Characteristics of preterm births during COVID-19 mitigation measures.

BACKGROUND: During the COVID-19 pandemic, mitigation measures were associated with a reduction in preterm birth rates; while not clearly proven, this observation has sparked significant interest. AIM: To understand the cause of this reduction by exploring the characteristics of preterm birth cohorts. MATERIAL AND METHODS: We performed a retrospective cohort study where we compared women who delivered preterm in three Melbourne maternity hospitals and conceived between November 2019 and February 2020 (mitigation measures-exposed cohort) to women who delivered preterm and conceived between November 2018 and February 2019 (non-exposed cohort). We compared maternal characteristics, pregnancy complications, antenatal interventions, intrapartum care, and indications for delivery. RESULTS: In the exposed cohort, 252/3129 women delivered preterm (8.1%), vs 298/3154 (9.4%) in the non-exposed cohort (odds ratio (OR) 0.84, 95% CI 0.70-1.00, P = 0.051). The baseline characteristic of two cohorts were comparable. Rates of spontaneous preterm labour (sPTL) without preterm pre-labour rupture of membranes (PPROM) were lower in the exposed cohort (13.1% vs 24.2%, OR 0.47, P = 0.001) while PPROM occurred more often (48.0% vs 35.6%, OR 1.67, P = 0.003). With a non-statistically significant prolongation of pregnancy in the cohort exposed to mitigation measures for both sPTL without PPROM (35.4 vs 34.9 weeks, P = 0.703) and PPROM (35.6 vs 34.9 weeks, P = 0.184). The rate of spontaneous labour after PPROM was higher in the exposed cohort compared to the non-exposed cohort (40.1% vs 24.1%, OR 2.09, P < 0.001). CONCLUSION: The reduction in preterm delivery during mitigation measures may have been driven by a reduction in spontaneous labour without PPROM, which seemed to result in more PPROM later in pregnancy.

Creatine and pregnancy outcomes: a prospective cohort study of creatine metabolism in low-risk pregnant females.

BACKGROUND: Physiological adaptations during pregnancy alter nutrient and energy metabolism. Creatine may be important for maintaining cellular energy homeostasis throughout pregnancy. However, the impact of pregnancy on endogenous and exogenous creatine availability has never been comprehensively explored. OBJECTIVES: To undertake a prospective cohort study and determine the physiological ranges of creatine and associated metabolites throughout human pregnancy. METHODS: Females with a singleton low-risk pregnancy were recruited at an Australian health service. Maternal blood and urine were collected at 5-time points from 10-36 weeks of gestation, and cord blood and placental samples were collected at birth. Creatine and associated amino acids and metabolites of creatine synthesis were analyzed. Dietary data were captured to determine effects of exogenous creatine intake. Associations between creatine metabolism and neonatal growth parameters were examined. RESULTS: Two hundred and eighty-two females were included. Maternal plasma creatine remained stable throughout pregnancy [ß: -0.003 µM; 95% confidence interval (CI): -0.07, 0.07; P = 0.94], though urinary creatine declined in late gestation (ß: 0.38 µM/mmol/L creatinine (CRN); 95% CI: -0.47, -0.29; P < 0.0001). Plasma guanidinoacetate (GAA; the precursor to creatine during endogenous synthesis) fell from 10-29 weeks of gestation before rising until birth (ß: -0.38 µM/mmol/L CRN; 95% CI: -0.47, -0.29; P < 0.0001). Urinary GAA followed an opposing pattern (ß: 2.52 µM/mmol/L CRN; 95% CI: 1.47, 3.58, P < 0.001). Animal protein intake was positively correlated with maternal plasma creatine until ∼32 weeks of gestation (ß: 0.07-0.18 µM; 95% CI: 0.006, 0.25; P ≤ 0.001). There were no links between creatine and neonatal growth, but increased urinary GAA in early pregnancy was associated with a slight reduction in head circumference at birth (ß: -0.01 cm; 95% CI: -0.02, -0.004; P = 0.003). CONCLUSIONS: Although maternal plasma creatine concentrations were highly conserved, creatine metabolism appears to adjust throughout pregnancy. An ability to maintain creatine concentrations through diet and shifts in endogenous synthesis may impact fetal growth. This trial was registered at [registry name] as ACTRN12618001558213.

Investigating Menstruation and Adverse Pregnancy Outcomes: Oxymoron or New Frontier? A Narrative Review.

Not discounting the important foetal or placental contribution, the endometrium is a key determinant of pregnancy outcomes. Given the inherently linked processes of menstruation, pregnancy and parturition with the endometrium, further understanding of menstruation will help to elucidate the maternal contribution to pregnancy. Endometrial health can be assessed via menstrual history and menstrual fluid, a cyclically shed, easily and non-invasively accessible biological sample that represents the distinct, heterogeneous composition of the endometrial environment. Menstrual fluid has been applied to the study of endometriosis, unexplained infertility and early pregnancy loss; however, it is yet to be examined regarding adverse pregnancy outcomes. These adverse outcomes, including preeclampsia, foetal growth restriction (FGR), spontaneous preterm birth and perinatal death (stillbirth and neonatal death), lay on a spectrum of severity and are often attributed to placental dysfunction. The source of this placental dysfunction is largely unknown and may be due to underlying endometrial abnormalities or endometrial interactions during placentation. We present existing evidence for the endometrial contribution to adverse pregnancy outcomes and propose that a more comprehensive understanding of menstruation can provide insight into the endometrial environment, offering great potential value as a diagnostic tool to assess pregnancy risk. As yet, this concept has hardly been explored.

Immediate and longer-term impacts of fetal surveillance education on workforce knowledge and cognitive skills.

Background: Following the development of the Royal Australian College of Obstetricians and Gynaecologists Intrapartum Fetal Surveillance Guideline in 2003, an education program was developed to support guideline implementation and clinical practice. It was intended that improved clinician knowledge, particularly of cardiotocography, would reduce rates of intrapartum fetal morbidity and mortality. The program contains a multiple-choice assessment, designed to assess fetal surveillance knowledge and the application of that knowledge. We used the results of this assessment over time to evaluate the impact of the education program on clinicians' fetal surveillance knowledge and interpretive skills, in the immediate and longer-term. Methods: We undertook a retrospective analysis of the assessment results for all participants in the Fetal Surveillance Education Program, between 2004 and 2018. Classical Test Theory and Rasch Item Response Theory analysis were used to evaluate the statistical reliability and quality of the assessment, and the measurement invariance or stability of the assessments over time. Clinicians' assessment scores were then reviewed by craft group and previous exposure to the program. Results: The results from 64,430, broadly similar assessments, showed that participation in the education program was associated with an immediate improvement in clinician performance in the assessment. Performance improvement was sustained for up to 18 months following participation in the program and recurrent participation was associated with progressive improvements. These trends were observed for all craft groups (consultant obstetricians, doctors in training, general practitioners, midwives, student midwives). Conclusions: These findings suggest that the Fetal Surveillance Education Program has improved clinician knowledge and the associated cognitive skills over time. The stable difficulty of the assessment tool means any improvement in clinician's results, with ongoing exposure to the program, can be reliably assessed and demonstrated. Importantly this holds true for all craft groups involved in intrapartum care and the interpretation of cardiotocography.

Feasibility of a pregnancy intervention mimicking viral transmission mitigation measures on the incidence of preterm birth in high-risk pregnant women enrolled in antenatal clinics in Melbourne, Australia: protocol for a pilot, randomised trial.

INTRODUCTION: Preterm birth is a leading cause of perinatal morbidity and mortality. During the COVID-19 pandemic, reduction in rates of preterm birth in women exposed to viral mitigation measures was reported by multiple studies. In addition, others and we observed a more pronounced reduction of preterm birth in women who had previously experienced a preterm birth. The aim of this pilot study is to establish the feasibility of a lifestyle intervention based on viral mitigation measures in high-risk pregnancies, with the ultimate aim to reduce the incidence of preterm birth. METHODS AND ANALYSIS: One hundred pregnant women, enrolled in antenatal clinics at two tertiary maternity centres in Melbourne, Australia, who have had a previous preterm birth between 22 and 34 weeks gestation will be recruited. This is a two-arm, parallel group, open-label randomised controlled feasibility trial: 50 women will be randomised to the intervention group, where they will be requested to comply with a set of lifestyle changes (similar to the viral mitigation measures observed during the pandemic). Another 50 women will be randomised to the control group, where they will undergo standard pregnancy care. The primary outcome of this trial is feasibility, which will be assessed by measuring patient eligibility rate, recruitment rate, compliance rate and data completion rate. Secondary outcomes include incidence of preterm birth, maternal satisfaction, maternal quality of life and other pregnancy outcomes. Standard methods in statistical analysis for randomised controlled trials on an intention to treat basis will be followed. ETHICS AND DISSEMINATION: This trial has been approved by the Monash Human Research Ethics Committee; approval reference number RES-22-0000-122A. Study findings will be reported and submitted to peer-reviewed journals for publication, and presentation at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000753752; Pre-results.