Intrapartum fetal heart rate monitoring: Rationalise, refine or replace?

Monitoring the fetal heartbeat underpins assessment of fetal wellbeing in labour. Although commonly employed in clinical practice, shortcomings remain. A recent review of clinical practice guidelines highlights the variation in definitions of the fetal heart rate that will lead to differences in interpretation. Will intrapartum care be improved by greater consensus around clinical practice guidelines through rationalisation or refinement of guidelines, or will the future see this technique replaced by more accurate forms of fetal monitoring?

Pre-eclampsia in a first pregnancy and subsequent pregnancy outcomes: a nationwide cohort study.

BACKGROUND: For women whose first pregnancy was complicated by pre-eclampsia (PE), particularly if severe and requiring early birth, the risk of recurrence and maternal and neonatal outcomes at subsequent birth are important considerations. METHODS: In this observational cohort study, all primiparous women who gave birth in Denmark between 1997 and 2016 were identified using nationwide registries. Women were stratified by whether they developed PE and followed from date of birth until subsequent birth, emigration, death or end of study (December 2016). The cumulative incidences of subsequent birth among women with versus without PE were assessed using the Aalen-Johansen estimator. Subsequent outcomes including PE recurrence and maternal and neonatal morbidity and mortality were also examined. Factors associated with subsequent birth and recurrent PE were examined using multivariable Cox regression models. RESULTS: Among 510 615 primiparous women with singleton pregnancies, 21 683 (4.2%) developed PE, with 1819 (0.4%) being early-onset PE (birth <34 weeks). Women with PE had a lower subsequent birth rate (57.4%) compared with women without PE (61.2%), and it was considerably lower among women with early-onset PE (49.4%). Among women with PE who had a subsequent birth, the overall recurrence rate of PE was 15.8% and higher among those with early-onset PE (31.5%). The gestational age increased with a median of 3 days (IQR -5 to 14) overall and 50 days (IQR 35-67) among those with early-onset PE. Moreover, neonatal and maternal morbidity and mortality were substantially improved in a subsequent pregnancy. CONCLUSIONS: Primiparous women with PE have a significantly lower rate of a subsequent birth than women without PE, yet the absolute difference was modest. Although the overall risk of recurrent PE is 1 in 6, maternal and neonatal morbidity and mortality at subsequent birth are substantially improved.

Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Vernix Caseosa Peritonitis Causing Acute Abdomen After Cesarean Section: A Case Series.

BACKGROUND Vernix caseosa peritonitis (VCP) is a rare complication that typically presents following an otherwise uneventful cesarean section. Leakage of vernix caseosa into the peritoneum is thought to elicit a granulomatous foreign body reaction. Symptoms can be similar to other acute abdominal conditions, and diagnosis is confirmed by intraoperative findings and histological examination. Peritoneal lavage with supportive measures is the mainstay of treatment and recovery. CASE REPORT Case 1 was a 30-year-old woman who developed right iliac fossa pain, fever, tachycardia, and tachypnea less than a week after her lower segment cesarean section (LSCS). She underwent a laparoscopy for a peritonitic abdomen and concern for intra-abdominal sepsis. A peritoneal biopsy demonstrated histological changes consistent with VCP. Case 2 was a 39-year-old woman who underwent a LSCS. After discharge, she re-presented with generalized abdominal pain. With computed tomography (CT) scan findings suggestive of appendicitis, an appendectomy was performed, and vernix caseosa was detected in all quadrants. Case 3 was a 33-year-old woman who presented with fever, vomiting, diarrhea, and iliac fossa pain 9 days following an LSCS. She was given analgesia and antibiotics for a pelvic fluid collection noted on CT scan. She re-presented with tense swelling and pain above her cesarean section incision. Laparoscopy revealed adhesions over the lower abdomen and pelvis and white plaques suggestive of vernix caseosa along the peritoneal side walls. CONCLUSIONS The rising incidence of cesarean births worldwide creates the potential for increased numbers of VCP cases. Greater recognition of VCP is warranted to prevent unnecessary procedures.

Staged treatment of placenta accreta spectrum: A combined surgical and radiological approach.

