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JAMA Network Open Dec 2023Preterm birth is a leading cause of preventable neonatal morbidity and mortality. Preterm birth rates at the national level may mask important geographic variation in...
IMPORTANCE
Preterm birth is a leading cause of preventable neonatal morbidity and mortality. Preterm birth rates at the national level may mask important geographic variation in rates and trends at the county level.
OBJECTIVE
To estimate age-standardized preterm birth rates by US county from 2007 to 2019.
DESIGN, SETTING, AND PARTICIPANTS
This serial cross-sectional study used data from the National Center for Health Statistics composed of all live births in the US between 2007 and 2019. Data analyses were performed between March 22, 2022, and September 29, 2022.
MAIN OUTCOMES AND MEASURES
Age-standardized preterm birth (<37 weeks' gestation) and secondarily early preterm birth (<34 weeks' gestation) rates by county and year calculated with a validated small area estimation model (hierarchical bayesian spatiotemporal model) and percent change in preterm birth rates using log-linear regression models.
RESULTS
Between 2007 and 2019, there were 51 044 482 live births in 2383 counties. In 2007, the national age-standardized preterm birth rate was 12.6 (95% CI, 12.6-12.7) per 100 live births. Preterm birth rates varied significantly among counties, with an absolute difference between the 90th and 10th percentile counties of 6.4 (95% CI, 6.2-6.7). The gap between the highest and lowest counties for preterm births was 20.7 per 100 live births in 2007. Several counties in the Southeast consistently had the highest preterm birth rates compared with counties in California and New England, which had the lowest preterm birth rates. Although there was no statistically significant change in preterm birth rates between 2007 and 2019 at the national level (percent change, -5.0%; 95% CI, -10.7% to 0.9%), increases occurred in 15.4% (95% CI, 14.1%-16.9%) of counties. The absolute and relative geographic inequalities were similar across all maternal age groups. Higher quartile of the Social Vulnerability Index was associated with higher preterm birth rates (quartile 4 vs quartile 1 risk ratio, 1.34; 95% CI, 1.31-1.36), which persisted across the study period. Similar patterns were observed for early preterm birth rates.
CONCLUSIONS AND RELEVANCE
In this serial cross-sectional study of county-level preterm and early preterm birth rates, substantial geographic disparities were observed, which were associated with place-based social disadvantage. Stability in aggregated rates of preterm birth at the national level masked increases in nearly 1 in 6 counties between 2007 and 2019.
Topics: Female; Humans; Infant, Newborn; Infant; Premature Birth; Cross-Sectional Studies; Bayes Theorem; New England
PubMed: 38064212
DOI: 10.1001/jamanetworkopen.2023.46864 -
The Lancet. Planetary Health Feb 2024Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological...
BACKGROUND
Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs.
METHODS
In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery.
FINDINGS
We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion).
INTERPRETATION
In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class.
FUNDING
National Institutes of Health.
Topics: United States; Pregnancy; Female; Humans; Infant, Newborn; Premature Birth; Birth Weight; Diethylhexyl Phthalate; Pregnancy Complications; Phthalic Acids
PubMed: 38331533
DOI: 10.1016/S2542-5196(23)00270-X -
Statistics in Medicine Aug 2023Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities... (Review)
Review
Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities and clinics. Despite advances in the design and analysis of CRTs, several challenges remain. First, there are many possible ways to specify the causal effect of interest (eg, at the individual-level or at the cluster-level). Second, the theoretical and practical performance of common methods for CRT analysis remain poorly understood. Here, we present a general framework to formally define an array of causal effects in terms of summary measures of counterfactual outcomes. Next, we provide a comprehensive overview of CRT estimators, including the t-test, generalized estimating equations (GEE), augmented-GEE, and targeted maximum likelihood estimation (TMLE). Using finite sample simulations, we illustrate the practical performance of these estimators for different causal effects and when, as commonly occurs, there are limited numbers of clusters of different sizes. Finally, our application to data from the Preterm Birth Initiative (PTBi) study demonstrates the real-world impact of varying cluster sizes and targeting effects at the cluster-level or at the individual-level. Specifically, the relative effect of the PTBi intervention was 0.81 at the cluster-level, corresponding to a 19% reduction in outcome incidence, and was 0.66 at the individual-level, corresponding to a 34% reduction in outcome risk. Given its flexibility to estimate a variety of user-specified effects and ability to adaptively adjust for covariates for precision gains while maintaining Type-I error control, we conclude TMLE is a promising tool for CRT analysis.
Topics: Infant, Newborn; Female; Humans; Computer Simulation; Premature Birth; Randomized Controlled Trials as Topic; Sample Size; Causality; Cluster Analysis
PubMed: 37308115
DOI: 10.1002/sim.9813 -
International Journal of Molecular... Sep 2023The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal...
