Cognitive development following ART: effect of choice of comparison group, confounding and mediating factors

BACKGROUND: Epidemiological studies have examined the health of children born after assisted reproductive technology (ART), with contradictory results. In this article, we address the question 'Do singletons born after ART have a poorer cognitive developmental outcome at 3 years of age?' We assess the implications of using different comparison groups, and discuss appropriate analytical approaches for the control of confounding and mediating variables. METHODS: Data were drawn from the Millennium Cohort Study. Interviews captured sociodemographic, behavioural and pregnancy information. Developmental assessments conducted at age three included the British Ability Scales II Naming Vocabulary (BAS-NV) instrument. We compared ART infants (born after IVF or ICSI) to four comparison groups: a 'matched' group; a 'subfertile' group (time to conception >12 months); a 'fertile' group (time to conception <12 months); and an 'any spontaneous conceptions' group. Linear regression provided estimates of the difference in mean BAS-NV scores in the ART and comparison groups; both unadjusted estimates and those adjusted for confounding and mediating factors are presented. RESULTS: In the unadjusted analyses, ART children gained significantly better BAS-NV test results than did the comparison group children. When converted to an estimate of developmental age gap, ART children were 2.5, 2.7, 3.6 and 4.5 months ahead of the 'matched', 'subfertile', 'fertile' and 'spontaneous conception' children, respectively. After adjusting for confounding and mediating factors, the differences were reduced, and were not statistically significant. CONCLUSIONS: ART is not associated with poorer cognitive development at 3 years. We have highlighted methodological considerations for researchers planning to study the effect of infertility and ART on childhood outcomes

Pillared two-dimensional metal-organic frameworks based on a lower-rim acid appended calix[4]arene

Solvothermal reactions of the lower-rim functionalized diacid calix[4]arene 25,27-bis(methoxycarboxylic acid)-26,28-dihydroxy-4-tert-butylcalix[4]arene (LH₂) with Zn(NO₃)₂•6H₂O and the dipyridyl ligands 4,4/-bipyridyl (4,4/-bipy), 1,2-di(4-pyridyl)ethylene (DPE) or 4,4/-azopyridyl (4,4/-azopy) afforded a series of 2-D structures of the formulae {[Zn(4,4/-bipy)(L)]•2¼DEF}n (1), {[Zn₂(L)(DPE)]•DEF}n (2) and {[Zn(OH₂)₂(L)(4,4/-azopy)]•DEF}n (3) (DEF = diethylformamide)

The Birthplace in England national prospective cohort study: further analyses to enhance policy and service delivery decision-making for planned place of birth

Background: Evidence from the Birthplace in England Research Programme supported a policy of offering ‘low risk’ women a choice of birth setting, but a number of unanswered questions remained. Aims: This project aimed to provide further evidence to support the development and delivery of maternity services and inform women’s choice of birth setting: specifically, to explore maternal and organisational factors associated with intervention, transfer and other outcomes in each birth setting in ‘low risk’ and ‘higher risk’ women. Design: Five component studies using secondary analysis of the Birthplace prospective cohort study (studies 2–5) and ecological analysis of unit/NHS trust-level data (studies 1 and 5). Setting: Obstetric units (OUs), alongside midwifery units (AMUs), freestanding midwifery units (FMUs) and planned home births in England. Participants: Studies 1–4 focused on ‘low risk’ women with ‘term’ pregnancies planning vaginal birth in 43 AMUs (n = 16,573), in 53 FMUs (n = 11,210), at home in 147 NHS trusts (n = 16,632) and in a stratified, random sample of 36 OUs (n = 19,379) in 2008–10. Study 5 focused on women with pre-existing medical and obstetric risk factors (‘higher risk’ women). Main outcome measures: Interventions (instrumental delivery, intrapartum caesarean section), a measure of low intervention (‘normal birth’), a measure of spontaneous vaginal birth without complications (‘straightforward birth’), transfer during labour and a composite measure of adverse perinatal outcome (‘intrapartum-related mortality and morbidity’ or neonatal admission within 48 hours for > 48 hours). In studies 1 and 3, rates of intervention/maternal outcome and transfer were adjusted for maternal characteristics. Analysis: We used (a) funnel plots to explore variation in rates of intervention/maternal outcome and transfer between units/trusts, (b) simple, weighted linear regression to evaluate associations between unit/trust characteristics and rates of intervention/maternal outcome and transfer, (c) multivariable Poisson regression to evaluate associations between planned place of birth, maternal characteristics and study outcomes, and (d) logistic regression to investigate associations between time of day/day of the week and study outcomes. Results: Study 1 – unit-/trust-level variations in rates of interventions, transfer and maternal outcomes were not explained by differences in maternal characteristics. The magnitude of identified associations between unit/trust characteristics and intervention, transfer and outcome rates was generally small, but some aspects of configuration were associated with rates of transfer and intervention. Study 2 – ‘low risk’ women planning non-OU birth had a reduced risk of intervention irrespective of ethnicity or area deprivation score. In nulliparous women planning non-OU birth the risk of intervention increased with increasing age, but women of all ages planning non-OU birth experienced a reduced risk of intervention. Study 3 – parity, maternal age, gestational age and ‘complicating conditions’ identified at the start of care in labour were independently associated with variation in the risk of transfer in ‘low risk’ women planning non-OU birth. Transfers did not vary by time of day/day of the week in any meaningful way. The duration of transfer from planned FMU and home births was around 50–60 minutes; transfers for ‘potentially urgent’ reasons were quicker than transfers for ‘non-urgent’ reasons. Study 4 – the occurrence of some interventions varied by time of the day/day of the week in ‘low risk’ women planning OU birth. Study 5 – ‘higher risk’ women planning birth in a non-OU setting had fewer risk factors than ‘higher risk’ women planning OU birth and these risk factors were different. Compared with ‘low risk’ women planning home birth, ‘higher risk’ women planning home birth had a significantly increased risk of our composite adverse perinatal outcome measure. However, in ‘higher risk’ women, the risk of this outcome was lower in planned home births than in planned OU births, even after adjustment for clinical risk factors. Conclusions: Expansion in the capacity of non-OU intrapartum care could reduce intervention rates in ‘low risk’ women, and the benefits of midwifery-led intrapartum care apply to all ‘low risk’ women irrespective of age, ethnicity or area deprivation score. Intervention rates differ considerably between units, however, for reasons that are not understood. The impact of major changes in the configuration of maternity care on outcomes should be monitored and evaluated. The impact of non-clinical factors, including labour ward practices, staffing and skill mix and women’s preferences and expectations, on intervention requires further investigation. All women planning non-OU birth should be informed of their chances of transfer and, in particular, older nulliparous women and those more than 1 week past their due date should be advised of their increased chances of transfer. No change in the guidance on planning place of birth for ‘higher risk’ women is recommended, but research is required to evaluate the safety of planned AMU birth for women with selected relatively common risk factors. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Perinatal and maternal outcomes in planned home and obstetric unit births in women at ‘higher risk’ of complications: secondary analysis of the Birthplace national prospective cohort study

