Reduction in spontaneous and iatrogenic preterm births in twin pregnancies during COVID-19 lockdown in Melbourne, Australia: a multicenter cohort study.

BACKGROUND: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. METHODS: Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. Multivariable log-binomial regression models were used to compare perinatal outcomes between a pre-pandemic group to women in whom weeks 20+0 to 40+0 of gestation occurred entirely during one of two lockdown-exposure periods: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. RESULTS: Total preterm births < 37 weeks were significantly lower in exposure 1 compared with the pre-pandemic period (63.1% vs 68.3%; adjusted risk ratio 0.92 95% CI 0.87-0.98, p = 0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3%; adjusted risk ratio 0.95 95% CI 0.90-0.99, p = 0.04). There were also lower rates of preterm birth < 34 weeks (19.9% vs 23.0%, adjusted risk ratio 0.93 95% CI 0.89-0.98 p = 0.01) and total iatrogenic births for fetal compromise (13.4% vs 20.4%; adjusted risk ratio 0.94 95% CI 0.89-0.98, p = 0.01). There were fewer special care nursery admissions (38.5% vs 43.4%; adjusted risk ratio 0.91 95% CI 0.87-0.95, p < 0.001) but no significant changes in stillbirth (1.5% vs 1.6%; adjusted risk ratio 1.00 95% CI 0.99-1.01, p = 0.82). Compared with the pre-pandemic period, there were more preterm births < 28 weeks and neonatal intensive care unit admissions in exposure 2. CONCLUSIONS: Melbourne's first lockdown-exposure period was associated with lower preterm births in twins without significant differences in adverse newborn outcomes. Our findings provide insights into the influences on preterm birth and the optimal timing of delivery for twins.

Reductions in stillbirths and preterm birth in COVID-19-vaccinated women: a multicenter cohort study of vaccination uptake and perinatal outcomes.

BACKGROUND: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. OBJECTIVE: This study aimed to measure the rate of COVID-19 vaccine uptake among women giving birth in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. STUDY DESIGN: This was a retrospective multicenter cohort study conducted after the June 2021 government recommendations for messenger RNA COVID-19 vaccination during pregnancy. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births at ≥20 weeks' gestation from July 1, 2021 to March 31, 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20 to 43 of gestation fell entirely within the 9-month data collection period. The primary outcomes were the rates of stillbirth and preterm birth (spontaneous and iatrogenic) in singleton pregnancies of at least 24 weeks' gestation, after exclusion of congenital anomalies. Secondary perinatal outcomes included the rate of congenital anomalies among infants born at ≥20 weeks' gestation and birthweight ≤third centile and newborn intensive care unit admissions among infants born without congenital anomalies at ≥24 weeks' gestation. We calculated the adjusted odds ratio of perinatal outcomes among vaccinated vs unvaccinated women using inverse propensity score-weighting regression adjustment with multiple covariates; P<.05 was considered statistically significant. RESULTS: Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were more likely to be older, nulliparous, nonsmoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth. Vaccinated women had a significantly lower rate of stillbirth compared with unvaccinated women (0.2% vs 0.8%; adjusted odds ratio, 0.18; 95% confidence interval, 0.09-0.37; P<.001). Vaccination was associated with a significant reduction in total preterm births at <37 weeks (5.1% vs 9.2%; adjusted odds ratio, 0.60; 95% confidence interval, 0.51-0.71; P<.001), spontaneous preterm birth (2.4% vs 4.0%; adjusted odds ratio, 0.73; 95% confidence interval, 0.56-0.96; P=.02), and iatrogenic preterm birth (2.7% vs 5.2%; adjusted odds ratio, 0.52; 95% confidence interval, 0.41-0.65; P<.001). Infants born to vaccinated mothers also had lower rates of admission to the neonatal intensive care unit. There was no significant increase in the rate of congenital anomalies or birthweight ≤3rd centile in vaccinated women. Vaccinated women were significantly less likely to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%; adjusted odds ratio, 0.72; 95% confidence interval, 0.56-0.94; P=.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks' gestation. CONCLUSION: COVID-19 vaccination during pregnancy was associated with a reduction in stillbirth and preterm birth, and not associated with any adverse impact on fetal growth or development. Vaccine coverage was substantially influenced by known social determinants of health.

Abnormal vaginal flora and spontaneous preterm birth in high-risk singleton pregnancies with cervical cerclage.

