The impact of the COVID-19 pandemic on antenatal care provision and associated mental health, obstetric and neonatal outcomes.

OBJECTIVES: The COVID-19 pandemic imposed many challenges on pregnant women, including rapid changes to antenatal care aimed at reducing the societal spread of the virus. This study aimed to assess how the pandemic affected perinatal mental health and other pregnancy and neonatal outcomes in a tertiary unit in Queensland, Australia. METHODS: This was a retrospective cohort study of pregnant women booked for care between March 2019 - June 2019 and March 2020 - June 2020. A total of 1984 women were included with no confirmed cases of COVID-19. The primary outcome of this study was adverse maternal mental health defined as an Edinburgh Postnatal Depression Scale score of ≥13 or an affirmative response to 'EPDS Question 10'. Secondary outcomes were preterm birth <37 weeks and <32 weeks, mode of birth, low birth weight, malpresentation in labour, hypertensive disease, anaemia, iron/vitamin B12 deficiency, stillbirth and a composite of neonatal morbidity and mortality. RESULTS: There were no differences in the primary perinatal mental health outcomes. The rates of composite adverse neonatal outcomes (27 vs. 34 %, p<0.001) during the pandemic were higher; however, there was no difference in perinatal mortality (p=1.0), preterm birth (p=0.44) or mode of delivery (p=0.38). CONCLUSIONS: Although there were no adverse consequences on maternal mental health during the pandemic, there was a concerning increase in neonatal morbidity potentially due to the altered model of maternity care implemented in the early COVID-19 pandemic.

Late termination of pregnancy at a major Queensland tertiary hospital, 2010-2020.

OBJECTIVE: To review rates of and indications for late pregnancy feticide at a major Queensland tertiary perinatal centre over the past decade. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: The Centre for Advanced Prenatal Care at the Royal Brisbane and Women's Hospital, a tertiary perinatal centre; feticides of singleton pregnancies of at least 22 weeks' gestation, 1 January 2010 - 31 December 2020. MAIN OUTCOME MEASURES: Indications for feticide; median gestational age at feticide; referral source; time between referral, maternal-fetal medicine review, and feticide. RESULTS: During 2010-2020, 305 feticides were undertaken at 22 weeks' gestation or later. The annual number of feticides increased from 20 in 2010 to 54 in 2020. The median gestational age at feticide was consistent across the decade (24+6 weeks; range, 17+0 to 37+1 weeks). The most frequent fetal indications for feticide were neurological abnormalities (110 of 305, 36%), aneuploidy or genetic syndromes (67, 22%), and cardiac malformations (59, 19%). Most women were seen for review within seven days of referral for feticide (154 of 197 for whom this information was available, 78%; median, five days; range, 0-34 days), and 136 of 197 feticides (69%) were undertaken within seven days of the initial maternal-fetal medicine review. CONCLUSIONS: Most late pregnancy feticides were performed because of fetal indications, primarily structural malformations or genetic abnormalities. Despite advances in prenatal imaging and diagnosis, late termination of pregnancy remains a necessary option in some pregnancies with maternal or fetal indications, and equitable access to late termination of pregnancy services is a vital component of reproductive health care.

The association between induction of labour in nulliparous women at term and subsequent spontaneous preterm birth: a retrospective cohort study.

OBJECTIVES: To evaluate the rate of subsequent spontaneous preterm birth in patients with previous induction of labour at term compared to women with previous spontaneous labour at term. METHODS: This was a retrospective cohort study of all women with consecutive births at the Royal Brisbane and Women's Hospital between 2014 and 2018. All nulliparous women with a singleton pregnancy and induction of labour at term or in spontaneous labour at term in the index pregnancy were included. Data was extracted from electronic medical records. The outcome of spontaneous preterm birth in the subsequent pregnancy was compared between patients with previous term induction of labour and in previous term spontaneous labour. RESULTS: A total of 907 patients with consecutive births met the inclusion criteria; of which 269 (29.7%) had a term induction of labour and 638 (70.3%) had a term spontaneous labour in the index pregnancy. The overall subsequent spontaneous preterm birth rate was 2.3%. Nulliparous women who underwent term induction of labour were less likely to have a subsequent preterm birth compared to nulliparous women in term spontaneous labour (0.74 vs. 2.98%; odds ratio [OR], 0.25; 95% confidence interval, 0.06-1.07; p=0.0496) in the index pregnancy. This however was not significant once adjusted for confounders (adjusted OR, 0.29; p=0.10). Spontaneous preterm birth was associated with a previous spontaneous labour compared to induction of labour between 37 to 37+6 and 38 to 38+6 weeks (adjusted OR 0.18 and 0.21; p=0.02 and 0.004 respectively). CONCLUSIONS: Term induction of labour does not increase the risk of subsequent spontaneous preterm birth compared to spontaneous labour at term in nulliparous women. Further research is needed to validate these findings in a larger cohort of women and to evaluate the effect of elective IOL among low-risk nulliparous women.

