Phenotypic heterogeneity in cystic fibrosis

We have confirmed heterogenity in CF using a different combination of primary clinical variables than those used in previous studies. Subgroupings of individuals with similar levels of sweat chloride were independent of the clustering based on level of pancreatic enzyme supplementation and degree of pulmonary involvement. Data from families with multiple CF children are consistent with the hypothesis that the genetic etiology of CF involves two or more genes that modify the expression of the primary gene defect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38234/1/1320130209_ftp.pd

Mood and anxiety disorders in very preterm/very low-birth weight individuals from 6 to 26 years

Background Very preterm (<32 weeks’ gestational age; VP) or very low–birth weight (<1,500 g; VLBW) birth has been associated with increased risk for anxiety and mood disorders and less partnering in adulthood. The aim was to test whether (a) VP/VLBW are at increased risk of any anxiety or mood disorders from 6 to 26 years compared with term-born individuals; (b) social support from romantic partners is associated with protection from anxiety and mood disorders; and (c) VP/VLBW adults’ lower social support mediates their risk for any anxiety and mood disorders. Methods Data are from a prospective geographically defined longitudinal whole-population study in South Bavaria (Germany). Two hundred VP/VLBW and 197 term individuals were studied from birth to adulthood. Anxiety and mood disorders were assessed at 6, 8, and 26 years with standardized diagnostic interviews and social support via self-report at age 26. Results At age 6, VP/VLBW children were not at increased risk of any anxiety or mood disorder. At age 8, VP/VLBW more often had any anxiety disorder than term comparisons (11.8% vs. 6.6%, OR = 2.10, 95% CI [1.08–4.10]). VP/VLBW adults had an increased risk for any mood (27.5% vs. 18.8%, OR = 1.65 [1.02–2.67]) but not for any anxiety disorder (33.0% vs. 28.4%, OR = 1.27 [0.82–1.96]). None of the significant differences survived correction for multiple testing. Social support was associated with a lower risk of anxiety or mood disorders in both groups (OR = 0.81 [0.68–0.96]) and mediated the association of VP/VLBW birth with any anxiety or any mood disorders at age 26. Conclusions This study does not show a persistently increased risk for any anxiety or mood disorder after VP/VLBW birth. Low social support from a romantic partner mediates the risk for anxiety or mood disorders after VP/VLBW birth

Enabling precision medicine in neonatology, an integrated repository for preterm birth research.

Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of 'omics' data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes' Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of 'omics' datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research

Maternal Low-Level Lead Exposure and Fetal Growth

Background Limited epidemiologic studies have examined the association between maternal low-level lead exposure [blood lead (PbB) \u3c 10 μg/dL] and fetal growth. Objective We examined whether maternal low-level lead exposure is associated with decreased fetal growth. Methods We linked New York State Heavy Metals Registry records of women who had PbB measurements with birth certificates to identify 43,288 mother–infant pairs in upstate New York in a retrospective cohort study from 2003 through 2005. We used multiple linear regression with fractional polynomials and logistic regression to relate birth weight, preterm delivery, and small for gestational age to PbB levels, adjusting for potential confounders. We used a closed-test procedure to identify the best fractional polynomials for PbB among 44 combinations. Results We found a statistically significant association between PbB (square root transformed) and birth weight. Relative to 0 μg/dL, PbBs of 5 and 10 μg/dL were associated with an average of 61-g and 87-g decrease in birth weight, respectively. The adjusted odds ratio for PbBs between 3.1 and 9.9 μg/dL (highest quartile) was 1.04 [95% confidence interval (CI), 0.89–1.22] for preterm delivery and 1.07 (95% CI, 0.93–1.23) for small for gestational age, relative to PbBs ≤ 1 μg/dL (lowest quartile). No clear dose–response trends were evident when all of the quartiles were assessed. Conclusions Low-level PbB was associated with a small risk of decreased birth weight with a supralinear dose–response relationship, but was not related to preterm birth or small for gestational age. The results have important implications regarding maternal PbB

Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Investigating the feasibility of child mortality surveillance with postmortem tissue sampling: generating constructs and variables to strengthen validity and reliability in qualitative research

The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged &lt;5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS.Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting.Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability. These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS

Prediction of preterm delivery in symptomatic women using PAMG‐1, fetal fibronectin and phIGFBP‐1 tests: systematic review and meta‐analysis

Objective To assess the accuracy of placental alpha microglobulin‐1 (PAMG‐1), fetal fibronectin (fFN) and phosphorylated insulin‐like growth factor‐binding protein‐1 (phIGFBP‐1) tests in predicting spontaneous preterm birth (sPTB) within 7 days of testing in women with symptoms of preterm labor, through a systematic review and meta‐analysis of the literature. The test performance of each biomarker was also assessed according to pretest probability of sPTB ≤ 7 days. Methods The Cochrane, MEDLINE, PubMed and ResearchGate bibliographic databases were searched from inception until October 2017. Cohort studies that reported on the predictive accuracy of PAMG‐1, fFN and phIGFBP‐1 for the prediction of sPTB within 7 days of testing in women with symptoms of preterm labor were included. Summary receiver–operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive (LR+) and negative (LR–) likelihood ratios were generated using indirect methods for the calculation of pooled effect sizes with a bivariate linear mixed model for the logit of sensitivity and specificity, with each diagnostic test as a covariate, as described by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Results Bivariate mixed model pooled sensitivity of PAMG‐1, fFN and phIGFBP‐1 for the prediction of sPTB ≤ 7 days was 76% (95% CI, 57–89%), 58% (95% CI, 47–68%) and 93% (95% CI, 88–96%), respectively; pooled specificity was 97% (95% CI, 95–98%), 84% (95% CI, 81–87%) and 76% (95% CI, 70–80%) respectively; pooled PPV was 76.3% (95% CI, 69–84%) (P < 0.05), 34.1% (95% CI, 29–39%) and 35.2% (95% CI, 31–40%), respectively; pooled NPV was 96.6% (95% CI, 94–99%), 93.3% (95% CI, 92–95%) and 98.7% (95% CI, 98–99%), respectively; pooled LR+ was 22.51 (95% CI, 15.09–33.60) (P < 0.05), 3.63 (95% CI, 2.93–4.50) and 3.80 (95% CI, 3.11–4.66), respectively; and pooled LR– was 0.24 (95% CI, 0.12–0.48) (P < 0.05), 0.50 (95% CI, 0.39–0.64) and 0.09 (95% CI, 0.05–0.16), respectively. The areas under the ROC curves for PAMG‐1, fFN and phIGFBP‐1 for sPTB ≤ 7 days were 0.961, 0.874 and 0.801, respectively. Conclusions In the prediction of sPTB within 7 days of testing in women with signs and symptoms of PTL, the PPV of PAMG‐1 was significantly higher than that of phIGFBP‐1 or fFN. Other diagnostic accuracy measures did not differ between the three biomarker tests. As prevalence affects the predictive performance of a diagnostic test, use of a highly specific assay for a lower‐prevalence syndrome such as sPTB may optimize management