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.

Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal-fetal interface following SARS-CoV-2 infection.

During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

Evaluation of first trimester maternal serum inhibin-A for preeclampsia screening.

BACKGROUND: International professional organizations recommend aspirin prophylaxis to women screened high risk for preterm preeclampsia (PE) in the first trimester. The UK Fetal Medicine Foundation (FMF) screening test for preterm PE using mean arterial pressure (MAP), uterine artery pulsatility index (UTPI) and placental growth factor (PlGF) was demonstrated to have lower detection rate (DR) in Asian population studies. Additional biomarkers are therefore needed in Asian women to improve screening DRs as a significant proportion of women with preterm and term PE are currently not identified. OBJECTIVES: To evaluate maternal serum inhibin-A at 11-13 weeks as an alternative to PlGF or as an additional biomarker within the FMF screening test for preterm PE. STUDY DESIGN: This is a nested case-control study using pregnancies initially screened at 11-13 weeks for preterm PE using the FMF triple test in a non-intervention study conducted between December 2016 and June 2018. Inhibin-A levels were retrospectively measured in 1,792 singleton pregnancies, 112 (1.7%) with PE matched for time of initial screening with 1,680 unaffected pregnancies. Inhibin-A levels were transformed to multiple of the expected median (MoM). The distribution of log10 inhibin-A MoM in PE and unaffected pregnancies and the association between log10 inhibin-A MoM and gestational age (GA) at delivery in PE were assessed. The screening performance determined by area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR), for preterm and term PE was determined. All risks for preterm and term PE were based on the FMF competing risk model and Bayes theorem. Differences in AUC (ΔAUC) between different biomarker combinations were compared using the Delong test. McNemar's test was used to assess the off-diagonal change in screening performance at a fixed 10% FPR after adding inhibin-A or replacing PlGF in the preterm PE adjusted risk estimation model. RESULTS: Inhibin-A levels in unaffected pregnancies were significantly dependent on GA, maternal age and weight and were lower in parous women with no previous history of PE. Mean log10 inhibin-A MoM in any-onset PE (p<0.001), preterm (p<0.001) and term PE (p = 0.015) pregnancies were all significantly higher than that of unaffected pregnancies. Log10 inhibin-A MoM was inversely but not significantly correlated (p = 0.165) with GA at delivery in PE pregnancies. Replacing PlGF with inhibin-A in the FMF triple test reduced AUC and DR from 0.859 and 64.86% to 0.837 and 54.05%, the ΔAUC was not statistically significant. AUC and DR when adding inhibin-A to the FMF triple test were 0.814, 54.05% and the -0.045 reduction in AUC was statistically significant (p = 0.001). At a fixed 10% FPR, replacing PlGF with inhibin-A identified 1 (2.7%) additional pregnancy but missed 5 (13.5%) pregnancies which subsequently developed preterm PE identified by the FMF triple test. Adding inhibin-A missed 4 (10.8%) pregnancies and did not identify any additional pregnancies with preterm PE. CONCLUSION: Replacing PlGF by inhibin-A or adding inhibin-A as an additional biomarker in and to the FMF triple screening test for preterm PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Cat-Ear-Line: A Sonographic Sign of Cortical Development?

OBJECTIVES: Diagonal echogenic lines outside the lateral ventricle have often been observed in the anterior coronal planes of the normal fetal brain by neurosonography. We have observed abnormal shapes of these echogenic lines in cases of malformation of cortical development (MCD). We named the ultrasound finding "cat-ear-line" (CEL). This study aimed to examine how and when CEL develops in normal cases compared with MCD cases. METHODS: We retrospectively examined the fetal brain volume dataset acquired through transvaginal 3D neurosonography of 575 control cases and 39 MCD cases from 2014 to 2020. We defined CEL as the hyperechogenic continuous lines through subplate (SP) and intermediate zone (IZ), pre-CEL as the lines that existed only within the SP, and abnormal CEL as a mass-like or mosaic shadow-like structure that existed across the SP and IZ. All fetuses in the MCD group had some neurosonographic abnormalities and were ultimately diagnosed with MCD. RESULTS: The CEL was detected in 97.9% (369/377) of the control group from 19 to 30 weeks. The CEL visualization rate of the MCD group in the same period was 40.0% (14/35) which was significantly lower than that of the control group (P < .001). CONCLUSIONS: From this study, it appears that the CEL is an ultrasound finding observed at and beyond 19 weeks in a normally developing fetus. In some MCD cases, pre-CEL at and beyond 19 weeks or abnormal CEL was observed. Maldeveloped CEL at mid-trimester may help identify cases at-risk of subsequent MCD.