Making every birth count: Outcomes of a perinatal mortality audit program.

BACKGROUND: Stillbirth rates have shown little improvement for two decades in Australia. Perinatal mortality audit is key to prevention, but the literature suggests that implementation is suboptimal. AIM: To determine the proportion of perinatal deaths which are associated with contributing factors relating to care in Queensland, Australia. MATERIALS AND METHODS: Retrospective audit of perinatal deaths ≥ 34 weeks gestation by the Health Department in Queensland was undertaken. Cases and demographic information were obtained from the Queensland Perinatal Data Collection. A multidisciplinary panel used the Perinatal Society of Australia and New Zealand (PSANZ) perinatal mortality audit guidelines to classify the cause of death and to identify contributing factors. Contributing factors were classified as 'insignificant', 'possible', or 'significant'. RESULTS: From 1 January to 31 December 2018, 65 deaths (56 stillbirths and nine neonatal deaths) were eligible and audited. Most deaths were classified as unexplained (51.8% of stillbirths). Contributing factors were identified in 46 (71%) deaths: six insignificant (all stillbirths), 20 possibly related to outcome (17 stillbirths), and 20 significantly (16 stillbirths). Areas for practice improvements mainly related to the care for women with risk factors for stillbirth, especially antenatal care. The PSANZ guidelines were applied and enabled a systematic approach. CONCLUSIONS: A high proportion of late gestation perinatal deaths are associated with contributing factors relating to care. Improving antenatal care for women with risk factors for stillbirth is a priority. Perinatal mortality audit is a valuable step in stillbirth prevention and the PSANZ guidelines allow a systematic approach to aid implementation and reporting.

Prediction of time of delivery using cervical length measurement in women with threatened preterm labor.

OBJECTIVE: To evaluate the use of transvaginal (TV) sonographic cervical length (CL) measurement alone in predicting time of delivery in women who present in threatened preterm labor. METHODS: A retrospective cohort study at Royal Brisbane and Women's Hospital of all women who presented between 22 weeks and 0 days and 35 weeks and six-day gestation in threatened preterm labor and were admitted for ongoing management including a TV sonographic CL measure. The accuracy of CL for predicting time of delivery was compared between women with a short cervix (CL < 25 mm) and those with a normal cervix (CL ≥25 mm). The predictive accuracy of CL for spontaneous preterm delivery was analyzed with different outcome-specific thresholds. RESULTS: One hundred and forty-six women with threatened preterm labor met the inclusion criteria; of which 74 (50.7%) had a short cervix and 72 (49.3%) had a normal cervix. The group with short cervix were more likely to deliver prematurely before 37-week gestation, as well as a shorter time interval between initial presentation and delivery and delivery within 14 days from presentation (p = .0002, p = .0001, and p = .0001, respectively). Similarly, with respect to the area under the receiver operator characteristic curves, CL measurement was found to be significant for time of delivery before or after 37 weeks (p < .0001), preterm delivery before 34 (p = .0003) and 31 (p < .0001) weeks; and preterm delivery within 14 days from presentation (p < .0001). Cervical length measurement has a high negative predictive value ranging from 94.9 to 97.1% depending on the different CL threshold used. CONCLUSIONS: Cervical length measurement at the time of presentation was significantly associated with the risk of preterm delivery in women presenting with threatened preterm labor and a short cervix. Cervical length measurement was also helpful in predicting time of delivery within 14 days from presentation. The negative predictive value and predictive accuracy of CL as a single measure were of significance.

