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BackgroundPhthalates 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.MethodsIn 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.FindingsWe 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 log10 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).InterpretationIn 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.FundingNational Institutes of Health.

For a variety of reasons, the definition and the classification of cerebral palsy (CP) need to be reconsidered. Modern brain imaging techniques have shed new light on the nature of the underlying brain injury and studies on the neurobiology of and pathology associated with brain development have further explored etiologic mechanisms. It is now recognized that assessing the extent of activity restriction is part of CP evaluation and that people without activity restriction should not be included in the CP rubric. Also, previous definitions have not given sufficient prominence to the non-motor neurodevelopmental disabilities of performance and behaviour that commonly accompany CP, nor to the progression of musculoskeletal difficulties that often occurs with advancing age. In order to explore this information, pertinent material was reviewed on July 11-13, 2004 at an international workshop in Bethesda, MD (USA) organized by an Executive Committee and participated in by selected leaders in the preclinical and clinical sciences. At the workshop, it was agreed that the concept 'cerebral palsy' should be retained. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, health officials, families and the public and would provide a common language for improved communication. Panels organized by the Executive Committee used this information and additional comments from the international community to generate a report on the Definition and Classification of Cerebral Palsy, April 2006. The Executive Committee presents this report with the intent of providing a common conceptualization of CP for use by a broad international audience. [ABSTRACT FROM AUTHOR]

The reliability of classification of cerebral palsy (CP) in low-birthweight children was assessed by using clinical and research study records sampled from population-based cohort studies in the USA, The Netherlands, Canada, and Germany. Records of neurological examination findings and functional motor assessments were submitted to up to five pediatricians with expertise in CP diagnosis, who grouped children into categories referred to as 'disabling' CP, 'non-disabling' CP, and no CP. Each study provided between 31 and 51 records of children assessed between 2 and 8 years of age, approximately equally divided among the three groupings. The discrimination between 'any CP' and 'no CP' was only fair (mean Kappa coefficients 0.37 to 0.69). However, when more detailed information describing motor function was used, children with 'disabling' CP could be distinguished, on the basis of records, from those without CP or with 'non-disabling' CP with good to excellent reliability (mean Kappa coefficients 0.69 to 0.88). Because of the substantially higher agreement observed when these functional distinctions are made, we recommend that reports or comparisons of rates of CP should include levels of motor function of children with CP, and not simply total CP, among the outcomes of interest. [ABSTRACT FROM AUTHOR]

Contemporaneous with John Snow's famous study of the 1854 London cholera epidemic were 2 other investigations: a local study of the Broad Street outbreak and an investigation of the entire epidemic, undertaken by England's General Board of Health. More than a quarter-century prior to Koch's description of Vibrio comma, a Board of Health investigator saw microscopic 'vibriones' in the rice-water stools of cholera patients that, in his later life, he concluded had been cholera bacilli. Although this finding was potential evidence for Snow's view that cholera was due to a contagious and probably live agent transmitted in the water supply, the Board of Health rejected Snow's conclusions. The Board of Health amassed a huge amount of information which it interpreted as supportive of its conclusion that the epidemic was attributable not so much to water as to air. Snow, by contrast, systematically tested his hypothesis that cholera was water-borne by exploring evidence that at first glance ran contrary to his expectations. Snow's success provides support for using a hypothetico-deductive approach in epidemiology, based on tightly focused hypotheses strongly grounded in pathophysiology. [ABSTRACT FROM AUTHOR]

During October and November 1977, eight newborns with critical congenital heart disease, six of these with left sided lesions, were admitted to a New Jersey newborn unit serving two predominantly rural counties with 9700 annual live births. The six left heart lesions (three cases of hypoplastic left heart, two of interrupted aortic arch, and one of aortic coarctation) represented 30% of all neonatal left sided lesions seen at the unit in the three year period 1976-8. The scan statistic for temporal clustering was significant (p less than 0.05). A case-control study was performed in which an average of four controls were matched to each case. A questionnaire was administered to the mothers of cases and controls concerning occupation, periconceptional and prenatal nutrition, radiation and chemical exposure, use of alcohol and tobacco, medications, immunisations, infections, and other exposures. No statistically significant differences between cases and controls were found on any of these items. Although no aetiology for this cluster of congenital heart anomalies could be found, it is of interest that three temporal clusters of fetuses or newborns with chromosomal trisomies have been reported in the medical literature whose conceptions were roughly contemporaneous with those of the infants in our series. These occurred in Rhode Island/Massachusetts, Maryland, and New York City. A speculative possibility is that these four point epidemics represented exposure to a common teratogenic agent, perhaps influenza B, in the winter of 1976/77 in the northeastern United States. [ABSTRACT FROM PUBLISHER]