Ultrasonographic placental parameters at 11-13+6 weeks' gestation in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVE: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11-13 + 6 weeks' gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). MATERIALS AND METHODS: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11-13 + 6 weeks' gestation. Logistic regression analysis was performed to determine the significant predictors of complications. RESULTS: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492-0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510-0.779; p = 0.026), respectively. CONCLUSION: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

Prediction of labour outcomes using prelabour computerised cardiotocogram and maternal and fetal Doppler indices: A prospective cohort study.

OBJECTIVES: To investigate the association and the potential value of prelabour fetal heart rate short-term variability (STV) determined by computerised cardiotocography (cCTG) and maternal and fetal Doppler in predicting labour outcomes. DESIGN: Prospective cohort study. SETTING: The Prince of Wales Hospital, a tertiary maternity unit, in Hong Kong SAR. POPULATION: Women with a term singleton pregnancy in latent phase of labour or before labour induction were recruited during May 2019-November 2021. METHODS: Prelabour ultrasonographic assessment of fetal growth, Doppler velocimetry and prelabour cCTG monitoring including Dawes-Redman CTG analysis were registered shortly before induction of labour or during the latent phase of spontaneous labour. MAIN OUTCOME MEASURES: Umbilical cord arterial pH, emergency delivery due to pathological CTG during labour and neonatal intensive care unit (NICU)/special care baby unit (SCBU) admission. RESULTS: Of the 470 pregnant women invited to participate in the study, 440 women provided informed consent and a total of 400 participants were included for further analysis. Thirty-four (8.5%) participants underwent emergency delivery for pathological CTG during labour. A total of 6 (1.50%) and 148 (37.00%) newborns required NICU and SCBU admission, respectively. Middle cerebral artery pulsatility index (MCA-PI) and MCA-PI z-score were significantly lower in pregnancies that required emergency delivery for pathological CTG during labour compared with those that did not (1.23 [1.07-1.40] versus 1.40 [1.22-1.64], p = 0.002; and 0.55 ± 1.07 vs. 0.12 ± 1.06), p = 0.049]. This study demonstrated a weakly positive correlation between umbilical cord arterial pH and prelabour log10 STV (r = 0.107, p = 0.035) and the regression analyses revealed that the contributing factors for umbilical cord arterial pH were smoking (p = 0.006) and prelabour log10 STV (p = 0.025). CONCLUSIONS: In pregnant women admitted in latent phase of labour or for induction of labour at term, prelabour cCTG STV had a weakly positive association with umbilical cord arterial pH but was not predictive of emergency delivery due to pathological CTG during labour.

First Trimester Screening for Gestational Diabetes Mellitus with Maternal Factors and Biomarkers.

INTRODUCTION: This study aimed to identify risk factors among maternal characteristics, obstetric history, and first trimester preeclampsia-specific biomarkers that were associated with subsequent development of gestational diabetes mellitus (GDM) and evaluate the performance of the prediction models. METHODS: This study was a secondary analysis of a prospective cohort study. The performance of the prediction models was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 837 (8.9%) cases of GDM and 8,535 (91.1%) unaffected cases were included. The AUROC of the prediction model combining maternal characteristics and obstetric history (0.735) was better than that of the model utilizing maternal characteristics (AUROC 0.708) and preeclampsia-specific biomarkers (AUROC 0.566). Among the preeclampsia-specific biomarkers, the mean arterial pressure (MAP) contributed to the increasing risk of GDM; however, its addition did not improve the AUROC of the model combining maternal characteristics and obstetric history (0.738). CONCLUSION: The first trimester prediction model for GDM with maternal characteristics and obstetric history achieves moderate predictability. The inclusion of MAP in the model combining maternal characteristics and obstetric history does not improve the screening performance for GDM. Future studies are needed to explore the effect of blood pressure control from early pregnancy on preventing GDM.

The Use of Somatex Shunt for Fetal Pleural Effusion: A Cohort of 8 Procedures.