The risk of preterm delivery and pregnancy outcomes in women with asymptomatic short cervix: a retrospective cohort study.

OBJECTIVE: Routine cervical length measurement in asymptomatic pregnant women to prevent preterm birth has not been universally adopted due to poor predictive accuracy. The purpose of our study was to evaluate the risk of preterm delivery and pregnancy outcomes in women with asymptomatic short cervix and examine the implications of gestational age at presentation on these outcomes. STUDY DESIGN: This was a retrospective cohort study of women with singleton pregnancies who presented prior to or at 32 + 0 weeks with an asymptomatic short cervix (≤25 mm) between April 2014 to March 2018 at a single tertiary maternity center. Women with cervical length ≤25 mm were grouped into four cohorts according to gestational age at presentation: Obstetric outcomes were compared between the cohorts and the general cohort of women delivering during the same period. Outcomes were compared using Mann-Whitney U, chi-square tests, and logistic regression. Survival analysis was carried out to compare the probability of delivery for each subgroup. RESULTS: The rate of spontaneous preterm birth <37 weeks was highest in the cohort presenting at 25 + 0-27 + 6 weeks, and lowest in the first cohort presenting at <22 + 0 (60.0 versus 22.2%, p < .05). When compared with the general cohort, the rate of spontaneous preterm birth at <37-week gestation was significantly higher in the asymptomatic short cervix cohort (40.4 versus 8.7%, p < .001), with a 7.1-fold increase in the relative risk of spontaneous PTB. CONCLUSIONS: In asymptomatic women, cervical shortening showed significant increase in the risk of preterm birth. Our study findings suggest that routine cervical screening may be helpful in predicting risk of preterm birth even in women who are considered low-risk for preterm birth.

Does the length of second stage of labour or second stage caesarean section in nulliparous women increase the risk of preterm birth in subsequent pregnancies?

OBJECTIVES: This study aimed to investigate the role of prolonged second stage of labour and second stage caesarean section on the risk of spontaneous preterm birth (sPTB) in a subsequent pregnancy. METHODS: This was a retrospective cohort study of nulliparous women with two consecutive singleton deliveries between 2014 and 2017 at a tertiary centre. In the vaginal delivery cohort, subsequent pregnancy outcomes for women with a prolonged second stage (>2 h) were compared with those with a normal second stage (≤2 h). In the caesarean delivery cohort, women with a first stage or a second stage were compared with the vaginal delivery cohort. The primary outcome was subsequent sPTB. RESULTS: A total of 821 women met inclusion criteria, of which 74.8% (614/821) delivered vaginally and 25.2% (207/821) delivered by caesarean section. There was no association between a prolonged second stage in the index pregnancy and subsequent sPTB (aOR 0.70, 95% CI 0.13-3.83, p=0.7). The risk of subsequent sPTB was threefold for those with a second stage caesarean section; however this did not reach statistical significance. CONCLUSIONS: A prolonged second stage of labour in the index pregnancy is not associated with an increased risk of subsequent sPTB. A second stage caesarean section in the index pregnancy may be associated with an increased risk of subsequent sPTB, however there was no statistically significant difference. These findings are important for counseling and suggest that the effects of these factors are not clinically significant to justify additional interventions in the subsequent pregnancy.

Hadronic Light-by-Light Scattering Contribution to the Muon Anomalous Magnetic Moment from Lattice QCD.

We report the first result for the hadronic light-by-light scattering contribution to the muon anomalous magnetic moment with all errors systematically controlled. Several ensembles using 2+1 flavors of physical mass Möbius domain-wall fermions, generated by the RBC and UKQCD collaborations, are employed to take the continuum and infinite volume limits of finite volume lattice QED+QCD. We find a_{µ}^{HLbL}=7.87(3.06)_{stat}(1.77)_{sys}×10^{-10}. Our value is consistent with previous model results and leaves little room for this notoriously difficult hadronic contribution to explain the difference between the standard model and the BNL experiment.

The efficacy of quantitative fetal fibronectin in predicting spontaneous preterm birth in symptomatic women: A retrospective cohort study.