BACKGROUND: Placenta accreta spectrum (PAS) is a rare but serious complication of pregnancy. AIMS: The aim of this study was to determine maternal and neonatal outcomes following a combined surgical and interventional radiology (IR) approach to managing PAS, and the risks associated with this technique. METHODS AND MATERIALS: Retrospective cohort study of all cases of PAS in a tertiary maternity centre between January 2001 and July 2020. Women who underwent caesarean hysterectomy for histologically confirmed PAS with a staged surgical and IR approach were compared with those who underwent caesarean hysterectomy without IR. Maternal, neonatal outcomes, surgical and radiological complications were assessed. RESULTS: Forty-six women were included in the study, and 30/46 (65.2%) underwent the staged surgical and IR approach. Women in the staged group had less overall blood loss (1794 mL vs 3713 mL; P < 0.001), less requirement for blood transfusion (40% vs 75%; P < 0.001), and a lower mean volume of packed red cells transfused (2.5 vs 6.1 units). Anaesthetic and operative times were longer for the staged group (468 vs 189 min: 272 vs 141 min P < 0.001), respectively. There were no differences in rates of neonatal or maternal complications between the two groups. CONCLUSION: This study demonstrates that a staged procedure combining surgery and IR for PAS results in a considerable reduction in blood loss, need for transfusion, and units of packed red cells transfused compared with surgery alone. The staged procedure required significantly longer anaesthetic and operative times; however, there were no differences in maternal and neonatal morbidity.

COVID-19 vaccine acceptance among pregnant women and the reasons for hesitancy: A multi-centre cross-sectional survey.

BACKGROUND: On 9 June 2021, the Australian Technical Advisory Group on Immunisation and Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommended that pregnant women receive Comirnaty (Pfizer) messenger RNA vaccine at any stage of pregnancy. AIM: This multi-centre study aimed to assess vaccine acceptance, reasons for hesitancy and determine if differences exist between health districts, to inform future policy strategies for COVID-19 vaccination in pregnancy. MATERIALS AND METHODS: An online survey (developed based on the World Health Organization Behavioural and Social Drivers survey and modified for the pregnant population) was administered to a sample population of pregnant women attending antenatal clinics at two metropolitan hospitals (Westmead and Royal North Shore Hospital (RNSH)) in New South Wales between 15 September 2021 and 22 October 2021. RESULTS: There were 287 pregnant women surveyed (Westmead 198 (69%), RNSH 66 (23%), no site 23 (8%)). There was a significantly lower Socio-Economic Indexes for Areas score (5.66 vs 9.45, P = 0.001), fewer women born in Australia (37% vs 53%, P = 0.02) and higher number of children (0.77 vs 0.41, P = 0.01) among Westmead respondents. There was lower vaccination uptake (68% vs 86%, P = 0.01) and willingness to receive vaccine (68% vs 88% P = 0.01) at Westmead compared to RNSH. There was an increased proportion of respondents who were concerned that the vaccine could cause harm to the unborn baby at Westmead (38% vs 11%, P = 0.01). CONCLUSIONS: Along with healthcare provider recommendation for vaccination in pregnancy, materials should be targeted to specific safety concerns of pregnant women.

Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction.

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease.

Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Maternal and neonatal outcomes of women with gestational diabetes and without specific medical conditions: an Australian population-based study comparing induction of labor with expectant management.