INTRODUCTION: Fetal pleural effusion may require in utero shunting which is associated with procedure-related complications. OBJECTIVE: To evaluate the efficacy and complications of the newly designed Somatex shunt in treating fetal pleural effusion. METHODS: Consecutive cases with primary fetal pleural effusion who were treated with the Somatex shunt between 2018 and 2019 were evaluated. Perinatal outcomes and complications were retrospectively analyzed. RESULTS: There were 6 cases of unilateral and 1 case of bilateral pleural effusion, and hence a total of 8 pleuroamniotic shunting procedures were performed. The median gestational age at diagnosis and shunting was 20.7 and 22.6 weeks, respectively. All 8 procedures were successful, achieving complete in utero drainage. All but one were live births (85.7%) with a median gestational age of 38 weeks. The single case of in utero death occurred 4.7 weeks after successful shunting, and no cause could be identified after autopsy. The rates of preterm birth and premature rupture of membranes were 33.3% (2/6) and 16.7% (1/6), respectively. Four of the 8 procedures (50%) had minor shunt-related complications such as dislodgement and entrapment, occurring at a median of 7.7 weeks after shunting. None of the shunts became blocked. CONCLUSIONS: The Somatex shunt is effective in relieving fetal pleural effusions with good survival rate. Overall, it was a safe instrument, though minor shunt complications occurred.

Monochorionic twins with selective fetal growth restriction: insight from placental whole-transcriptome analysis.

BACKGROUND: The underlying pathomechanism in placenta-related selective fetal growth restriction in monochorionic diamniotic twin pregnancy is not known. OBJECTIVE: This study aimed to investigate any differences in placental transcriptomic profile between the selectively growth-restricted twins and the normally grown cotwins in monochorionic diamniotic twin pregnancies. STUDY DESIGN: This was a prospective study of monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction. Placental biopsy specimens were obtained from the subjects in the delivery suite. The placental transcriptome of the selectively growth-restricted twin was compared with that of the normally grown cotwin. This study was divided into 2 stages: (1) gene discovery phase in which placental tissues from 5 monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction plus 2 control twin pregnancies underwent transcriptome profiling, and transcriptome profiling was carried out using whole-genome RNA sequencing; and (2) validation phase in which placental tissues from 13 monochorionic diamniotic twin pregnancies with selective fetal growth restriction underwent RNA and protein validation. RNA and protein expression levels of candidate genes were determined using quantitative real-time polymerase chain reaction and immunohistochemistry staining. RESULTS: A total of 1429 transcripts were differentially expressed in the placentae of selectively growth-restricted twin pairs, where 610 were up-regulated and 819 were down-regulated. Endoplasmic reticulum lectin and mannose 6-phosphate receptor were consistently differentially up-regulated in all placentae of selectively growth-restricted twins. Quantitative real-time polymerase chain reaction and immunohistochemistry staining were used to validate the results (P<.05). CONCLUSION: The expression of endoplasmic reticulum lectin and mannose 6-phosphate receptor, which are important for angiogenesis and fetal growth, was significantly increased in the placentae of selectively growth-restricted twin of a monochorionic twin pair.

Placental microRNA dataset of monochorionic twin pregnancies with and without selective fetal growth restriction.

To compare the whole genomic microRNA (miRNA) between the selective fetal growth restriction (sFGR) twin and the normally growing (control) co-twin in monochorionic (MC) twin pregnancies. MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled by microarray. The ratio of the placental miRNA of the sFGR twin to that of the normally larger co-twin were calculated and compared to that of the control twin pairs. The miRNA microarray intensity amongst normal and sFGR large and small twins are shown. The expression data presented here will facilitate other researchers who are working on placental regulation and mechanism in pregnancy complicated by fetal growth restriction. The dataset supports the research article entitle "Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies" [1].

Whole genome miRNA profiling revealed miR-199a as potential placental pathogenesis of selective fetal growth restriction in monochorionic twin pregnancies.