BACKGROUND: Recent data suggest that quantitative measurements of fetal fibronectin can be used accurately to predict increased risk of preterm birth. AIM: The purpose of this study was to demonstrate that the quantification of fetal fibronectin improves diagnostic accuracy in women who present with symptoms suggestive of threatened preterm labour (TPL) using a quantitative fetal fibronectin (qfFN) bedside analyser. STUDY DESIGN: This was a retrospective cohort study of pregnant women who presented between 22+6 and 32+6  weeks gestation with symptoms of TPL who had qfFN measured using the Rapid fFN Q10 system. The ability to predict spontaneous preterm birth (sPTB) within 48 h, 14 days and <34 weeks gestation at qfFN thresholds of 10, 50 and 200 ng/mL was assessed. RESULTS: The overall rate of sPTB <34 weeks was 4.1% (n = 373). For deliveries within 48 h, within 14 days and <34 weeks, a qfFN threshold of 200 ng/mL had positive predictive values of 26.7%, 42.9% and 46.7%, respectively, when compared to patients with qfFN values of 0-9 ng/mL. The corresponding relative risks were 68.5, 53.8 and 38.0, respectively CONCLUSION: Quantitative fetal fibronectin testing with thresholds of 10, 50 and 200 ng/mL allows for more accurate prediction of preterm birth in symptomatic women. This higher degree of discrimination allows for more directed interventions for high-risk patients and reduces the cost and burden of unnecessary treatment for low-risk patients.

The feasibility of a clinical audit tool to investigate stillbirth in Australia - a single centre experience.

BACKGROUND: The stillbirth rate in Australia is 7 per 1000 births (Australia's Mothers and Babies 2014-in brief. Perinatal Statistics Series no. 32. Cat no. PER 87, Canberra, AIHW, 2016). The Perinatal Society of Australia and New Zealand (PSANZ) developed guidelines to standardise the investigations into stillbirth. AIMS: To identify causes of stillbirths and stillbirth care using the National Perinatal Death Clinical Audit Tool (National Perinatal Death Clinical Audit Tool, Australian and New Zealand Stillbirth Alliance [ANZSA]/Perinatal Society of Australia and New Zealand [PSANZ]) and compare it to the PSANZ recommendations. Documentation of examination findings and follow-up after stillbirth were also reviewed. MATERIALS AND METHODS: From the total of 515 registered stillbirths at a Queensland hospital, 170 stillbirths were considered unexplained after chart review between July 2004 and September 2014. The National Perinatal Death Clinical Audit Tool was applied and resulting underlying causes of stillbirths were classified using the PSANZ perinatal mortality classification system. RESULTS: The stillbirth rate for this centre was 11.2 per 1000 births. A cause of fetal death was established in 55.4% (93/168) and 75 cases (44.6%) remained unexplained corresponding to 14.6% of all registered stillbirths (75/515). Over half of the women (52.7%) were nulliparous. High rates of autopsy (47.3%), bereavement support (99.4%) and placental histopathology (98.8%) were noted. The general practitioner was notified in 98.7% of cases at the time of stillbirth; 34.1% of babies were small for gestational age at birth, 18.9% were growth-restricted at birth and 21.4% of women were current smokers. CONCLUSION: The National Perinatal Death Clinical Audit Tool facilitates and streamlines stillbirth investigations and thus helps to identify underlying causes of stillbirth.

Novel |V_{us}| Determination Using Inclusive Strange τ Decay and Lattice Hadronic Vacuum Polarization Functions.

We propose and apply a new approach to determining |V_{us}| using dispersion relations with weight functions having poles at Euclidean (spacelike) momentum which relate strange hadronic τ decay distributions to hadronic vacuum polarization (HVP) functions obtained from lattice quantum chromodynamics. We show examples where spectral integral contributions from the region where experimental data have large errors or do not exist are strongly suppressed but accurate determinations of the relevant lattice HVP combinations remain possible. The resulting |V_{us}| agrees well with determinations from K physics and three-family Cabibbo-Kobayashi-Maskawa unitarity. Advantages of this new approach over the conventional hadronic τ decay determination employing flavor-breaking sum rules are also discussed.