BACKGROUND/AIMS: To evaluate maternal birth and neonatal outcomes among women with gestational diabetes mellitus (GDM), but without specific medical conditions and eligible for vaginal birth who underwent induction of labour (IOL) at term compared with those who were expectantly managed. MATERIALS AND METHODS: Population-based cohort study of women with GDM, but without medical conditions, who had a singleton, cephalic birth at 38-41 completed weeks gestation, in New South Wales, Australia between January 2010 and December 2016. Women who underwent IOL at 38, 39, 40 weeks gestation (38-, 39-, 40-induction groups) were compared with those who were managed expectantly and gave birth at and/or beyond the respective gestational age group (38-, 39-, 40-expectant groups). Multivariable logistic regression analysis was used to assess the association between IOL and adverse maternal birth and neonatal outcomes taking into account potential confounding by maternal age, country of birth, smoking, residential location, residential area of socioeconomic disadvantage and birth year. RESULTS: Of 676 762 women who gave birth during the study period, 66 606 (10%) had GDM; of these, 34799 met the inclusion criteria. Compared with expectant management, those in 38- (adjusted odds ratio (aOR) 1.11; 95% CI, 1.04-1.18), 39- (aOR 1.21; 95% CI, 1.14-1.28) and 40- (aOR 1.50; 95% CI, 1.40-1.60) induction groups had increased risk of caesarean section. Women in the 38-induction group also had an increased risk of composite neonatal morbidity (aOR 1.10; 95% CI, 1.01-1.21), which was not observed at 39- and 40-induction groups. We found no difference between groups in perinatal death or neonatal intensive care unit admission for births at any gestational age. CONCLUSION: In women with GDM but without specific medical conditions and eligible for vaginal birth, IOL at 38, 39, 40 weeks gestation is associated with an increased risk of caesarean section.

Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia.

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are the leading causes of maternal and fetal morbidity/mortality. The central deficit in both conditions is impaired placentation due to poor trophoblast invasion, resulting in a hypoxic milieu in which oxidative stress contributes to the pathology. We examine the factors driving the hypoxic response in severely preterm PE (n = 19) and IUGR (n = 16) placentae compared to the spontaneous preterm (SPT) controls (n = 13) using immunoblotting, RT-PCR, immunohistochemistry, proximity ligation assays, and Co-IP. Both hypoxia-inducible factor (HIF)-1α and HIF-2α are increased at the protein level and functional in pathological placentae, as target genes prolyl hydroxylase domain (PHD)2, PHD3, and soluble fms-like tyrosine kinase-1 (sFlt-1) are increased. Accumulation of HIF-α-subunits occurs in the presence of accessory molecules required for their degradation (PHD1, PHD2, and PHD3 and the E3 ligase von Hippel-Lindau (VHL)), which were equally expressed or elevated in the placental lysates of PE and IUGR. However, complex formation between VHL and HIF-α-subunits is defective. This is associated with enhanced VHL/DJ1 complex formation in both PE and IUGR. In conclusion, we establish a significant mechanism driving the maladaptive responses to hypoxia in the placentae from severe PE and IUGR, which is central to the pathogenesis of both diseases.

NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast.

Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) transcripts are elevated in the circulation of individuals whose pregnancies are complicated by preterm fetal growth restriction (FGR). In this paper, we show that the cases with preeclampsia (PE) have increased circulating NR4A2 transcripts compared to those with normotensive FGR. We aimed to establish whether the dysfunctional placenta mirrors the increase in NR4A2 transcripts and further, to uncover the function of placental NR4A2. NR4A2 expression was detected in preterm and term placental tissue; expressed higher at term. NR4A2 mRNA expression and protein were not altered in placentas from preterm FGR or PE pregnancies. Hypoxia (1% O2 compared to 8% O2) significantly reduced cytotrophoblast NR4A2 mRNA expression, but not placental explant NR4A2 expression. Silencing cytotrophoblast NR4A2 expression under hypoxia (via short interfering (si)RNAs) did not alter angiogenic Placental Growth Factor, nor anti-angiogenic sFlt-1 mRNA expression or protein secretion, but increased expression of cellular antioxidant, oxidative stress, inflammatory, and growth genes. NR4A2 expression was also not altered in a model of tumour necrosis factor-α-induced endothelial dysfunction, or with pravastatin treatment. Further studies are required to identify the origin of the circulating transcripts in pathological pregnancies, and investigate the function of placental NR4A2.

Factors Associated with Asthma Exacerbations During Pregnancy.

BACKGROUND: Asthma exacerbations during pregnancy are associated with adverse pregnancy outcomes. OBJECTIVE: The aim of this study was to establish factors associated with asthma exacerbations during pregnancy. METHODS: We obtained data from three cohorts of pregnant women with asthma recruited in eastern Australia (2004-2019; n = 1461). Severe exacerbations were defined as episodes of asthma requiring hospitalization, an emergency department visit, or prescription of oral corticosteroids after enrollment. Baseline information on potential risk factors included demographic characteristics, asthma characteristics (eg, lung function, asthma triggers, asthma control, medication use), pregnancy factors (eg, fetal sex, parity, antenatal care type), and other maternal factors (body mass index, smoking status, mental health). Backward stepwise logistic regression and Akaike information criterion were used to determine the best-fitting model. RESULTS: A total of 135 participants experienced a severe exacerbation during pregnancy (9.2%). Medium to high ICS dose was most strongly associated with severe asthma exacerbations (adjusted odds ratio = 3.20; 95% confidence interval, 1.85-5.53). Worse asthma control, possession of a written action plan, and a history of asthma exacerbations in the year preceding pregnancy were associated with an increased rate of exacerbations. CONCLUSIONS: Asthma exacerbations before pregnancy and more severe asthma at the beginning of pregnancy were associated with an increased rate of exacerbations during pregnancy. Despite Global Initiative for Asthma step 3 and 4 treatment and optimal management including a written asthma action plan, there is still a significant asthma burden in a group of women at high risk for severe exacerbations in pregnancy.

LOX-1 expression is reduced in placenta from pregnancies complicated by preeclampsia and in hypoxic cytotrophoblast.

OBJECTIVES: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is upregulated in the maternal vasculature in preeclampsia, and contributes to oxidative stress and endothelial dysfunction. However, its function in the placenta is unclear. This paper investigated LOX-1 expression in models of placental dysfunction and preeclampsia, and whether candidate therapeutics for preeclampsia could alter its expression. STUDY DESIGN: Placentas were collected from preterm pregnancies and cases of preterm preeclampsia and fetal growth restriction. Blood was collected from participants whose pregnancies were complicated by preterm fetal growth restriction and/or preeclampsia. Primary cytotrophoblast and placental explant tissue were cultured under hypoxic (1% O2) or normoxic (8% O2) conditions. Cytotrophoblast were exposed to 10% preeclamptic or control serum. Cytotrophoblast and preeclamptic explant tissue were treated with 100 µM esomeprazole, lansoprazole or rabeprazole. MAIN OUTCOME MEASURES: LOX-1 expression was assessed in all samples via qPCR. RESULTS: LOX-1 expression was reduced in placentas from cases of preterm preeclampsia, but not fetal growth restriction, compared to controls. LOX-1 expression was reduced in cytotrophoblast under hypoxia, but not in explant tissue. Treatment with preeclamptic serum in vitro did not alter cytotrophoblast LOX-1 expression. Circulating LOX-1 mRNA was unaltered in patients with fetal growth restriction, preeclampsia, and fetal hypoxia, compared to controls. Treatment with esomeprazole or lansoprazole in vitro increased placental LOX-1 expression. CONCLUSIONS: LOX-1 expression is reduced in preeclamptic placentas and hypoxic cytotrophoblast. Esomeprazole and lansoprazole increase placental LOX-1 expression. These findings demonstrate a role for LOX-1 in the placenta, and improve our understanding of maternal adaptations in pregnancy complications.

Evaluation of an online education module designed to reduce stillbirth.

BACKGROUND: The Safer Baby Bundle (SBB) eLearning is an online education module that addresses practice gaps in stillbirth prevention in Australia. It provides healthcare professionals with evidence-based resources for: smoking cessation; fetal growth restriction; decreased fetal movements; maternal safe going-to-sleep position; and timing of birth for women with risk factors for stillbirth. AIMS: To determine whether participants' reported knowledge and confidence in providing care designed to reduce stillbirth changed following completion of the module. To assess the module's suitability and acceptability, and participants' reported likelihood to change practice. MATERIALS AND METHODS: In-built surveys undertaken pre- and post-eLearning module assessed participant knowledge and confidence, module suitability and acceptability, and likelihood of practice change using Likert items. Responses were dichotomised. Differences pre- and post-module were tested using McNemar's test and differences by profession were examined using descriptive statistics and Pearson's χ2 test. RESULTS: Between 15 October 2019 and 2 November 2020, 5223 participants across Australia were included. Most were midwives (82.0%), followed by student midwives (4.6%) and obstetricians (3.3%). Reported knowledge and confidence improved in all areas (P < 0.001). Post-module 96.7-98.9% 'agreed' they had a sound level of knowledge and confidence across all elements of the SBB. Over 95% of participants agreed that the module was helpful and relevant, well organised, and easy to access and use. Eighty-eight percent reported they were likely to change some aspect of their clinical practice. CONCLUSIONS: The SBB eLearning module is a valuable education program that is well-received and likely to result in improvements in practice.

DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia.

Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether circulating DAAM2 mRNA could detect FGR, and whether the DAAM2 gene, known to play roles in the Wnt signalling pathway is expressed in human placenta and associated with dysfunction and FGR. We performed linear regression analysis to calculate area under the ROC curve (AUC) for DAAM2 mRNA expression in the maternal circulation of pregnancies complicated by preterm FGR. DAAM2 mRNA expression was assessed across gestation by qPCR. DAAM2 protein and mRNA expression was assessed in preterm FGR placenta using western blot and qPCR. DAAM2 expression was assessed in term cytotrophoblasts and placental explant tissue cultured under hypoxic and normoxic conditions by qPCR. Small interfering RNAs were used to silence DAAM2 in term primary cytotrophoblasts. Expression of growth, apoptosis and oxidative stress genes were assessed by qPCR. Circulating DAAM2 mRNA was elevated in pregnancies complicated by preterm FGR [p < 0.0001, AUC = 0.83 (0.78-0.89)]. Placental DAAM2 mRNA was detectable across gestation, with highest expression at term. DAAM2 protein was increased in preterm FGR placentas but demonstrated no change in mRNA expression. DAAM2 mRNA expression was increased in cytotrophoblasts and placental explants under hypoxia. Silencing DAAM2 under hypoxia decreased expression of pro-survival gene, BCL2 and oxidative stress marker, NOX4, whilst increasing expression of antioxidant enzyme, HMOX-1. The increased DAAM2 associated with FGR and hypoxia implicates a potential role in placental dysfunction. Decreasing DAAM2 may have cytoprotective effects, but further research is required to elucidate its role in healthy and dysfunctional placentas.

Protocol for probiotic therapy vs placebo for preterm prelabour rupture of membranes to prolong pregnancy duration (Pro-PPROM) trial.

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common preterm birth antecedent. Preterm infants experience increased adverse newborn outcome risks. Infection is a risk factor for early birth in PPROM. Current management is antibiotic therapy, antenatal corticosteroids and to plan delivery at 37 weeks gestation. The microbiota and probiotics are potentially protective and may improve outcomes. AIMS: The primary aim is to evaluate whether oral probiotic therapy (Lactobacillus fermentum CECT5716) administered during PPROM between 24 and 34 weeks gestation prolongs pregnancy duration. The secondary aim is to evaluate maternal and neonatal outcomes. MATERIALS AND METHODS: This is a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial in Australia. The population will be women with a singleton pregnancy and PPROM less than 34 weeks gestation. The intervention will be an oral probiotic therapy compared with a placebo control. The primary outcome will be the proportion of women still pregnant at seven days following PPROM. One-to-one randomisation will occur within 24 h of PPROM. The trial is powered (80%, alpha = 0.05) to detect an absolute percentage increase in the primary outcome of 30%, (from expected rate of 20% up to 50%). DISCUSSION: This trial will provide evidence for the effectiveness of the probiotic in prolonging pregnancy duration. Findings will inform the feasibility of a larger trial to examine the effect of oral probiotics on clinically important maternal and neonatal outcomes in PPROM.

Factors Associated with Nonadherence to Inhaled Corticosteroids for Asthma During Pregnancy.