INTRODUCTION: Placental-related mechanism of fetal growth restriction (FGR) is still unknown. Here we aimed to profile whole-genome miRNA between selective FGR twin (sFGR-T) and normally larger co-twin (sL-T) in monochorionic (MC) twin pregnancies and to further investigate effect of the miRNA on placental pathogenesis, including angiogenesis and mitochondrial functions. METHODS: MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled (n = 3 vs 5). Ratio of placental miRNAs in the sFGR twin pairs (sFGR-T/sL-T) were calculated and compared to that in the control twin pairs (cS-T/cL-T). Differentially expressed miRNAs and associated markers were validated qRT-PCR, immunohistochemistry staining (n = 8 vs 13) and electron microscopy (n = 3 vs 3). RESULTS: Placental miR-199a-5p was significantly upregulated in sFGR-T (p = 0.004), which was validated by qRT-PCR (1.03 vs 0.56; p = 0.020). Compared to control twin pairs, ratio of CD31-positive vessels and volume density of vessels in sFGR twin pairs was lower (0.65 vs 0.92 and 18.7% vs 36.3%; both p < 0.001), while that of cyclooxygenase 2 (COX2)-positive trophoblast cells was higher (3.50 vs 2.22; p = 0.001), indicating an impaired angiogenesis and oxidative stress in the sFGR placenta. In addition, ratio of mitochondrial DNA (mtDNA) mitochondrial encoded NADH dehydrogenase 1 (MTND1) copy numbers (2.10 vs 0.90; p = 0.013), H-score ratios of mitochondrial markers citrate synthase (CS) and cytochrome c oxidase subunit 4 isoform 1 (COX4, 0.53 vs 0.95, p < 0.001; 0.29 vs 1.06, p < 0.001) in trophoblast cells of sFGR twin pairs were also altered significantly and correlated with angiogenesis. Furthermore, ratio of mitochondrial numbers per trophoblasts (8.67 vs 18.67; p = 0.006) and percentage of swollen mitochondria (84.33 vs 11.33; p = 0.003) were converted significantly, indicating mitochondrial damage. DISCUSSION: Our results suggested miR-199a-5p may play a role in the placental angiogenesis, oxidative stress and mitochondrial damage and dysfunction as an underlying pathogenesis of sFGR.

Inter-manufacturer comparison of automated immunoassays for the measurement of soluble FMS-like tyrosine kinase-1 and placental growth factor.

OBJECTIVE: To assess inter-manufacturer automated immunoassays for soluble FMS-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF). METHODS: sFlt-1 and PlGF levels were measured using the AutoDelfia PlGF1-2-3 (PerkinElmer Inc. Turku, Finland), BRAHMS Kryptor sFlt-1, PlGF plus and PlGF-2 (BRAHMS ThermoFisher, Germany) and Cobas e411 Elecsys® sFlt-1 and PLGF (Roche Diagnostics GmbH, Mannheim, Germany) in 965 asymptomatic pregnancies between 20 and 39 weeks of gestation and in in-vitro samples with predefined levels of glycosylated PlGF isomers (1, 2 and 3), sFlt-1 in human male serum. Percentage PlGF isoform recovery and cross-reactivities were determined. Paired Bland-Altman and Passing-Bablok analyses were performed to determine bias, precision and accuracy. Inter-manufacturer sFlt-1:PlGF ratio were compared. RESULTS: PlGF-1 isomer recovery ranged from 36 to 39% for Elecsys® to 52-60% for PlGF plus and PlGF-1-2-3 assays. PlGF-2 and PlGF-3 isoform cross-reactivity was assay dependent, ranging from 10 to 21% and 16-36% respectively. BRAHMS PlGF-2 assay had high cross-reactivity to PlGF-1 (37-41%) and PlGF-3 isomers (48-65%). Elecsys® recovery of sFlt-1 was 13% vs 6% for BRAHMS. Passing-Bablok indicated significant proportional and systematic differences between all paired PlGF assay comparisons. PlGF Bland-Altman percentage biases ranged from 12 to 37% for PlGF and 18% for sFlt-1. A linear relationship existed between log transformed sFlt-1:PlGF ratios. The clinical equivalent of the BRAHMS sFlt-1:PlGF plus to the Elecsys® sFlt-1:PlGF ratios of 38 and 110 are 55 and 188 respectively. CONCLUSION: Inter-manufacture immunoassay differences are significantly different. sFlt-1:PlGF rule in/rule out criteria are manufacturer specific, not interchangeable and require separate clinical validation.

Reproductive outcomes after surgical treatment of asherman syndrome: A systematic review.

