Association between interpregnancy interval and pregnancy complications by history of complications: A population-based cohort study

Objective: To examine if the association between interpregnancy interval (IPI) and pregnancy complications varies by the presence or absence of previous complications. Design and setting Population-based longitudinally linked cohort study in Western Australia (WA). Participants: Mothers who had their first two (n=252 368) and three (n=96 315) consecutive singleton births in WA between 1980 and 2015. Outcome measures: We estimated absolute risks (AR) of preeclampsia (PE) and gestational diabetes (GDM) for 3–60 months of IPI according to history of each outcome. We modelled IPI using restricted cubic splines and reported adjusted relative risk (RRs) with 95% CI at 3, 6, 12, 24, 36, 48 and 60 months, with 18 months as reference. Results: Risks of PE and GDM were 9.5%, 2.6% in first pregnancies, with recurrence rates of 19.3% and 41.5% in second pregnancy for PE and GDM, respectively. The AR of GDM ranged from 30% to 43% across the IPI range for mothers with previous GDM compared with 2%–8% for mothers without previous GDM. For mothers with no previous PE, greater risks were observed for IPIs at 3 months (RR 1.24, 95% CI 1.07 to 1.43) and 60 months (RR 1.40, 95% CI 1.29 to 1.53) compared with 18 months. There was insufficient evidence for increased risk of PE at shorter IPIs of <18 months for mothers with previous PE. Shorter IPIs of <18 months were associated with lower risk than at IPIs of 18 months for mothers with no previous GDM. Conclusions: The associations between IPIs and risk of PE or GDM on subsequent pregnancies are modified by previous experience with these conditions. Mothers with previous complications had higher absolute, but lower RRs than mothers with no previous complications. However, IPI remains a potentially modifiable risk factor for mothers with previous complicated pregnancies.Amanuel Tesfay Gebremedhin, Gizachew Assefa Tessema, Annette K Regan, Gavin F Pereir

Re-evaluation of gestational age as a predictor for subsequent preterm birth

Background: To evaluate gestational age as a predictor of subsequent preterm birth. Materials and methods: This was a retrospective birth cohort study to evaluate gestational age as a predictor of subsequent preterm birth. Participants were mothers who gave birth to their first two children in Western Australia, 1980–2015 (N = 255,151 mothers). For each week of final gestational age of the first birth, we calculated relative risks (RR) and absolute risks (AR) of subsequent preterm birth defined as final gestational age before 28, 32, 34 and <37 weeks. Risks were unadjusted to preserve risk factor profiles at each week of gestation. Results: The relative risks of second birth before 28, 32, and 34 weeks’ gestation were all approximately twenty times higher for mothers whose first birth had a gestational age of 22 to 30 weeks compared to those whose first birth was at 40 weeks’ gestation. The absolute risks of second birth before 28, 32, and 34 weeks’ gestation for these mothers had upper confidence limits that were all less than 16.74%. The absolute risk of second birth before 37 weeks was highest at 32.11% (95% CI: 30.27, 34.02) for mothers whose first birth was 22 to 30 weeks’ gestation. For all gestational ages of the first child, the lowest quartile and median gestational age of the second birth were at least 36 weeks and at least 38 weeks, respectively. Sensitivity and positive predictive values were all below 35%. Conclusion: Relative risks of early subsequent birth increased markedly with decreasing gestational age of the first birth. However, absolute risks of clinically significant preterm birth (<28 weeks, <32 weeks, <34 weeks), sensitivity and positive predictive values remained low. Early gestational age is a strong risk factor but a poor predictor of subsequent preterm birth.Elizabeth Pereira, Gizachew Tessema, Mika Gissler, Annette K. Regan, Gavin Pereir

Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation

Objectives: In 2013, the Follow-up and Active Surveillance of Trivalent Influenza Vaccine in Mums (FASTMum) program began using short message service (SMS) to collect adverse event information in pregnant women who recently received trivalent influenza vaccine (TIV). This study was designed to compare data collected via SMS and telephone for the purposes of monitoring vaccine safety. Methods: A number of 344 women who received TIV were randomly assigned to a telephone interview group. They were telephoned seven days post-vaccination and administered a standard survey soliciting any adverse events following immunisation (AEFI) they experienced. They were matched by brand of vaccine, age group, and residence to 344 women who were sent a SMS seven days post-vaccination. The SMS solicited similar information. AEFI reported by SMS and telephone interview were compared by calculating risk ratios. Results: Response rate was higher to SMS compared to telephone interview (90.1% vs. 63.9%). Women who were surveyed by SMS were significantly less likely to report an AEFI compared to women who were surveyed by telephone (RR: 0.41; 95% CI: 0.29–0.59). The greatest discrepancies between SMS and telephone interview were for self-reported injection site reactions (3.1% vs. 16.8%) and unsolicited (or “other”) events (11.4% vs. 4.1%). Data collected by SMS was significantly timelier. Conclusions: Data collection by SMS results in significantly improved response rates and timeliness of vaccine safety data. Systems which incorporate SMS could be used to more rapidly detect safety signals and promote more rapid public health response to vaccine quality issues

