Clinical practice guidelines for intrapartum cardiotocography interpretation: A systematic review.

BACKGROUND: Clinical practice guidelines on intrapartum cardiotocography (CTG) interpretation provide structured tools to detect fetal hypoxia. Despite frequent use of different guidelines, little is known about their comparable consistency. We sought to appraise guidelines relevant to intrapartum CTG interpretation and summarise consensus and non-consensus recommendations. AIMS: To compare existing intrapartum CTG interpretation guidelines. MATERIALS AND METHODS: We searched PubMed, CINAHL, Cochrane, Embase, guideline databases and websites of guideline development institutions using terms 'cardiotocography', 'electronic fetal/foetal monitoring', and 'guideline' or equivalent term. The search was restricted to English-language articles published between January 1980 and January 2023 and excluded animal studies. The initial search yielded 2128 articles with 1253 unique citations. Guidelines were included if they: used English as the reporting language; included CTG interpretation criteria or guidelines as a primary objective; were published or updated since 1980; and were the most recently updated publications when multiple versions were identified. RESULTS: Nineteen studies were considered for full review, and 13 met inclusion criteria. Two reviewers independently assessed guideline quality using the AGREE II instrument, and synthesised consensus and non-consensus recommendations using the content analysis approach. Most guidelines employed a three-tier interpretation framework. There were significant differences between the guidelines for relative importance of key CTG features such as accelerations, decelerations and variability, with respect to the outcome of fetal hypoxia. CONCLUSIONS: There are significant differences between key intrapartum CTG interpretation guidelines currently being used. Greater consistency is needed across CTG interpretation guidelines to improve the quality of data, clinical governance, monitoring of outcomes, and to support future developments.

Lipiodol flushing under ultrasound guidance at time of hystero-salpingo contrast sonography (HyCoSy): A retrospective observational study.

BACKGROUND: Up to 30% of female infertility can be attributed to tubal abnormalities. Assessment of fallopian tube patency forms a component of the basic assessment of infertility. Tubal patency can be checked through hysterosalpingogram (HSG) under radiologic guidance with oil- or water-based contrast medium (OBCM or WBCM), or hystero-salpingo contrast sonography (HyCoSy) under ultrasound guidance with WBCM. Tubal flushing with OBCM has been shown to improve fertility rates. OBJECTIVES: To study the feasibility and tolerability of performing Lipiodol (ethiodised oil) flush concurrently with HyCoSy. To examine the in vivo sonographic visibility of Lipiodol vs normal saline. MATERIALS AND METHODS: Retrospective observational study of patients with subfertility referred for Lipiodol flushing under ultrasound guidance between August 2017-September 2020 at six private ultrasound practices in Sydney, Australia. RESULTS: There were 412 patients who were referred for Lipiodol flushing. Of these, 86 patients did not have concurrent Lipiodol flush at HyCoSy performed due to strict exclusion criteria. Of the 326 patients who proceeded with Lipiodol flushing at HyCoSy, all cases were successful, with no cases of extravasation. There were no major complications. In vivo sonographic visualisation of Lipiodol was similar to that of the commonly used agitated 0.9% saline (n = 20; mean visibility score 4.3 ± 0.9 vs 4.0 ± 1.2). CONCLUSION: Our study has shown that Lipiodol flushing at time of HyCoSy as a single procedure is feasible and tolerable to patients. Flushing with Lipioidol during HyCoSy is likely as sonographically visible as 0.9% saline.

Outcomes and success of new tiered perinatal transfer policy within a tertiary level obstetric unit in Australia.