In this systematic review, we analysed the reproductive outcomes of hysteroscopic adhesiolysis in women with Asherman syndrome (AS). We searched PubMed, Web of Science and Cochrane Library (from database inception to April 2018) and selected studies that quantitatively described the reproductive outcomes. We assessed study quality and pooled rate data for each outcome. There were 54 studies (4640 women) of varying quality. The pooled rate of pregnancy was 50.7% (95% CI [confidence interval]: 49.1 to 52.3) in 53 studies, early pregnancy loss was 17.7% (95% CI: 15.9 to 19.6) in 31 studies, ectopic pregnancy (EP) was 4.2% (95% CI: 2.8 to 6.3) in 9 studies, mid-trimester loss (MTL) was 11.5% (95% CI: 7.6 to 17.8) in 7 studies, cervical incompetence was 12.5% (95% CI: 3.3 to 33.5) in 2 studies and placenta accreta syndrome was 10.1% (95% CI: 8.6 to 11.8) in 23 studies. The pregnancy rate in women with severe adhesion was significantly lower than that in women with mild adhesion (P = 0.021). These results can be used to counsel women with AS before surgical treatment and for planning antenatal care after conception.

Prediction of labor outcome using serial transperineal ultrasound in the first stage of labor.

OBJECTIVE: The objective of this study is to evaluate the feasibility of predicting labor outcome using serial transperineal ultrasound (TPU) in the early active phase of labor. METHODS: This is a single center prospective observational study in a tertiary obstetrics unit in Hong Kong. Nulliparous women carrying singleton pregnancy at the onset of active phase of labor were recruited. Serial 3D volumes by TPU were acquired and then repeated after 1 and 2 h, which were subsequently analyzed for fetal head symphyseal distance (HSD), angle of progression (AoP), and fetal head progression distance (PD). The women were classified into two groups, according to whether they had vaginal delivery or cesarean section (CS) for reasons other than non-progressive labor (Group A) or CS for non-progressive labor (Group B). The TPU parameters were then compared between the groups. RESULTS: Group A consisted of 74 (60.0%) women with vaginal delivery, 27 (21.8%) with instrumental delivery and 3 (2.4%) CS for reasons other than non-progressive labor, while Group B consisted of 20 (16.1%) women who had a CS for non-progressive labor. Group B had a significant slower hourly progression rate of AoP, HSD, and PD at 1-h and 2-h from the initial assessment, compared with Group A. Multivariate logistic regression analysis demonstrated that PD progression at 2-h and the use of oxytocin were significant independent predictors for CS for non-progressive labor. CONCLUSION: It is feasible to predict CS for non-progressive labor in the early active phase of labor by a slower rate of fetal head descent determined by TPU.

Body mass index at 11-13 weeks' gestation and pregnancy complications in a Southern Chinese population: a retrospective cohort study.

OBJECTIVE: To assess the association between body mass index (BMI) and adverse pregnancy outcomes. MATERIALS AND METHODS: A multicentre retrospective cohort study was conducted in three hospitals in Hong Kong including 67,248 women with singleton pregnancy at 11-13 weeks between 2010 and 2016. The relationship between maternal BMI and (1) miscarriage or stillbirth, (2) development of preeclampsia (PE), (3) gestational hypertension (GH), (4) development of gestational diabetes mellitus (GDM), (5) spontaneous preterm delivery (sPTD) <34 and <37 weeks, (6) delivery of a small for gestational age (SGA) or large for gestational age (LGA) neonate, (7) caesarean section (CS), and (8) postpartum haemorrhage (PPH) were examined after adjusting for confounding factors. RESULTS: The prevalence of maternal overweight (BMI 25-29.9 kg/m2) and obesity (BMI ≥30 kg/m2) were 13.2% and 2.9%, respectively. Women with a BMI ≥30 kg/m2 were nine times more likely to develop GH (95%CI 7.3-11.7), five times more likely to develop PE (95%CI 4.3-6.8) and GDM (95%CI 5.0-6.5) and 1.5-2 times more likely to deliver SGA/LGA neonate. sPTD, required delivery by CS and developed PPH, than those with a BMI of 18.5-22.9 kg/m2, and that maternal underweight (BMI <18.5 kg/m2) significantly reduced the risk of GDM, delivery by CS, and PPH. Increased risk of subsequent development of adverse outcomes was observed when BMI was ≥23.0 kg/m2. CONCLUSIONS: Maternal overweight and obesity are associated with an increased risk for subsequent development of various pregnancy complications. The need of increased awareness and health surveillance is essential when BMI ≥23 kg/m2.