Maternal iron kinetics and maternal-fetal iron transfer in normal-weight and overweight pregnancy.

BACKGROUND: Inflammation during pregnancy may aggravate iron deficiency (ID) by increasing serum hepcidin and reducing iron absorption. This could restrict iron transfer to the fetus, increasing risk of infant ID and its adverse effects. OBJECTIVES: We aimed to assess whether iron bioavailability and/or iron transfer to the fetus is impaired in overweight/obese (OW) pregnant women with adiposity-related inflammation, compared with normal-weight (NW) pregnant women. METHODS: In this prospective study, we followed NW (n = 43) and OW (n = 40) pregnant women who were receiving iron supplements from the 14th week of gestation to term and followed their infants to age 6 mo. We administered 57Fe and 58Fe in test meals mid-second and mid-third trimester, and measured tracer kinetics throughout pregnancy and infancy. RESULTS: In total, 38 NW and 36 OW women completed the study to pregnancy week 36, whereas 30 NW and 27 OW mother-infant pairs completed the study to 6 mo postpartum. Both groups had comparable iron status, hemoglobin, and serum hepcidin throughout pregnancy. Compared with the NW, the OW pregnant women had 1) 43% lower fractional iron absorption (FIA) in the third trimester (P = 0.033) with median [IQR] FIA of 23.9% [11.4%-35.7%] and 13.5% [10.8%-19.5%], respectively; and 2) 17% lower maternal-fetal iron transfer from the first tracer (P = 0.051) with median [IQR] maternal-fetal iron transfer of 4.8% [4.2%-5.4%] and 4.0% [3.6%-4.6%], respectively. Compared with the infants born to NW women, infants born to OW women had lower body iron stores (BIS) with median [IQR] 7.7 [6.3-8.8] and 6.6 [4.6-9.2] mg/kg body weight at age 6 mo, respectively (P = 0.024). Prepregnancy BMI was a negative predictor of maternal-fetal iron transfer (ß = -0.339, SE = 0.144, P = 0.025) and infant BIS (ß = -0.237, SE = 0.026, P = 0.001). CONCLUSIONS: Compared with NW, OW pregnant women failed to upregulate iron absorption in late pregnancy, transferred less iron to their fetus, and their infants had lower BIS. These impairments were associated with inflammation independently of serum hepcidin.This trial was registered at clinicaltrials.gov as NCT02747316.

Assessment of embryo morphology following perinatal exposure to aspirin, ibuprofen and paracetamol using whole embryo culture system.

BACKGROUND: Recent evidence from a meta-analysis indicates that maternal prenatal exposure, single or repeated, to non-steroidal anti-inflammatory drugs (NSAIDs) or non-opioid painkillers, is associated with increased risk of cerebral palsy and cognitive-behavioral disorders in offspring. One potential route of action is interference with the neurulation process and hence early brain development. OBJECTIVE: To examine the effect of prenatal exposure to common NSAIDs and non-opioid drugs on neurulation using an in vitro whole embryo culture system. METHODS: Mouse embryos from in-bred Institute of Cancer Research albino strain mice were exteriorized on embryonic day 7.5 and cultured for 48 h in either 1 mL heat-inactivated rat serum + 0.1% dimethyl sulfoxide ("Control") or 1 mL of rat serum supplemented with six increasing concentrations of laboratory-grade aspirin, paracetamol, and ibuprofen ("Experimental"). After culture, embryo morphological and developmental parameters were documented using standardized scoring systems at each dosage concentration. The assessed concentration in rat serum culture ranged from 1.23 to 13.57 mg/mL for aspirin and 0.06-4.93 mg/mL for paracetamol and ibuprofen. The equivalent respective human dosages were 600-6600 mg and 30-2400 mg. RESULTS: Between-group comparisons ("Control" vs "Experimental") and post-hoc pair-wise tests, adjusted for multiple comparisons, indicating no statistically significant effect on crown-rump length (p > .21), head length (p > .28), somite number (p > .25), incidence of absent hindlimb buds (p > .18), yolk sac circulation score (p > .07) and posterior neuropore closure (p > .35) in the aspirin, paracetamol and ibuprofen experiments. All embryos had forelimb buds, closed anterior neuropores and none had neural tube defects. CONCLUSION: This study has demonstrated that there are no safety concerns regarding high-dose aspirin, ibuprofen, and paracetamol on mice's embryonic development.

