational weeks in a prospective cohort study. A nutritional score (0–10) measuring the adherence to a healthy diet was calculated. A transabdominal ultrasound scan for placental marker assessment was performed (uterine artery (UtA) doppler, placental volume). Biochemical placental markers were recorded (Pregnancy Associated Plasma Protein A (PAPP-A), free β- Human Chorionic Gonadotropin (HCG)). Birth outcomes were obtained from medical records. Associations between the maternal nutritional score, first trimester placental markers, and pregnancy outcome were investigated by using multi-adjusted general linear models. In total, 112 pregnancies were enrolled with a median nutritional score of 7 (range 3–10). Median gestational age at birth was 277 days (range 203–296). The nutritional score was positively associated with PAPP-A concentrations, whereas a negative association was detected with the UtA mean pulsatility index and placental volume. A positive association was detected between nutritional score and gestational age at birth. This study demonstrates that a first trimester nutritional score as a measure of adherence to a healthy diet is significantly associated with early biochemical and ultrasound markers of placental development, with further association with gestational age at birth.

First-trimester placental function in levothyroxine-using pregnant women: a case-control study

We aimed to compare the pregnancy-associated plasma protein-A (PAPP-A) and the uterine artery pulsatility index (UtA PI) levels of euthyroid pregnant women using levothyroxine vs. a control group of uncomplicated pregnancies and to evaluate the effects of different levothyroxine dosages on pregnancy outcomes. We retrospectively evaluated 206 levothyroxine-using pregnant women by looking at their basic placental function markers and obstetric outcomes. A sample of 449 women whose pregnancies concluded with uncomplicated term deliveries composed of our control group. To examine the relationship between the levothyroxine dosages and the frequency of pregnancy complications, levothyroxine users were divided into different groups according to the 75, 100, and 150 mcg cutoffs. The median PAPP-A MoM levels of levothyroxine users were significantly lower at 0.94 vs. 1.11 (p < .001) and the median mean UtA PI was significantly higher than the control group at 2.08 vs. 1.74 (p < .0001). The median birth weight was significantly lower for the levothyroxine users’ group at 3292 g vs. 3427 g (p < .0001). Using 75, 100, and 150 mcg dose cutoffs, PAPP-A MoM, mean UtA PI and obstetric complication frequencies were not significantly different among levothyroxine users. Significant changes in placental function markers have been observed in euthyroid levothyroxine-using pregnant women during the first trimester. However, the frequency of obstetric complications does not appear to be dose dependent.