The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal and immunological modifications. Moreover, dysbiosis during pregnancy has been associated with preterm birth, which is influenced by factors such as cervical shortening, infection, inflammation, and oxidative stress. However, dysbiosis also affects the levels of lipopolysaccharide-binding protein (LBP), short-chain fatty acids (SCFAs), and free fatty acids (FFA) in other tissues and the bloodstream. In this study, we investigated the plasmatic levels of some pro-inflammatory cytokines, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), heat shock protein 70 (Hsp70), and microbial markers in pregnant women with a short cervix (≤25 mm) compared to those with normal cervical length (>25 mm). We examined the differences in the concentration of these markers between the two groups, also assessing the impact of gestational diabetes mellitus. Understanding the relationship between GM dysbiosis, inflammatory mediators, and cervical changes during pregnancy may contribute to the identification of potential biomarkers and therapeutic targets for the prevention and management of adverse pregnancy outcomes, including preterm birth.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Diabetes, Gestational; Gastrointestinal Microbiome; Pregnant Women; Cervix Uteri; Dysbiosis; Premature Birth
PubMed: 37686463
DOI: 10.3390/ijms241713653 -
Nature Neuroscience Jan 2024The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap,...
The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations.
Topics: Male; Female; Humans; Infant, Newborn; Child, Preschool; Child; Premature Birth; Cognition; Brain; Neuroimaging; Magnetic Resonance Imaging
PubMed: 37996530
DOI: 10.1038/s41593-023-01501-6 -
BMC Pregnancy and Childbirth Jul 2023There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product...
BACKGROUND
There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.
METHODS
Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.
RESULTS
The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.
CONCLUSIONS
This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.
Topics: Infant, Newborn; Female; Humans; Premature Birth; Progesterone; Obstetric Labor, Premature; Fatty Acids, Omega-3
PubMed: 37464260
DOI: 10.1186/s12884-023-05842-9 -
Pediatric Research Oct 2023This study is a preliminary clinical investigation with the objective to evaluate the facial thermal response of premature and term neonates to a non-painful stressor...
BACKGROUND
This study is a preliminary clinical investigation with the objective to evaluate the facial thermal response of premature and term neonates to a non-painful stressor (hunger) using infrared thermography (IRT). The development of objective and reliable parameters to monitor pain and stress is of relevance for optimal neonatal outcome and achieving a better management of patient comfort.
METHODS
We enrolled 12 neonates ranging from 27 to 39 weeks gestation (median: 34) and aged 3-79 days (median: 13). Recordings were performed before and after feeding, with and without hunger. Six regions of interest were chosen for evaluation (nose tip, periorbital and corrugator region, forehead, perioral and chin region).
RESULTS
There was an increase in the facial temperature in infants immediately prior to their next feed relative to infants who were not hungry, with the nasal tip being the facial evaluation site with the greatest temperature change.
CONCLUSIONS
The IRT appears to be a feasible and suitable method to detect changes in the neonatal patient. The thermal variations observed seem to reflect an arousal mediated by the parasympathetic nervous system, which has been described in existing infant stress research.
IMPACT
This is the first study to examine the use of infrared thermography (IRT) in monitoring the facial thermal response to a mild stressor (hunger) in premature and term neonates. Hunger as a mild, non-pain-associated stressor showed a significant effect on the facial temperature. The thermal signature of the regions of interest chosen showed hunger-related thermal variations. Results suggest the feasibility and suitability of IRT as an objective diagnostic tool to approach stress and changes in the condition of the neonatal patient.
Topics: Infant, Newborn; Infant; Female; Humans; Pain; Face; Premature Birth; Gestational Age; Nose
PubMed: 37161075
DOI: 10.1038/s41390-023-02614-1 -
Biology of Sex Differences Jul 2023Premature birth and/or low birthweight have long-lasting effects on cognition. The purpose of the present systematic review is to examine whether the effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premature birth and/or low birthweight have long-lasting effects on cognition. The purpose of the present systematic review is to examine whether the effects of prematurity and/or low birth weight on neurodevelopmental outcomes differ between males and females.
METHODS
Web of Science, Scopus, and Ovid MEDLINE were searched for studies of humans born premature and/or of low birthweight, where neurodevelopmental phenotypes were measured at 1 year of age or older. Studies must have reported outcomes in such a way that it was possible to assess whether effects were greater in one sex than the other. Risk of bias was assessed using both the Newcastle-Ottawa scale and the National Institutes of Health Quality assessment tool for observational cohort and cross-sectional studies.