Correction: Seroprevalence of Zika virus in pregnant women from central Thailand.

[This corrects the article DOI: 10.1371/journal.pone.0257205.].

Additional benefits of three-dimensional ultrasound for prenatal assessment of twins.

Three-dimensional ultrasound (3DUS) may provide additional information for prenatal assessment of twins. It may improve the diagnostic confidence of dating, nuchal translucency (NT) and chorionicity assignment in twin pregnancies. The "virtual 3DUS placentoscopy" can guide selective fetoscopic laser photocoagulation (SFLP) to treat twin-twin transfusion syndrome (TTTS). Volumetric assessment of the dysmorphic acardiac twin with the Virtual Organ Computer-aided Analysis (VOCAL) software is more accurate than the conventional ultrasound measurement. Twin anemia polycythemia (TAP) sequence and selective intrauterine growth restriction (sIUGR) may be clinically monitored with 3DUS placental volume (PV) and power Doppler vascular indices. Congenital anomalies are more common in twins. Evaluation of fetal anomalies with 3DUS could assist perinatal management. The 3DUS power Doppler can provide a better understanding of true and false umbilical cord knots, which are commonly found in monoamniotic (MA) twins. Single demise in monochorionic (MC) twin pregnancies can cause severe neurologic morbidity in the surviving co-twin. Prenatal prediction of brain injury in the surviving co-twin with unremarkable neurosonographic examination is difficult. The 3DUS power Doppler may aid in prenatal detection of subtle abnormal cerebral perfusion. Prenatal assessment of conjoined twins with 3DUS is important if emergency postnatal surgical separation is anticipated. There is no significant additional advantage in using real-time 3DUS to guide prenatal interventions. Assessment of the cervix and pelvic floor during twin pregnancies is enhanced with 3DUS. Due to lack of high-quality studies, routine prenatal 3DUS in twin pregnancies needs to be balanced with risks of excessive ultrasound exposure.

Cervical shear wave elastography as a predictor of preterm delivery during 18-24 weeks of pregnancy.

AIM: The aim of this study was to compare shear wave cervical elasticity between term and preterm delivery group. METHODS: A prospective cohort study was conducted in enrolled 158 pregnant women at 18-24 weeks of gestation who come for second trimester scan consecutively. Transvaginal ultrasonography for cervical length as well as cervical elasticity in five regions of interest was performed. Intraobserver and interobserver reproducibility were evaluated. Gestational age at deliveries was followed, and cervical shear wave elasticity between term and preterm group was compared. RESULTS: A total of 158 pregnant women were enrolled in this study while 120 pregnancies data were collected for subsequent analysis, 10 pregnancies spontaneously delivered during the preterm period and 110 pregnancies delivered at term. Intraobserver and interobserver reproducibility were high; however, cervical shear wave elasticity in both groups were not significantly different (external anterior lip 2.29 ± 0.66 and 2.45 ± 0.58 m/s, P value 0.30, internal anterior lip 2.74 ± 0.96 and 2.80 ± 0.61 m/s, P value 0.83). Nonsignificant correlations of cervical shear wave elasticity with gestational age and cervical length (r = -0.1 and r = 0.02, respectively) were demonstrated. CONCLUSION: Cervical shear wave elasticity in preterm and term groups was not significantly different when measured at 18-24 weeks of gestation. There are nonsignificant correlations between cervical shear wave elasticity, gestational age and cervical length. Cervical shear wave elastography alone should not be used as a predictor for preterm delivery.