BACKGROUND: Nonadherence is common among pregnant women prescribed inhaled corticosteroids (ICS) for asthma and may have serious consequences for mother and baby. Factors associated with ICS nonadherence have not been determined in this population. OBJECTIVES: To determine factors associated with {1} nonadherence to ICS in early-mid pregnancy (cross-sectional) and {2} persistent nonadherence to ICS during pregnancy (longitudinal). METHODS: Data used come from 3 prospective studies (2004-2019) involving women with asthma recruited by 23 weeks' gestation (N = 1614). Demographics, asthma history, and current symptoms were assessed, and spirometry was performed at baseline and throughout pregnancy. Women self-reported current medication use and number of ICS doses missed in the past week. Nonadherence was defined as ≥20% of prescribed dosages missed in the past week (baseline) and on at least 2 occasions during follow-up (persistent). Factors associated with ICS nonadherence were examined using backward stepwise logistic regression. RESULTS: Of 610 (38%) women prescribed ICS at baseline, 236 (39%) were classified as nonadherent. Of 612 (38%) women prescribed ICS during at least 2 follow-up visits, 149 (24%) were classified as persistent nonadherent. Factors associated with nonadherence at baseline were current or ex-smoking, non-Caucasian/non-Indigenous ethnicity, adult diagnosis of asthma, and lower lung function. Factors associated with persistent nonadherence to ICS were lower maternal age, higher parity, and no prescribed ICS at baseline. CONCLUSION: Young multiparous non-Caucasian/non-Indigenous mothers are at increased risk of being nonadherent to ICS during pregnancy. Strategies to improve ICS nonadherence should address maternal smoking and target women who (re-)initiate ICS use in pregnancy.

Pregnancy outcomes for women with a history of stroke: A population-based record linkage study.

BACKGROUND: Little is known about the pregnancy outcomes of women who have had a stroke prior to a first pregnancy. AIM: To identify a cohort of primiparous women giving birth to a single baby and compare the pregnancy outcomes of those with a pre-pregnancy stroke hospitalisation record to those without a stroke hospitalisation record. MATERIALS AND METHODS: Record linkage study of all primiparous women aged 15-44 years with singleton pregnancies birthing in New South Wales, Australia from 2003 to 2015. Stroke was identified from 2001 to 2015 hospital data using International Classification of Diseases tenth Edition - Australian Modification codes I60-64. Women whose first hospital record of stroke was during pregnancy or <42 days after birth were excluded. Outcomes included diabetes or hypertension during pregnancy, mode of delivery, haemorrhage, severe maternal morbidity (validated composite outcome indicator), gestational age at birth, Apgar score (1 min < 7), and small-for-gestational age. RESULTS: Of 487 767 women with a first pregnancy, 124 (2.5/10 000) had a hospital record which included a pre-pregnancy stroke diagnosis. Women with a stroke history were more likely to have an early-term delivery (37-38 weeks; relative risk (RR) 1.49, 95% CI 1.17-1.90) and a pre-labour caesarean (RR 2.83, 95% CI 2.20-3.63). There were no significant differences in other maternal or neonatal outcomes. CONCLUSION: This is the largest reported study of pregnancy and birth outcomes for women with a history of stroke. With the exception of pre-labour caesarean, there were no differences in pregnancy outcomes for women with a history of stroke compared with women with no history of stroke.

Stillbirth in Australia 2: Working together to reduce stillbirth in Australia: The Safer Baby Bundle initiative.

The rate of late gestation stillbirth in Australia is unacceptably high. Up to one third of stillbirths are preventable, particularly beyond 28 weeks' gestation. The aim of this second paper in the Stillbirth in Australia series is to highlight one key national initiative, the Safer Baby Bundle (SBB), which has been led by the Centre of Research Excellence in Stillbirth in partnership with state health departments. Addressing commonly identified evidence practice gaps, the SBB contains five elements that, when implemented together, should result in better outcomes than if performed individually. This paper describes the development of the SBB, what the initiative aims to achieve, and progress to date. By collaborating with Departments of Health and other partners to amplify uptake of the SBB, we anticipate a reduction of at least 20% in Australia's stillbirth rate after 28 weeks' gestation is achievable.

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth.

BACKGROUND: Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. METHODS: We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth. RESULTS: In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts. CONCLUSIONS: Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.