Connected and Leading Disconnected Hadronic Light-by-Light Contribution to the Muon Anomalous Magnetic Moment with a Physical Pion Mass.

We report a lattice QCD calculation of the hadronic light-by-light contribution to the muon anomalous magnetic moment at a physical pion mass. The calculation includes the connected diagrams and the leading, quark-line-disconnected diagrams. We incorporate algorithmic improvements developed in our previous work. The calculation was performed on the 48^{3}×96 ensemble generated with a physical pion mass and a 5.5 fm spatial extent by the RBC and UKQCD Collaborations using the chiral, domain wall fermion formulation. We find a_{µ}^{HLbL}=5.35(1.35)×10^{-10}, where the error is statistical only. The finite-volume and finite lattice-spacing errors could be quite large and are the subject of ongoing research. The omitted disconnected graphs, while expected to give a correction of order 10%, also need to be computed.

Mechanics in the Querelle des Anciens et des Modernes.

The debate about the superiority of ancient versus modern culture, known as the Querelle des anciens et des modernes, also found expression in conflicting positions about the developing mathematical methods of natural philosophy. Isaac Newton explicitly referred to the authority of Euclidean geometry as a justification for the conservative form of the proofs in his Principia Mathematica, where he avoided the use of analytic geometry and infinitesimal calculus, the central innovations of seventeenth-century mathematics, as much as possible. Rather, he modeled his proofs, just like the overall structure of the treatise, as closely as possible on Euclid's geometry. A century later, however, Joseph-Louis Lagrange announced in the introduction to his Mechanique Analytique that no geometrical diagrams would be found there and that Newtonian mechanics was presented exclusively in the form of analytic equations. This essay analyzes the relationship of this radical change in the theoretical methodology of mechanics to the actors' ideas about ancient science and its authority. It also discusses the consequent development of a conception of ancient science as distinct from modern science and the relation of this conception to a history of science in our contemporary sense.

Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure.

BACKGROUND: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-alpha and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 initiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. METHODS: Fifty patients with CHF (aged 66.9+/-12.6 years, mean ejection fraction 22.1+/-9.2%, NYHA II-IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5+/-9.8 years) were examined. Thirty-two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry. RESULTS: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P<0.001; P-selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P<0.001). CD154 expression on platelets positively correlated with increasing NYHA-class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet-therapy with aspirin did not influence CD154 or P-selectin expression on platelets. CONCLUSION: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40-CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.

Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure.

Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Many studies have shown enhanced plasma levels of proinflammatory cytokines [i.e. tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6] in patients with CHF. However, there are only few reports on the regulation of anti-inflammatory cytokines such as IL-10. IL-10 has potent deactivating properties in macrophages and T-cells and thus acts as a down-regulator of cell-mediated immune responses. The aim of the present study was to assess whether serum concentrations of IL-10 significantly differ between patients with CHF and healthy control subjects. Patients with CHF [ n =50; 66.9+/-12.6 years; mean ejection fraction, 22.1+/-9.2%; New York Heart Association (NYHA) class II-IV] and 25 healthy controls (63.6+/-10.2 years) were examined. Of the 50 patients with CHF, 32 patients were taking aspirin (100 mg/day) and 33 patients had lipid-lowering therapy with a statin. Serum IL-10 as well as TNF-alpha concentrations were measured using commercially available immunoassays. Patients with CHF showed significantly lower IL-10 concentrations (2.3+/-1.9 compared with 5.2+/-2.3 pg/ml; P <0.001). Patients with advanced CHF (NYHA class III and IV) had the lowest IL-10 plasma levels. Aspirin and statin therapy did not significantly influence serum levels of IL-10. The ratio of TNF-alpha to IL-10 was significantly higher in patients with advanced CHF (NYHA class III and IV, ratio 3.2+/-1.2 and 3.1+/-1.1 respectively, compared with control 0.4+/-0.2; P <0.01). Our present study demonstrates significantly decreased serum levels of IL-10 in patients with advanced CHF. Since IL-10 is known as a potent anti-inflammatory cytokine, its decrease in advanced CHF may favour the inflammatory milieu in CHF.