BACKGROUND: New South Wales Health introduced the new Tiered Networking Arrangements for Perinatal Care in New South Wales policy directive (TPN Policy), which defined key performance and quality indicators after implementation. AIMS: This study aims to assess the success of the TPN Policy implementation in the Western Sydney TPN in accordance with key performance indicators. MATERIALS AND METHODS: This is a retrospective cohort study of acute perinatal transfers within the Western Sydney TPN between 1 December 2019 to 31 December 2020. The primary outcome is compliance with objectives of the TPN Policy, as measured as an Aggregate Compliance Score comprising the five measures. Secondary outcomes include clinical, neonatal and logistics outcomes. RESULTS: There were 181 acute perinatal transfers within, into or out of the Western Sydney TPN between 1 December 2019 to 31 December 2020. There were 122 transfers within the network, 40 into the TPN and 19 were out of the TPN. All groups were at least partially compliant with the TPN Policy. No transfers in any of groups scored below three ('partially compliant'). A quarter of transfers gave birth within 24 h of transfer. Over half of those who were transferred and admitted went on to give birth prior to discharge or transfer. CONCLUSIONS: Overall, the TPN Policy met its objectives after implementation in the Western Sydney TPN, while maintaining appropriate neonatal outcomes. All women arrived at an appropriate facility prior to giving birth, although the majority did not give birth within 24 h. Neonatal intensive care unit bed availability is a key limitation to future improvement.

Aspirin for the prevention of pre-eclampsia in women with pre-existing diabetes: Systematic review.

BACKGROUND: There is a lack of evidence for pre-eclampsia prophylaxis with aspirin in women with pre-existing diabetes mellitus (DM). AIMS: To examine the evidence for aspirin in pre-eclampsia prophylaxis in women with pre-existing DM. MATERIAL AND METHODS: An electronic search using Ovid MEDLINE, Embase, CinicalTrials.gov and the Cochrane CENTRAL register of controlled trials through to February 2021 was performed. Reference lists of identified studies, previous review articles, clinical practice guidelines and government reports were manually searched. Randomised controlled trials (RCTs) of aspirin vs placebo for pre-eclampsia prophylaxis were included. Articles were manually reviewed to determine if cohorts included women with DM. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data from included trials were extracted independently by two authors who also independently assessed risk of bias as per the Cochrane Handbook criteria version 5.1.0. Data were analysed using Rev-Man 5.4. RESULTS: Forty RCTs were identified, of which 11 included a confirmed subset of women with DM; however, data were insufficient for meta-analysis. Meta-analysis of 930 women with DM, from individual patient data included in a systematic review and unpublished data from one of the 11 RCTs, showed a non-significant difference in the outcome of pre-eclampsia in participants treated with aspirin compared to placebo (odds ratio 0.58; 95% CI 0.20-1.71; P = 0.33). CONCLUSIONS: Pre-eclampsia risk reduction with aspirin prophylaxis in women with pre-existing DM may be similar to women without pre-existing DM. However, randomised data within this meta-analysis were insufficient, warranting the need for further studies within this high-risk group of women.

Perinatal and Child Factors Mediate the Association between Preeclampsia and Offspring School Performance.

OBJECTIVE: To determine whether maternal preeclampsia is an independent risk factor for poorer academic school performance in offspring, taking into account important perinatal and child factors. STUDY DESIGN: A population-based cohort study using record-linkage of state-wide data was undertaken. We evaluated children born at 28+ weeks of gestation in New South Wales, Australia who had grade 3 record-linked education outcomes via the National Assessment Program-Literacy and Numeracy (NAPLAN) between 2009 and 2014. Children with in utero preeclampsia exposure were compared with those without exposure. Robust multivariable Poisson models were used to determine adjusted relative risks. RESULTS: Crude models demonstrated an increased risk of scoring below the national minimal standard in all 5 domains (reading, writing, spelling, grammar and punctuation, and numeracy) for children exposed to preeclampsia, ranging from a relative risk (RR) of 1.13 (95% CI, 1.04-1.24) for reading to 1.19 (95% CI, 1.09-1.30) for numeracy. These differences were attenuated once adjusted for perinatal and child factors (RR, 1.07 [95% CI, 0.97-1.18] to 1.11 (95% CI, 0.99-1.22]), with combined perinatal and childhood factors mediating between 35.7% (writing) to 55.1% (spelling) of the association. Gestational age at birth was the most important perinatal factor, explaining 10.5% (grammar and punctuation) to 20.6% (writing) of the association between preeclampsia and poor school performance, followed by small for gestational age. CONCLUSION: The poorer educational performance experienced by children born to women with preeclampsia appears largely attributable to perinatal and childhood factors, suggesting an opportunity to improve school performance in children exposed to preeclampsia by optimizing these perinatal factors, particularly gestational age at birth.

Association of Preeclampsia With Myocardial Injury Among Patients Undergoing Noncardiac Surgery: The PREECLAMPSIA-VISION Study.