RESULTS
Seventy-five studies were included for descriptive synthesis, although only 24 presented data in a way that could be extracted for meta-analyses. Meta-analyses found that severe and moderate prematurity/low birthweight impaired cognitive function, and severe prematurity/low birthweight also increased internalizing problem scores. Moderate, but not severe, prematurity/low birthweight significantly increased externalizing problem scores. In no case did effects of prematurity/low birthweight differ between males and females. Heterogeneity among studies was generally high and significant, although age at assessment was not a significant moderator of effect. Descriptive synthesis did not identify an obvious excess or deficiency of male-biased or female-biased effects for any trait category. Individual study quality was generally good, and we found no evidence of publication bias.
CONCLUSIONS
We found no evidence that the sexes differ in their susceptibility to the effects of severe or moderate prematurity/low birthweight on cognitive function, internalizing traits or externalizing traits. Result heterogeneity tended to be high, but this reflects that one sex is not consistently more affected than the other. Frequently stated generalizations that one sex is more susceptible to prenatal adversity should be re-evaluated.
Topics: United States; Pregnancy; Female; Male; Humans; Infant, Newborn; Premature Birth; Sex Characteristics; Birth Weight; Cross-Sectional Studies; Infant, Low Birth Weight
PubMed: 37434174
DOI: 10.1186/s13293-023-00532-9 -
Nature Communications Sep 2023White matter connectivity supports diverse cognitive demands by efficiently constraining dynamic brain activity. This efficiency can be inferred from network...
White matter connectivity supports diverse cognitive demands by efficiently constraining dynamic brain activity. This efficiency can be inferred from network controllability, which represents the ease with which the brain moves between distinct mental states based on white matter connectivity. However, it remains unclear how brain networks support diverse functions at birth, a time of rapid changes in connectivity. Here, we investigate the development of network controllability during the perinatal period and the effect of preterm birth in 521 neonates. We provide evidence that elements of controllability are exhibited in the infant's brain as early as the third trimester and develop rapidly across the perinatal period. Preterm birth disrupts the development of brain networks and altered the energy required to drive state transitions at different levels. In addition, controllability at birth is associated with cognitive ability at 18 months. Our results suggest network controllability develops rapidly during the perinatal period to support cognitive demands but could be altered by environmental impacts like preterm birth.
Topics: Infant, Newborn; Infant; Female; Pregnancy; Humans; Connectome; Premature Birth; Brain; White Matter; Cognition
PubMed: 37726267
DOI: 10.1038/s41467-023-41499-w -
The Journal of Maternal-fetal &... Dec 2023Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract. (Observational Study)
Observational Study
BACKGROUND
Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract.
OBJECTIVES
To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates.
METHODS
Prospective observational cohort study recruiting EP singleton pregnancies (gestational age at birth ≤28 weeks) with confirmed HCA. FIR was defined by fetal neutrophils in the chorionic vessels and/or umbilical vessels. Positive culture was defined as growth of potentially pathogenic bacteria in a sample from the cervicovaginal tract prior to birth, or if a cervicovaginal culture was lacking, a culture result from the placenta was used. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between FIR, a positive culture result and adverse outcomes, defined as bronchopulmonary dysplasia (BPD), brain pathology assessed by magnetic resonance imaging, retinopathy of prematurity, necrotizing enterocolitis, early-onset neonatal sepsis, and perinatal death. A composite outcome variable included one or more adverse outcomes.
RESULTS
We included 71 cases with HCA, of which 51 (72%) had FIR. Maternal age, rate of clinical chorioamnionitis (CCA), preterm pre-labor rupture of membranes (PPROM), the number of women receiving antenatal steroids and antibiotics, and the rate of positive maternal cultures of potentially pathogenic bacteria were all significantly higher in the HCA with FIR. Neonates in the FIR group had significantly higher levels of blood leukocytes compared to those without. FIR was associated with a longer interval from PPROM to delivery (log-rank test: = .022). Microbiological sampling had been performed in 63 (89%) cases, of which 60 (95%) were cervicovaginal samples. No associations were found between a positive culture and adverse neonatal outcomes, in contrast to FIR, that was significantly associated to BPD and brain pathology.
CONCLUSIONS
In a cohort of EP pregnancies with confirmed HCA, the presence of FIR was associated with advanced maternal age, CCA, PPROM, antenatal steroids and antibiotics, and a positive maternal culture of potentially pathogenic bacteria. However, the presence of FIR, and not a positive culture, was associated with adverse neonatal outcomes.
Topics: Infant, Newborn; Female; Infant; Pregnancy; Humans; Chorioamnionitis; Infant, Extremely Premature; Prospective Studies; Premature Birth; Fetal Membranes, Premature Rupture; Gestational Age; Infant, Newborn, Diseases; Bronchopulmonary Dysplasia
PubMed: 37031964
DOI: 10.1080/14767058.2023.2196599