Objective: To explore and compare perinatal and maternal outcomes in women at ‘higher risk’ of complications planning home versus obstetric unit (OU) birth. Design: Prospective cohort study. Setting: OUs and planned home births in England. Population: 8180 ‘higher risk’ women in the Birthplace cohort. Methods: We used Poisson regression to calculate relative risks adjusted for maternal characteristics. Sensitivity analyses explored possible effects of differences in risk between groups and alternative outcome measures. Main outcome measures: Composite perinatal outcome measure encompassing ‘intrapartum related mortality and morbidity’ (intrapartum stillbirth, early neonatal death, neonatal encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured humerus or clavicle) and neonatal admission within 48 hours for more than 48 hours. Two composite maternal outcome measures capturing intrapartum interventions/adverse maternal outcomes and straightforward birth. Results: The risk of ‘intrapartum related mortality and morbidity’ or neonatal admission for more than 48 hours was lower in planned home births than planned OU births [adjusted relative risks (RR) 0.50, 95% CI 0.31–0.81]. Adjustment for clinical risk factors did not materially affect this finding. The direction of effect was reversed for the more restricted outcome measure ‘intrapartum related mortality and morbidity’ (RR adjusted for parity 1.92, 95% CI 0.97–3.80). Maternal interventions were lower in planned home births. Conclusions: The babies of ‘higher risk’ women who plan birth in an OU appear more likely to be admitted to neonatal care than those whose mothers plan birth at home, but it is unclear if this reflects a real difference in morbidity. Rates of intrapartum related morbidity and mortality did not differ statistically significantly between settings at the 5% level but a larger study would be required to rule out a clinically important difference between the groups

Mass Measurement of 27^{27}P for Improved Type-I X-ray Burst Modeling

Light curves are the primary observable of type-I x-ray bursts. Computational x-ray burst models must match simulations to observed light curves. Most of the error in simulated curves comes from uncertainties in $rp$ process reaction rates, which can be reduced via precision mass measurements of neutron-deficient isotopes in the $rp$ process path. We perform a precise atomic mass measurement of $^{27}$P and use this new measurement to update existing type-I x-ray burst models to produce an improved light curve. High-precision Penning trap mass spectrometry was used to determine the atomic mass of $^{27}$P. Modules for Experiments in Stellar Astrophysics (MESA) was then used to simulate x-ray bursts using a 1D multi-zone model to produce updated light curves. The mass excess of $^{27}$P was measured to be -670.7$\pm$ 0.6 keV, a fourteen-fold precision increase over the mass reported in AME2020. The $^{26}$Si($p, \gamma$)$^{27}$P and reverse photodisintegration reaction rates have been determined to a higher precision based on the new, high precision mass measurement of $^{27}$P, and MESA light curves generated using these rates. Changes in the mass of $^{27}$P seem to have minimal effect on XRB light curves, even in burster systems tailored to maximize impact. The mass of $^{27}$P does not play a significant role in x-ray burst light curves. It is important to understand that more advanced models don't just provide more precise results, but often qualitatively different ones. This result brings us a step closer to being able to extract stellar parameters from individual x-ray burst observations. In addition, the Isobaric Multiplet Mass Equation (IMME) has been validated for the $A=27, T=3/2$ quartet, but only after including a small, theoretically predicted cubic term and utilizing an updated excitation energy for the $T=3/2$ isobaric analogue state of $^{27}$Si.Comment: 8 pages, 7 figure

Systematic study of trace radioactive impurities in candidate construction materials for EXO-200

The Enriched Xenon Observatory (EXO) will search for double beta decays of 136Xe. We report the results of a systematic study of trace concentrations of radioactive impurities in a wide range of raw materials and finished parts considered for use in the construction of EXO-200, the first stage of the EXO experimental program. Analysis techniques employed, and described here, include direct gamma counting, alpha counting, neutron activation analysis, and high-sensitivity mass spectrometry.Comment: 32 pages, 6 figures. Expanded introduction, added missing table entry. Accepted for publication in Nucl. Instrum. Meth.