BACKGROUND: In women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality. METHODS: This study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery. RESULTS: Analyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality. CONCLUSIONS: Preeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women.

Twin anemia polycythemia sequence in dichorionic diamniotic twins: A case report and review of the literature.

Although rare, literature demonstrates evidence that vascular anastomoses do occur in dichorionic twins. Therefore, twin anemia polycythemia sequence should be considered as a differential diagnoses in dichorionic twins if there is suspicion on antenatal ultrasound.

Lipiodol visibility under ultrasound.

BACKGROUND: Lipiodol is an oil-based solution commonly used in hysterosalpingogram (HSG), but not hysterosalpingo contrast sonography (HyCoSy). In women with unexplained infertility, evidence suggests that tubal flushing with Lipiodol results in improved fertility post-procedure. We propose that Lipiodol can be visualised under ultrasound similar to commonly used saline, and hence utilised for HyCoSy, allowing the benefit of an oil-based tubal flushing to occur with HyCoSy. AIMS: To examine whether Lipiodol is visible sonographically, assess optimal agitated Lipiodol mix and ultrasound settings for visibility, and compare visibility to agitated saline, routinely used for HyCoSy. MATERIALS AND METHODS: Two separate sonographers with identical ultrasound machines and model pelvises recorded images with varying degrees of agitated Lipiodol and ultrasound settings, in addition to capturing images with no fluid and agitated saline. Each test was performed in quadruplicate and in random order. Images were read by 47 blinded reporters and visibility reported on a scale of one (not visible) to five (clearly visible). RESULTS: The mean visibility score for images captured where the Lipiodol sample was agitated five times prior to injection to allow the formation of air microbubbles, regardless of ultrasound setting, were higher than or not different from that for agitated saline (all P > 0.7 when not different, <0.001 when higher). CONCLUSIONS: Sonographic visualisation of agitated Lipiodol is similar or better than that of agitated saline. Lipiodol may therefore present a possibility for use with HyCoSy, with the added benefit of oil-based tubal flushing, avoiding the radiation exposure of HSG and concurrently providing pelvic soft-tissue evaluation.

Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction.

OBJECTIVE: To determine the correlation between urinary and serum placental growth factor (PlGF) and investigate the predictive value as pregnancy progresses of urinary PlGF compared with serum PlGF, soluble fms-like tyrosine kinase 1 (sFLT-1), and the sFLT-1-to-PlGF ratio for the outcome of preeclampsia in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: A multicenter prospective cohort study was conducted of 158 women with preexisting insulin-requiring diabetes (41 with type 1 and 117 with type 2). Urinary PlGF and serum PlGF, sFLT-1, and the sFLT-1-to-PlGF ratio were assessed four times (14, 24, 30, and 36 weeks' gestation), and the association with the outcome of preeclampsia was investigated. RESULTS: A correlation between urinary and serum PlGF was demonstrated from 24 weeks' gestation onward (P < 0.001). At all time points, those who developed preeclampsia had lower serum PlGF levels (P < 0.05), and receiver operating characteristic curves demonstrated that serum PlGF in this cohort performed better than the serum sFLT-1-to-PlGF ratio as a predictive test for preeclampsia. Preconception HbA1c ≥6.5% (48 mmol/mol) was an important discriminative predictor for preeclampsia (P = 0.01). CONCLUSIONS: This study prospectively describes the longitudinal changes in urinary PlGF alongside serum angiogenic markers throughout pregnancy in women with preexisting diabetes. We demonstrate correlation between urinary and serum PlGF and that in women with preexisting diabetes in pregnancy, serum PlGF is a better predictor of preeclampsia than the sFLT-1-to-PlGF ratio.

Urinary placental growth factor in preeclampsia and fetal growth restriction: An alternative to circulating biomarkers?

AIM: To correlate plasma and urinary soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in preeclampsia (PE) and fetal growth restriction (FGR) and assess the performance in detecting established disease. METHODS: A cross-sectional case-control study recruited 26-40 weeks gestation pregnancies into four clinical groups: normal pregnancy, PE, PE + FGR, and FGR. enzyme-linked immunosorbent assay (ELISA) measurements of urinary and plasma sFlt-1 and PlGF levels were performed. Urinary levels of sFlt-1 and PIGF were normalized to creatinine. Spearman's rank correlation was used to assess the association between plasma and urinary levels of sFlt-1 and PIGF, and receiver operating characteristic graphs were used to quantify the performance of each individual marker and their ratios in predicting normal versus pathological pregnancies affected by preeclampsia and/or FGR. RESULTS: There was a significant correlation between plasma PlGF and urinary PlGF (r = 0.718, P < 0.001) in all groups. In the pathological groups, plasma sFlt-1 and urinary sFlt-1 as well as plasma sFlt-1: PIGF ratio and urinary sFlt-1: PlGF ratio were higher, but plasma PIGF and urinary PlGF were lower when compared to normal pregnancy. Plasma PIGF and plasma sFlt-1: PlGF ratio was comparable in performance to urinary PlGF and urinary sFlt-1: PIGF ratio for the diagnosis of preeclampsia and/or FGR. CONCLUSION: Urinary PIGF can be used as an alternative to circulating biomarkers in preeclampsia and FGR. Plasma sFlt-1, PlGF and sFlt-1: PlGF ratio as well as urinary PIGF and sFlt-1: PlGF ratio can be used to differentiate between normal pregnancy and pregnancies complicated by preeclampsia and FGR.

Microalbuminuria as an early predictor of preeclampsia in the pre-gestational diabetic population: A prospective cohort study.

OBJECTIVES: To determine if microalbuminuria can be used as a predictive marker of preeclampsia and adverse pregnancy and neonatal outcomes in women with pre-existing diabetes and to compare the prognostic utility of urinary albumin to creatinine ratio (uACR) and urinary protein to creatinine ratio (uPCR). STUDY DESIGN: Multicentre prospective cohort study. Antenatal Diabetes in Pregnancy clinics at three tertiary referral hospitals in Western Sydney, Australia. 158 women with pre-existing diabetes requiring insulin in pregnancy. A spot uPCR and uACR was performed in each trimester. Pregnancy and fetal outcomes were investigated using linear models and receiver-operating characteristic (ROC) curves. MAIN OUTCOME MEASURES: The primary outcome was preeclampsia (PE). Secondary outcomes investigated were other adverse pregnancy and neonatal outcomes. RESULTS: Increased levels of both uPCR and uACR in trimester 3 were associated with the occurrence of PE (p = 0.007, 0.010 respectively). In the 113 patients with normal pregnancy uPCR (<30 mg/mmol) in trimester 1, microalbuminuria was found to be predictive of PE (p = 0.01) and need for operative delivery (p = 0.03). CONCLUSIONS: In women with pre-existing diabetes, uPCR and uACR appear to have similar ability to diagnose PE, but microalbuminuria demonstrates prognostic ability at a much earlier gestation, prior to the onset of other signs or symptoms of PE. We therefore suggest that assessing microalbuminuria rather than overt proteinuria in trimester 1 provides prognostic information in women with pre-existing diabetes requiring insulin and should be used routinely to evaluate risk of PE in this high-risk cohort of women.

Pre-existing diabetes in pregnancy.

The incidence of type 1 and type 2 diabetes amongst women of reproductive age is increasing worldwide. Despite recent advances in treatment options for diabetes outside of pregnancy, women still have a significantly increased risk of adverse obstetric outcomes including perinatal death and congenital malformation, compared to the non-diabetic population. An understanding of the physiological changes during pregnancy, management, early detection and prevention of complications and pre-pregnancy care, specific to women with pre-existing diabetes, is important in improving health outcomes in this growing group of women. This review particularly focuses on areas where there have been recent developments or controversy.

Pre-existing diabetes in pregnancy.

The incidence of type 1 and type 2 diabetes amongst women of reproductive age is increasing worldwide. Despite recent advances in treatment options for diabetes outside of pregnancy, women still have a significantly increased risk of adverse obstetric outcomes including perinatal death and congenital malformation, compared to the non-diabetic population. An understanding of the physiological changes during pregnancy, management, early detection and prevention of complications and pre-pregnancy care, specific to women with pre-existing diabetes, is important in improving health outcomes in this growing group of women. This review particularly focuses on areas where there have been recent developments or controversy.

The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.

Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.