OBJECTIVE: To investigate abnormal vaginal and suture-based bacterial flora for associations with spontaneous preterm birth in high-risk singleton pregnancies with an ultrasound-indicated or emergency cervical cerclage. MATERIALS AND METHODS: A retrospective study of 196 singleton pregnancies with an ultrasound-indicated or emergency cerclage at the Royal Women's Hospital, Australia, from 2004 to 2018. High vaginal swabs were collected regularly between 14 and 26 weeks' gestation, including pre- and post-cerclage insertion, and sent for microscopy and culture. Cervical suture was cultured upon removal. Primary outcomes were spontaneous preterm birth <37, <34 and <30 weeks. RESULTS: 43.4% (85/196) of women delivered preterm. The acquisition and persistence of vaginal Escherichia coli following cerclage insertion were independently associated with spontaneous preterm birth <37 weeks (p = .0225, p = .0477). Escherichia coli growth from the cervical suture upon removal was associated with spontaneous preterm birth <34 weeks (p = .0458). The acquisition of vaginal mixed anaerobes post-cerclage was independently associated with spontaneous preterm birth <34 weeks (p = .0480). CONCLUSION: For singleton pregnancies with an ultrasound-indicated or emergency cerclage, the presence of vaginal or suture-based Escherichia coli following cerclage insertion yields increased risk of cerclage failure and spontaneous preterm birth.

Increase in preterm stillbirths in association with reduction in iatrogenic preterm births during COVID-19 lockdown in Australia: a multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women. OBJECTIVE: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. STUDY DESIGN: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates. RESULTS: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32). CONCLUSION: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.

Collaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia.

BACKGROUND: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. METHODS: Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births >20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random 'signals' in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. ETHICS AND DISSEMINATION: Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). TRIAL REGISTRATION NUMBER: ACTRN12620000878976; Pre-results.

The addition of fetal scalp blood lactate measurement as an adjunct to cardiotocography to reduce caesarean sections during labour: The Flamingo randomised controlled trial.

BACKGROUND: Fetal scalp blood sampling for lactate measurement (FBSLM) is sometimes used to assist in identification of the need for expedited birth in the presence of an abnormal cardiotocograph (CTG). However, there is no randomised controlled trial evidence to support this. AIM: To determine whether adding FBSLM reduces the risk of birth by emergency caesarean section in labours complicated by an abnormal CTG, compared with CTG without FBS. MATERIAL AND METHODS: Labouring women at a tertiary maternity hospital in Melbourne, Australia with a singleton, cephalic presentation, at ≥37 weeks gestation with an abnormal CTG pattern were randomised to the intervention (n = 61), with intermittent FBSLM in addition to CTG monitoring, or control (CTG without FBS, n = 62). The primary outcome was rate of birth by caesarean section. Secondary outcomes included overall operative birth and fetal and neonatal safety endpoints. TRIAL REGISTRATION: ACTRN12611000172909. RESULTS: The smaller than anticipated sample was unable to demonstrate an effect from adding FBSLM to CTG monitoring on birth by caesarean section vs monitoring by CTG without FBS (25/61 and 28/62 respectively, P = 0.64, risk ratio 0.91, 95% confidence intervals 0.60-1.36). One newborn infant in the CTG group met the criteria for the composite neonatal outcome of death or serious outcome, neonatal encephalopathy, five-minute Apgar score < 4, neonatal resuscitation, admission to neonatal intensive care unit for 96 h or more. CONCLUSION: We were unable to provide robust evidence of the effectiveness of FBSLM to improve the specificity of the CTG in the assessment of fetal wellbeing.

Preterm birth prediction in asymptomatic women at mid-gestation using a panel of novel protein biomarkers: the Prediction of PreTerm Labor (PPeTaL) study.

