Project description:The multidisciplinary nature and long duration of birth cohort studies allow investigation of the relationship between general and oral health and indicate the most appropriate stages in life to intervene. To date, the worldwide distribution of oral health-related birth cohort studies (OHRBCSs) has not been mapped, and a synthesis of information on methodological characteristics and outcomes is not available. We mapped published literature on OHRBCSs, describing their oral health-related data and methodological aspects. A 3-step search strategy was adopted to identify published studies using PubMed, Embase, Web of Science, and OVID databases. Studies with baseline data collection during pregnancy or within the first year of life or linked future oral health data to exposures during either of these 2 life stages were included. Studies examining only mothers' oral health and specific populations were excluded. In total, 1,721 articles were suitable for initial screening of titles and abstracts, and 528 articles were included in the review, identifying 120 unique OHRBCSs from 34 countries in all continents. The review comprised literature from the mid-1940s to the 21st century. Fifty-four percent of the OHRBCSs started from 2000 onward, and 75% of the cohorts were from high-income and only 2 from low-income countries. The participation rate between the baseline and the last oral health follow-up varied between 7% and 93%. Ten cohorts that included interventions were mostly from 2000 and with fewer than 1,000 participants. Seven data-linkage cohorts focused mostly on upstream characteristics and biological aspects. The most frequent clinical assessment was dental caries, widely presented as decayed, missing, and filled teeth (DMFT/dmft). Periodontal conditions were primarily applied as isolated outcomes or as part of a classification system. Socioeconomic classification, ethnicity, and country- or language-specific assessment tools varied across countries. Harmonizing definitions will allow combining data from different studies, adding considerable strength to data analyses; this will be facilitated by forming a global consortium.

Project description:Epidemiological studies investigating associations between early life factors and adult health are often limited to studying exposures that can be reliably recalled in adulthood or obtained from existing medical records. There are few US studies with detailed data on the pre- and postnatal environment whose study populations are now in adulthood; one exception is the Collaborative Perinatal Project (CPP). We contacted former female participants of the New York site of the CPP who were born from 1959 to 1963 and were prospectively followed for 7 years to examine whether the pre- and postnatal environment is associated with adult health in women 40 years after birth. The New York CPP cohort is particularly diverse; at enrolment, the race/ethnicity distribution of mothers was approximately 30% White, 40% Black and 30% Puerto Rican. Of the 841 eligible women, we successfully traced 375 women (45%) and enrolled 262 women (70% of those traced). Baseline data were available for all eligible women, and we compared those who participated with the remaining cohort (n = 579). Higher family socio-economic status at age 7, availability of maternal social security number, and White race/ethnicity were statistically significantly associated with a higher probability of tracing. Of those traced, race/ethnicity was associated with participation, with Blacks and Puerto Ricans less likely to participate than Whites (OR = 0.5, 95% CI 0.3, 0.8, and OR = 0.5, 95% CI 0.3, 1.0, respectively). In addition, higher weight at 7 years was associated with lower participation (OR = 0.95, 95% CI 0.92, 0.99), but this association was observed only among the non-White participants. None of the other maternal characteristics, infant or early childhood growth measures was associated with participation or with tracing, either overall or within each racial/ethnic subgroup. Daughters' recall of early life factors such as pre-eclampsia (sensitivity = 24%) and birthweight were generally poor, with the latter varying by category of birthweight with the highest sensitivity for the largest babies (81%) and the lowest sensitivity for the smallest babies (54%). These data reinforce the need to rejuvenate existing birth cohorts with prospective data for life course studies of adult health. Understanding the factors that are associated with tracing and participation in these existing cohorts will help in interpreting the validity and generalisability of the findings from these invaluable cohorts.

Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.

Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates. 36 Umbilical cord blood samples were collected in EDTA tubes soon after placental delivery. Blood samples were centrifuged at 3,000 RPM to separate plasma, and buffy coats were aliquoted and stored at -80oC. DNA was extracted using the DNeasy Kit (Qiagen). DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina).

Project description:Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of "safer" antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative "superbugs," every effort must be made to improve the clinical utility of the last-line polymyxins. SIGNIFICANCE STATEMENT: Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.

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Oral Health Birth Cohort Studies: Achievements, Challenges, and Potential.

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