Variations in very preterm birth rates in 30 high-income countries: are valid international comparisons possible using routine data?

OBJECTIVE: Concerns about differences in registration practices across countries have limited the use of routine data for international very preterm birth (VPT) rate comparisons. DESIGN: Population-based study. SETTING: Twenty-seven European countries, the United States, Canada and Japan in 2010. POPULATION: A total of 9 376 252 singleton births. METHOD: We requested aggregated gestational age data on live births, stillbirths and terminations of pregnancy (TOP) before 32 weeks of gestation, and information on registration practices for these births. We compared VPT rates and assessed the impact of births at 22-23 weeks of gestation, and different criteria for inclusion of stillbirths and TOP on country rates and rankings. MAIN OUTCOME MEASURES: Singleton very preterm birth rate, defined as singleton stillbirths and live births before 32 completed weeks of gestation per 1000 total births, excluding TOP if identifiable in the data source. RESULTS: Rates varied from 5.7 to 15.7 per 1000 total births and 4.0 to 11.9 per 1000 live births. Country registration practices were related to percentage of births at 22-23 weeks of gestation (between 1% and 23% of very preterm births) and stillbirths (between 6% and 40% of very preterm births). After excluding births at 22-23 weeks, rate variations remained high and with a few exceptions, country rankings were unchanged. CONCLUSIONS: International comparisons of very preterm birth rates using routine data should exclude births at 22-23 weeks of gestation and terminations of pregnancy. The persistent large rate variations after these exclusions warrant continued surveillance of VPT rates at 24 weeks and over in high-income countries. TWEETABLE ABSTRACT: International comparisons of VPT rates should exclude births at 22-23 weeks of gestation and terminations of pregnancy.

Inter- and intraspecific comparisons of antiherbivore defenses in three species of rainforest understory shrubs.

Plants defend themselves against herbivores and pathogens with a suite of morphological, phenological, biochemical, and biotic defenses, each of which is presumably costly. The best studied are allocation costs that involve trade-offs in investment of resources to defense versus other plant functions. Decreases in growth or reproductive effort are the costs most often associated with antiherbivore defenses, but trade-offs among different defenses may also occur within a single plant species. We examined trade-offs among defenses in closely related tropical rain forest shrubs (Piper cenocladum, P. imperiale, and P. melanocladum) that possess different combinations of three types of defense: ant mutualists, secondary compounds, and leaf toughness. We also examined the effectiveness of different defenses and suites of defenses against the most abundant generalist and specialist Piper herbivores. For all species examined, leaf toughness was the most effective defense, with the toughest species, P. melanocladum, receiving the lowest incidence of total herbivory, and the least tough species, P. imperiale, receiving the highest incidence. Although variation in toughness within each species was substantial, there were no intraspecific relationships between toughness and herbivory. In other Piper studies, chemical and biotic defenses had strong intraspecific negative correlations with herbivory. A wide variety of defensive mechanisms was quantified in the three Piper species studied, ranging from low concentrations of chemical defenses in P. imperiale to a complex suite of defenses in P. cenocladum that includes ant mutualists, secondary metabolites, and moderate toughness. Ecological costs were evident for the array of defensive mechanisms within these Piper species, and the differences in defensive strategies among species may represent evolutionary trade-offs between costly defenses.

Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with a decreased number of D4Z4 repeats on chromosome 4q35. Diagnostic difficulties arise from atypical clinical presentations and from an overlap in D4Z4 numbers between controls and FSHD individuals. Thus, a molecular genetic test result with a borderline D4Z4 number has its limitations for the clinician wanting to differentiate between the diagnosis of FSHD and a myopathy presenting with FSHD-like symptoms.To investigate this problem in more detail we conducted a systematic study of 39 unrelated FSHD patients with borderline D4Z4 repeat numbers and 102 healthy controls. Our aim was threefold: [1] to define the molecular diagnostic cut-off point between FSHD cases and the control population, [2] to describe the myopathic spectrum in patients with borderline D4Z4 repeat numbers and [3] to look for correlations between D4Z4 number and clinical severity. The results indicate that there is no definite D4Z4 diagnostic cut-off point separating FSHD, FSHD-like myopathies and controls. A broad myopathic spectrum with four phenotypes (typical FSHD, facial-sparing FSHD, FSHD with atypical features, non-FSHD muscle disease) was found in the borderline region. The expected correlation of D4Z4 repeat number and clinical severity was not found. Therefore the molecular test is of limited help to differentiate FSHD from FSHDlike muscle disorders when the D4Z4 number is n = >or= 8.

Hyperoxia increases keratinocyte growth factor mRNA expression in neonatal rabbit lung.