BACKGROUND: Accurate prediction of spontaneous preterm labor/preterm birth in asymptomatic women remains an elusive clinical challenge because of the multi-etiological nature of preterm birth. OBJECTIVE: The aim of this study was to develop and validate an immunoassay-based, multi-biomarker test to predict spontaneous preterm birth. MATERIALS AND METHODS: This was an observational cohort study of women delivering from December 2017 to February 2019 at 2 maternity hospitals in Melbourne, Australia. Cervicovaginal fluid samples were collected from asymptomatic women at gestational week 16+0-24+0, and biomarker concentrations were quantified by enzyme-linked immunosorbent assay. Women were assigned to a training cohort (n = 136) and a validation cohort (n = 150) based on chronological delivery dates. RESULTS: Seven candidate biomarkers representing key pathways in utero-cervical remodeling were discovered by high-throughput bioinformatic search, and their significance in both in vivo and in vitro studies was assessed. Using a combination of the biomarkers for the first 136 women allocated to the training cohort, we developed an algorithm to stratify term birth (n = 124) and spontaneous preterm birth (n = 12) samples with a sensitivity of 100% (95% confidence interval, 76-100%) and a specificity of 74% (95% confidence interval, 66-81%). The algorithm was further validated in a subsequent cohort of 150 women (n = 139 term birth and n = 11 preterm birth), achieving a sensitivity of 91% (95% confidence interval, 62-100%) and a specificity of 78% (95% confidence interval, 70-84%). CONCLUSION: We have identified a panel of biomarkers that yield clinically useful diagnostic values when combined in a multiplex algorithm. The early identification of asymptomatic women at risk for preterm birth would allow women to be triaged to specialist clinics for further assessment and appropriate preventive treatment.

Cervical length surveillance for predicting spontaneous preterm birth in women with uterine anomalies: A cohort study.

INTRODUCTION: Uterine anomalies occur in an estimated 5% of women and have been shown to confer a higher risk of spontaneous preterm birth (SPTB). A sonographically short cervix (<25 mm) is a risk indicator for SPTB, although its predictive utility has been little studied in this specific high-risk population. We aimed to assess the pregnancy outcomes and predictive ability of short cervix in a cohort of women with uterine anomalies attending a high-risk antenatal clinic. MATERIAL AND METHODS: This historical cohort study assessed all pregnancies in women with congenital uterine anomalies referred to the Preterm labor Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2013. Logistic and linear regressions and receiver-operator curves were used to examine associations between cervical length and preterm birth. RESULTS: SPTB (<37 weeks' gestation) occurred in 23% of the 86 pregnancies (n = 20); rates by subgroup were: unicornuate uterus 60% (n = 3/5), uterus didelphys 40% (n = 6/15), bicornuate uterus 18% (n = 9/51), septate uterus 13% (n = 2/15). Preterm prelabor rupture of membranes occurred in 55% of spontaneous preterm births and was not independently associated with the presence of cervical cerclage or ureaplasma urealyticum. Short cervical length was associated with SPTB in women with septate uterus. Short cervix at 24 weeks (not at 16 or 20 weeks) was moderately predictive of SPTB < 34 weeks. CONCLUSIONS: Women with uterine anomalies are at increased risk of spontaneous preterm birth, particularly those with unicornuate uterus or uterus didelphys, but cervical surveillance did not identify these cases. Short cervix may be associated with SPTB in women with septate uterus. Preterm prelabor rupture of membranes occurred in 55% of SPTB. More research is required into etiology to help determine appropriate monitoring and treatment.

Assessment of Placental Cortisol Pathway Gene Expression in Term Pregnant Women with Anxiety.

INTRODUCTION: The aim of this study was to expand on this field of work by examining, within a cohort of pregnant women with diagnosed clinical anxiety, the mRNA expression of a panel of genes associated with the cortisol pathway and comparing them to controls. METHODS: Placental samples were obtained from 24 pregnant women, 12 with a diagnosed anxiety disorder and 12 with no psychiatric history, within 30 min of delivery. Differential expression analysis of 85 genes known to be involved in glucocorticoid synthesis, metabolism or signalling was conducted for the: (1) full sample, (2) those at term without labour (5 cases, 7 controls) and (3) those at term with labour (7 cases, 5 controls). Correlation analyses between gene expression and measures of anxiety and depressive symptom severity were also conducted. RESULTS: No robust difference in placental gene expression between pregnant women with and without anxiety disorder was found nor did we detect robust differences by labour status. However, correlational analyses putatively showed a decrease in PER1 expression was associated with an increase in anxiety symptom severity, explaining up to 32% of the variance in anxiety symptom severity. DISCUSSION: Overall, the strongest correlation was found between a decrease in placental PER1 expression and increased anxiety scores. Labour status was found to have a profound effect on mRNA expression. The placental samples obtained from women following labour produced greater numbers of significant differences in mRNA species expression suggesting that in long-standing anxiety the placenta may respond differently under conditions of chronic stress.

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus.

BACKGROUND: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. AIM: To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. METHODS: Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. RESULTS: Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 µg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. CONCLUSION: Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.

Rescue Adjuvant Vaginal Progesterone May Improve Outcomes in Cervical Cerclage Failure.