Stillbirth risk prediction using machine learning for a large cohort of births from Western Australia, 1980–2015

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression

Stillbirth risk prediction using machine learning for a large cohort of births from Western Australia, 1980–2015

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression

Interpregnancy intervals and adverse birth outcomes in high-income countries: an international cohort study

Published: July 19, 2021Background: Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue.Methods: We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980–2016), Finland (1987–2017), Norway (1980–2016) and the United States (California) (1991–2012). IPI was calculated based on the time difference between two dates—the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). Results: Compared to an IPI of 18–23 months, there was insufficient evidence for an association between IPI 24 month IPIs. Conclusions: We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.Gizachew A. Tessema, M. Luke Marinovich, Siri E. Håberg, Mika Gissler, Jonathan A. Mayo, Natasha Nassar ... et al

Broken seniority symmetry in the semimagic proton mid-shell nucleus ⁹⁵Rh

Lifetime measurements of low-lying excited states in the semimagic ( N = 50 ) nucleus 95Rh have been performed by means of the fast-timing technique. The experiment was carried out using γ -ray detector arrays consisting of LaBr3(Ce) scintillators and germanium detectors integrated into the DESPEC experimental setup commissioned for the Facility for Antiproton and Ion Research (FAIR) Phase-0, Darmstadt, Germany. The excited states in 95Rh were populated primarily via the β decays of 95Pd nuclei, produced in the projectile fragmentation of a 850 MeV/nucleon 124Xe beam impinging on a 4 g / cm2 9Be target. The deduced electromagnetic E2 transition strengths for the γ -ray cascade within the multiplet structure depopulating from the isomeric Iπ = 21 / 2+ state are found to exhibit strong deviations from predictions of standard shell model calculations which feature approximately conserved seniority symmetry. In particular, the observation of a strongly suppressed E2 strength for the 13 / 2+ → 9 / 2+ ground state transition cannot be explained by calculations employing standard interactions. This remarkable result may require revision of the nucleon-nucleon interactions employed in state-of-the-art theoretical model calculations, and might also point to the need for including three-body forces in the Hamiltonian

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission., Using longitudinal samples from the ACTIV-2 clinical trial of the monoclonal antibody bamlinivimab, Boucau et al. investigate the duration of shedding culturable virus. Treatment with monoclonal antibody results in rapid clearance of culturable virus. The emergence of mutations in a subset of participants coincides with viral rebound and resurgent culturable virus

The shape of the <i>T</i>_z = +1 nucleus ⁹⁴Pd and the role of proton-neutron interactions on the structure of its excited states

Reduced transition probabilities have been extracted between excited, yrast states in the N = Z + 2 nucleus 94Pd. The transitions of interest were observed following decays of the Iπ = 14+ , Ex = 2129-keV isomeric state, which was populated following the projectile fragmentation of a 124Xe primary beam at the GSI Helmholtzzentrum für Schwerionenforschung accelerator facility as part of FAIR Phase-0. Experimental information regarding the reduced E2 transition strengths for the decays of the yrast 8+ and 6+ states was determined following isomer-delayed Eγ1 − Eγ2 − △T2,1 coincidence method, using the LaBr3(Ce)-based FATIMA fast-timing coincidence gamma-ray array, which allowed direct determination of lifetimes of states in 94Pd using the Generalized Centroid Difference (GCD) method. The experimental value for the half-life of the yrast 8+ state of 755(106) ps results in a reduced transition probability of B(E2:8+ →6+ ) = 205+34 −25 e2fm4 , which enables a precise verification of shell-model calculations for this unique system, lying directly between the N = Z line and the N = 50 neutron shell closure. The determined B(E2) value provides an insight into the purity of (g9/2)n configurations in competition with admixtures from excitations between the (lower) N = 3 pf and (higher) N = 4 gds orbitals for the first time. The results indicate weak collectivity expected for near-zero quadrupole deformation and an increasing importance of the T = 0 proton-neutron interaction at N = 48

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation