Neonatal and Developmental Outcomes of Late Preterm and Early Term Birth

Research suggests increased risk for adverse outcomes associated with late preterm (34-36 weeks) and early term (37-38 weeks) birth versus full term (39-41 weeks). However, it remains unclear to what extent these outcomes are associated with physiological immaturity or factors leading to or associated with early birth. The first objective was to elucidate the role of gestational age in determining risk of poor neonatal outcomes in the context of biological determinants of preterm birth. A retrospective cohort study of singletons delivered at 34-41 weeks to London-Middlesex (Canada) mothers was conducted using perinatal and discharge abstract databases (N=38,807, 2002-2011). Modified Poisson regression showed increased risk for NICU triage/admission and respiratory morbidity among infants born late preterm and early term. The effect of gestational age was partially explained by biological determinants (infection and inflammation, placental ischemia and other hypoxia, other [diabetes/hydramnios]) acting through gestational age. Placental ischemia and other hypoxia exacerbated the effect of gestational age on poor outcomes. The second objective was to elucidate the role of gestational age in determining risk of poor developmental outcomes in the context of proximal social processes. A secondary analysis of singletons delivered at 34-41 weeks was conducted using the National Longitudinal Survey of Children and Youth (N=15,099, 2-3 years; N=12,203, 4-5 years). Modified Poisson regression did not show increased risk for developmental delay or receptive vocabulary delay among children born late preterm or early term. Proximal social processes (parenting interactions, effectiveness, consistency) did not modify the effect of gestational age but were strong predictors of poor outcomes. The third objective, secondary to central analyses, was to examine associations between biological determinants of preterm birth and gestational age among spontaneous singleton births (perinatal database; N=17,678). Multinomial logistic regression showed associations between these pathological processes and both late preterm and early term birth. Poor neonatal outcomes among infants born late preterm and early term are due to physiological immaturity and also to biological determinants of preterm birth acting through and with gestational age to produce poor outcomes. Beyond the neonatal period, social factors are the most important influences on development in births close to full term

Changes in Smoking During Pregnancy in Ontario, 1995 to 2010: Results From the Canadian Community Health Survey

Objective: The objectives of this study were (1) to examine changes in smoking behaviour across time in pregnant women in Ontario (relative to non-pregnant women and men) and (2) to assess whether, among pregnant women, changes across time vary as a function of sociodemographic characteristics. Methods: This study used data from the Canadian Community Health Survey. The study sample included 15- to 49-year-old residents of Ontario. Multivariable logistic regression, with interactions between time period and the characteristic of interest, was used to examine whether changes varied across time according to (1) group (pregnant women, non-pregnant women, men; two-year intervals, 2001 to 2010) and (2) pregnant subgroup (maternal age, maternal marital status, maternal education; 1995 to 2000 [n = 3745], 2001 to 2005 [n = 5084], and 2006 to 2010 [n = 2900]). Results: A decrease in the prevalence of smoking across time was seen in all groups but was smaller in pregnant women than in non-pregnant women (23.5% vs. 30.8%). Among pregnant women, interactions between time period and maternal age, maternal marital status, and maternal education were statistically significant. The prevalence of smoking during pregnancy decreased in older, married, and more highly educated women, but increased in younger women (by 8.2%) and less educated women (by 12.8%). Although the prevalence of smoking during pregnancy decreased in unmarried women, the change was smaller than in married women. Conclusion: Although the prevalence of smoking in pregnant women is decreasing over time, the decrease is smaller than that in non-pregnant women. Pregnant subgroups particularly resistant to change include younger, unmarried, and less educated mothers. These findings suggest there are subgroups that should be targeted more deliberately by public health interventions

Neonatal morbidity associated with late preterm and early term birth: The roles of gestational age and biological determinants of preterm birth

Background: The aim of this study was to elucidate the role of gestational age in determining the risk of neonatal morbidity among infants born late preterm (34-36 weeks) and early term (37-38 weeks) compared with those born full term (39-41 weeks) by examining the contribution of gestational age within the context of biological determinants of preterm birth.Methods: This was a retrospective cohort study. The sample included singleton live births with no major congenital anomalies, delivered at 34-41 weeks of gestation to London-Middlesex (Canada) mothers in 2002-11. Data from a city-wide perinatal database were linked with discharge abstract data. Multivariable models used modified Poisson regression to directly estimate adjusted relative risks (aRRs). The roles of gestational age and biological determinants of preterm birth were further examined using mediation and moderation analyses.Results: Compared with infants born full term, infants born late preterm and early term were at increased risk for neonatal intensive care unit triage/admission [late preterm aRR = 6.14, 95% confidence interval (CI) 5.63, 6.71; early term aRR = 1.54, 95% CI 1.41, 1.68] and neonatal respiratory morbidity (late preterm aRR = 6.16, 95% CI 5.39, 7.03; early term aRR = 1.46, 95% CI 1.29, 1.65). The effect of gestational age was partially explained by biological determinants of preterm birth acting through gestational age. Moreover, placental ischaemia and other hypoxia exacerbated the effect of gestational age on poor outcomes.Conclusions: Poor outcomes among infants born late preterm and early term are not only due to physiological immaturity but also to biological determinants of preterm birth acting through and with gestational age to produce poor outcomes. © The Author 2013; all rights reserved

Gestational age impacts birth to placental weight ratio and umbilical cord oxygen values with implications for the fetal oxygen margin of safety

Background: We determined the impact of gestational age (GA) from near term to term to post-term on birth/placental weight ratio and cord oxygen values with implications for placental transport efficiency for oxygen, fetal O2 consumption relative to delivery or fractional O2 extraction, and oxygen margin of safety. Materials and methods: A hospital database was used to obtain birth/placental weight ratios, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA \u3e 34 completed weeks (N=69,852). Oxygen saturation was calculated from the cord PO2 and pH data, while fractional O2 extraction was calculated from the oxygen saturation data. The effect of GA grouping on birth/placental weight ratio, cord PO2, O2 saturation, and fractional O2 extraction values, was examined in all patients adjusting for pregnancy and labor/delivery covariates, and in a subset of low-risk patients. Results: Birth/placental weight ratio and umbilical venous O2 values increased with advancing GA, supporting the conjecture of increasing placental transport efficiency for oxygen. However, umbilical arterial O2 values decreased while fractional O2 extraction increased with successive GA groupings, indicating that fetal O2 consumption must be increasing relative to delivery. Conclusions: Fetal O2 consumption can be seen as ever ‘outgrowing’ O2 delivery over the last weeks of pregnancy and leading to a continued lowering in systemic oxygen levels. While this lowering in oxygen may trigger feedback mechanisms with survival benefit, the ‘oxygen margin of safety’ will also be lowered increasing perinatal morbidity and mortality which appear to be hypoxia related

Physical health of autistic girls and women: a scoping review.

BACKGROUND: There is a growing recognition of sex and gender influences in autism. Increasingly, studies include comparisons between sexes or genders, but few have focused on clarifying the characteristics of autistic girls'/women's physical health. METHODS: A scoping review was conducted to determine what is currently known about the physical health of autistic girls/women. We screened 1112 unique articles, with 40 studies meeting the inclusion criteria. We used a convergent iterative process to synthesize this content into broad thematic areas. RESULTS: Autistic girls/women experience more overall physical health challenges compared to non-autistic girls/women and to autistic boys/men. Emerging evidence suggests increased prevalence of epilepsy in autistic girls/women compared to non-autistic girls/women and to autistic boys/men. The literature also suggests increased endocrine and reproductive health conditions in autistic girls/women compared to non-autistic girls/women. Findings regarding gastrointestinal, metabolic, nutritional, and immune-related conditions are preliminary and inconsistent. LIMITATIONS: The literature has substantial heterogeneity in how physical health conditions were assessed and reported. Further, our explicit focus on physical health may have constrained the ability to examine interactions between mental and physical health. The widely differing research aims and methodologies make it difficult to reach definitive conclusions. Nevertheless, in keeping with the goals of a scoping review, we were able to identify key themes to guide future research. CONCLUSIONS: The emerging literature suggests that autistic girls/women have heightened rates of physical health challenges compared to non-autistic girls/women and to autistic boys/men. Clinicians should seek to provide holistic care that includes a focus on physical health and develop a women's health lens when providing clinical care to autistic girls/women

Maternal and infant outcomes associated with lithium use in pregnancy

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse

Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy

Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when 'ambiguous' medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests

The High-Energy Radiation Environment Around a 10 Gyr M Dwarf: Habitable at Last?