Introduction Aim of the study was to evaluate the effect of rescue adjuvant vaginal progesterone in women with ongoing, transvaginal ultrasound (TVUS)-confirmed cervical shortening despite cervical cerclage. Materials and Methods A retrospective case control study was performed of women undergoing cervical surveillance following either history- or ultrasound-indicated cervical cerclage. We compared women managed with cervical cerclage and vaginal progesterone to women managed with cervical cerclage alone. Women with a singleton pregnancy who underwent cervical cerclage were identified from a database. Data on the concurrent use of vaginal progesterone, cervical length measurements, interventions and birth outcomes were collected from patient notes and clinical pathology notes. Patients from each intervention group were matched, based on exact shortest cervical length measurements obtained during surveillance and age of gestation when the measurement was obtained. Results 66 women were matched and included in the study, based on exact shortest cervical length measurements. Each group had an identical mean shortest cervical length of 12.09 mm. The outcomes of 33 women who received both cervical cerclage and vaginal progesterone were compared to the outcomes of 33 women who were treated with cervical cerclage alone. The administration of vaginal progesterone to women with ongoing cervical shortening despite cervical cerclage was found to significantly prolong the pregnancy (36.36 weeks vs. 32.63 weeks; p = 0.0036) compared to women treated with cerclage alone. This use of rescue adjuvant vaginal progesterone was also associated with higher birth weights (2829 g vs. 2134 g; p = 0.0065) compared to women who had cervical cerclage alone; however, there was no difference in Apgar scores, composite neonatal morbidity or neonatal intensive care admission. Conclusion Women with cervical shortening despite the presence of cervical cerclage may benefit from further TVUS cervical length surveillance and the administration of vaginal progesterone if further cervical shortening occurs. Despite both groups having clinically significant shortened cervical lengths and cervical cerclage in situ, adjunct vaginal progesterone treatment resulted in older gestational age at birth and higher birth weight. Further investigation and confirmation of this finding in a larger prospective trial is warranted to explore this potential benefit for the management of preterm birth in future.

Clinical Application of Quantitative Foetal Fibronectin for the Prediction of Preterm Birth in Symptomatic Women.

AIM: To evaluate the clinical application of the new Hologic quantitative foetal fibronectin (qfFN) bedside test for the prediction of spontaneous preterm birth (sPTB) in patients with symptoms suggestive of spontaneous threatened preterm labour (sPTL). METHODS: A prospective observational study with 154 pregnant women presenting signs and symptoms of sPTL was conducted. These women were subjected to a qfFN test between 22 and 35 weeks of gestation For each cut-off threshold, the ability to predict sPTB at within 14 days of conducting the test and <37 weeks was assessed by calculating the positive predictive value (PPV), negative predictive value (NPV), likelihood ratios, odds ratios, sensitivity, and specificity. RESULTS: For the outcome of delivery within 14 days of the test, qfFN <10 ng/mL had a 100% NPV and >200 ng/mL produced a 50.0% PPV; thus, qfFN added enhanced discrimination between high- and low-risk patients. The overall rate of sPTB (<37) was 13.3% (16/120), which increased progressively with increasing levels of fFN, with rates of 9.8% (8/81), 11.5% (3/26), 14.2% (1/7), 50% (3/6) within the 4 categories (fFN 0-9, 10-49, 50-200, 200+) respectively. CONCLUSIONS: The use of the qfFN testing in symptomatic patients allowed for more accurate identification of women at risk of sPTB and thus more directed management.

Changes in myometrial expression of progesterone receptor membrane components 1 and 2 are associated with human parturition at term.

While the exact mechanism of human parturition remains unknown, functional progesterone withdrawal is believed to play a key regulatory role. Progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) are putative progesterone receptors and the aim of this project was to investigate their expression in human myometrium. Human term myometrium was obtained from the lower uterine segment incision in women undergoing elective (not-in-labour, NIL; n=11) and emergency Caesarean sections (in-labour, IL; n=10), following written consent. PGRMC1 and 2 expression was quantified using real-time reverse transcription polymerase chain reaction and western blot. Subcellular localisation was performed by immunohistochemistry and immunofluorescence. There was a significant decrease in PGRMC1 mRNA (P=0.0317) and protein expression (P=0.0151) in IL myometrium, compared with NIL myometrium. PGRMC2 mRNA expression (P=0.0151) was also decreased in IL myometrium, compared with NIL myometrium. Immunostaining studies confirmed the presence of PGRMC1 and 2 in smooth-muscle cells. Expression was perinuclear in NIL myometrium and more generalised and cytoplasmic in IL myometrium. The decrease in PGRMC1 expression and the translocation away from a perinuclear location for both PGRMC1 and 2 could contribute to a functional progesterone withdrawal that may ultimately initiate parturition.

Maternal Thyroid Disease and Preterm Birth: Systematic Review and Meta-Analysis.

CONTEXT: Thyroid disease in pregnancy is increasing with rising average maternal ages in developed countries. The evidence for an association between preterm birth and thyroid disease has been confounded by small studies with varying outcomes and methodology. OBJECTIVE: The aim of this meta-analysis is to review the literature regarding thyroid disease including subclinical and overt hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia and the specific outcome of preterm birth. DATA SOURCES: A search of PubMed and Embase databases was performed in May 2015. A fixed-effects model was used to calculate the overall combined odds ratio (OR) with its corresponding 95% confidence interval (95% CI) to evaluate the relationship between thyroid disease and preterm delivery. STUDY SELECTION: Studies were considered eligible if they met the following criteria: prospective cohort study or a case control study; the exposure of interest was maternal thyroid disease, including subclinical hypothyroidism, overt hypothyroidism, hyperthyroidism, or isolated hypothyroxinemia; the outcome of interest was preterm delivery; and data regarding numbers of preterm births in each cohort were reported. DATA EXTRACTION: Data were recorded in a database evidence table including any incidence data for maternal thyroid disease and preterm birth compared to a reference group. DATA SYNTHESIS: Fourteen cohort studies and one case control study involving 2 532 704 participants were included. The combined OR of preterm delivery for pregnant women with overt hypothyroidism compared with the reference group was 1.19 (95% CI, 1.12-1.26; P < .00001). There was also a significant risk of preterm birth in women with hyperthyroidism (OR, 1.24 [95%, CI 1.17-1.31]; P < .00001). Subclinical hypothyroidism and isolated hypothyroxinemia showed no significant increase in OR. Sensitivity analysis made no change to these results. CONCLUSION: Both overt hypothyroidism and hyperthyroidism are associated with a small but statistically significant increase in OR for preterm birth not seen in subclinical hypothyroidism or isolated hypothyroxinemia.

Factors associated with spontaneous preterm birth risk assessed by transvaginal ultrasound following cervical cerclage.

OBJECTIVE: To determine the predictive value of various cervical length measurements postcerclage for the outcome of preterm birth following both elective and rescue cerclage. MATERIALS AND METHODS: Over a five-year period, we identified 59 women who had a transvaginal cerclage inserted followed by serial cervical length measurement. Of these, 18 were elective cerclages placed at 14 weeks of gestation on the basis of a history of cervical insufficiency and 41 were rescue cerclages performed at gestations ranging from 17 to 23 weeks following a diagnosis of shortened cervix on ultrasound. The women were asymptomatic throughout. RESULTS: There was a strong correlation between cervical length postcerclage and gestation at delivery. For both groups, preterm birth could be predicted by the total cervical length. In the rescue cerclage group, the change in cervical length was predictive, with positive changes associated with later gestation at delivery. The presence of funnelling was predictive of preterm birth in the elective cerclage group only. CONCLUSION: Transvaginal cervical length measurement is useful in the prediction of preterm birth postcerclage placement. Serial cervical length measurement postcerclage may assist with timely addition of interventions such, progesterone and antenatal cortico steroids for fetal lung maturation.

Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women.

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and ß-inhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells. We show that hERG channel activity suppresses contraction amplitude and duration before labour, thereby facilitating quiescence. During established labour, expression of ß-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low ß-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery.

A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin.

Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable menorrhagia. Histopathological examination of a subsequent hysterectomy specimen revealed a bulky uterus, a poorly developed secretory endometrium with decidualization of the stroma and chronic endometritis, as well as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were measured in the plasma of this and 234 other patients. Nine (3.8%) patients tested positive. The titer of anticalreticulin IgG autoantibody in the sole case with adenomyosis was approximately 8 times the average of other positive-testing samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a high titer, blocking anticalreticulin autoantibody may directly increase the risk that adenomyosis might develop. It is also possible that the expansion of endometrial glandular tissue, as well as elevated estrogens, during adenomyosis may lead to elevated calreticulin, which induces an autoimmune reaction to it. Further study is required to determine whether there is a significant association between adenomyosis and the prevalence of calreticulin autoantibodies.