High levels of X-ray and UV activity on young M dwarfs may drive rapid atmospheric escape on temperate, terrestrial planets orbiting within the liquid water habitable zone. However, secondary atmospheres on planets orbiting older, less active M dwarfs may be stable and present more promising candidates for biomarker searches. We present new HST and Chandra observations of Barnard's Star (GJ 699), a 10 Gyr old M3.5 dwarf, acquired as part of the Mega-MUSCLES program. Despite the old age and long rotation period of Barnard's star, we observe two FUV ($\delta_{130}$ $\approx$ 5000s; $E_{130}$ $\approx$ 10$^{29.5}$ erg each) and one X-ray ($E_{X}$ $\approx$ 10$^{29.2}$ erg) flares, and estimate a high-energy flare duty cycle (defined here as the fraction of the time the star is in a flare state) of $\sim$ 25\%. A 5 A - 10 $\mu$m SED of GJ 699 is created and used to evaluate the atmospheric stability of a hypothetical, unmagnetized terrestrial planet in the habitable zone ($r_{HZ}$ $\sim$ 0.1 AU). Both thermal and non-thermal escape modeling indicate (1) the $quiescent$ stellar XUV flux does not lead to strong atmospheric escape: atmospheric heating rates are comparable to periods of high solar activity on modern Earth, and (2) the $flare$ environment could drive the atmosphere into a hydrodynamic loss regime at the observed flare duty cycle: sustained exposure to the flare environment of GJ 699 results in the loss of $\approx$ 87 Earth atmospheres Gyr$^{-1}$ through thermal processes and $\approx$ 3 Earth atmospheres Gyr$^{-1}$ through ion loss processes, respectively. These results suggest that if rocky planet atmospheres can survive the initial $\sim$ 5 Gyr of high stellar activity, or if a second generation atmosphere can be formed or acquired, the flare duty cycle may be the controlling stellar parameter for the stability of Earth-like atmospheres around old M stars.Comment: Accepted to A

Gene Amplification, ABC Transporters and Cytochrome P450s: Unraveling the Molecular Basis of Pyrethroid Resistance in the Dengue Vector, Aedes aegypti

Dengue is the most rapidly spreading arboviral infection of humans and each year there are 50–100 million cases of dengue fever. There is no vaccine or drug to prevent dengue infection so control of the mosquitoes that transmit this virus is the only option to reduce transmission. Removing mosquito habitats close to human homes can be effective but in reality most dengue control programmes rely on a small number of chemical insecticides. Therefore, when the mosquito vectors develop resistance to the available insecticides, dengue control is jeopardized. In this study we examined the causes of resistance to the insecticide class most commonly used in mosquito control, the pyrethroids. We found that a group of genes, which have been implicated in detoxifying these insecticides in other populations of dengue vectors, were highly over expressed in both these Caribbean populations and we investigated the molecular basis of this increased expression. The next steps, which will be a considerable challenge, are to utilize this information to develop effective means of restoring insecticide susceptibility in dengue vectors

Pelvic Chlamydial Infection Predisposes to Ectopic Pregnancy by Upregulating Integrin ?1 to Promote Embryo-tubal Attachment

Tubal ectopic pregnancies are a leading cause of global maternal morbidity and mortality. Previous infection with Chlamydia trachomatis is a major risk factor for tubal embryo implantation but the biological mechanism behind this association is unclear. Successful intra-uterine embryo implantation is associated with increased expression of endometrial “receptivity” integrins (cell adhesion molecules).We examined integrin expression in Fallopiantubes of women with previous C. trachomatis infection, in mice experimentally infected with C. trachomatis, in immortalised human oviductal epithelial cells (OE-E6/E7) and in an in vitro model of human embryo attachment (trophoblast spheroid-OE-E6/7 cell co-culture). Previous exposure with C. trachomatis increased Fallopian tube/oviduct integrin-subunit beta-1 (ITGB1) in women and mice compared to controls. C. trachomatis increased OEE6/E7 cell ITGB1 expression and promoted trophoblast attachment to OE-E6/E7 cellswhichwas negated by anti-ITGB1-antibody.We demonstrate that infection with C. trachomatis increases tubal ITGB1 expression, predisposing to tubal embryo attachment and ectopic pregnancy