Acute hyperoxic lung injury remains a major factor in the development of chronic lung disease in neonates. A critical step in the repair of acute lung injury is the proliferation of type II alveolar epithelial cells. Type II cell proliferation is stimulated by keratinocyte growth factor (KGF), an epithelial cell-specific mitogen. We sought to investigate KGF mRNA expression in relation to type II cell proliferation during hyperoxic lung injury. We studied a previously described newborn (NB) rabbit model of acute and chronic hyperoxic injury [C. T. D'Angio, J. N. Finkelstein, M. B. LoMonaco, A. Paxhia, S. A. Wright, R. B. Baggs, R. H. Notter, and R. M. Ryan. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L720-L730, 1997]. NB rabbits were placed in 100% O2 for 9 days and then recovered in 60% O2. RT-PCR was used to synthesize and amplify a 267-bp fragment of rabbit KGF cDNA from whole lung RNA. KGF mRNA expression was analyzed by ribonuclease protection assay, and mRNA abundance was quantified by phosphorimaging. Proliferating cell nuclear antigen immunohistochemistry was used on lung sections to identify proliferating cells. The rabbit partial cDNA sequenced was >95% homologous to human cDNA, and all amino acids were conserved. Whole lung KGF mRNA expression was increased 12-fold after 6 days of hyperoxia compared with control lungs, and remained increased throughout the 100% O2 exposure period. Proliferating cell nuclear antigen immunohistochemistry showed an increase in type II cell proliferation after 8-12 days of hyperoxia. NB rabbits exposed to hyperoxic injury exhibit increased whole lung KGF mRNA expression preceding type II cell proliferation. KGF may be an important mitogen in the regulation of alveolar epithelial repair after hyperoxic lung injury.

In vitro oral mucosa irritation testing with human cell cultures.

Cell cultures are a potentially useful model to predict in vivo oral mucosa irritation. To this end, oral mucosa organ equivalent cultures (OMOEC) and skin equivalent cultures (SEC), both derived from human tissue, were evaluated for their responsiveness to test dentifrices with graded degrees of irritation potential. OMOEC and SEC were treated with test dentifrices and responses were evaluated by histopathology, cell viability (MTT incorporation), and cytotoxicity [release of aspartate aminotransferase (AST)]. Cell viability in OMOEC and SEC was reduced in a dose- and time-dependent manner in response to the test dentifrices. Correspondingly, AST release was increased in a dose- and time-dependent manner in response to the test dentifrices. These results demonstrate that OMOEC and SEC systems respond linearly to graded degrees of irritation potential as represented by generic dentifrices. Such results in an in vitro model of oral mucosa irritation allow direct comparison of in vitro responses with those obtained in an in vivo model, thus providing the groundwork for a tiered approach to assessment of irritation potential of oral care products.

Coronary heart disease mortality risk: plasma insulin level is a more sensitive marker than hypertension or abnormal glucose tolerance in overweight males. The Paris Prospective Study.

The Paris Prospective Study I (7434 men) is a long-term investigation of cardiovascular diseases. A previous analysis has shown that high plasma insulin level was a more sensitive marker than glucose intolerance in the prediction of coronary heart disease (CHD). In order to ascertain the risk model for CHD in relation to high circulating plasma insulin level, we studied CHD mortality rates in groups of participants to the study with similar profiles of risk factors. The risk factors considered to cross-classify the subjects were: serum cholesterol level, blood pressure, fasting plasma insulin level (all the significant predictors of CHD mortality in the Cox regression model), plus body mass index (BMI) and 2-h post-load blood glucose level. Serum cholesterol level was linearly related to CHD mortality risk. The strength of the association of blood pressure to the risk was reduced when BMI increased. By contrast, the association of blood pressure to the risk remained linear when plasma insulin level rather than BMI was considered. Plasma insulin level was a more sensitive marker of CHD risk than glucose intolerance in the overweight group. Moreover, in this group, the relation to CHD mortality risk was stronger for plasma insulin level than for blood pressure.

A comparison of cesarean section morbidity in urban and rural hospitals. A three-year retrospective review of 1,177 charts.

To determine whether there was a significant difference in morbidity rates from cesarean section between urban and rural hospitals, we reviewed 742 maternal records from three urban hospitals and 435 records from 11 rural hospitals, along with the corresponding infant charts. When a comparison was made of advance in diet, day of discharge, elevations of temperature, number of positive cultures, use of two or more antibiotics, use of blood transfusions, and incidence of major complications, significant differences were found only in the number of positive cultures and use of antibiotics, which occurred more frequently in rural hospitals. Pediatric morbidity was evaluated by comparing Apgar scores, temperatures less than 36 degrees C, use of oxygen for longer than 15 minutes, number of infants intubated, use of intravenous fluids and antibiotics, incidence of respiratory distress syndrome and transient tachypnea, number of neonatal transfers, and major complications. Urban hospitals had significantly more Apgar scores of 4 to 6 at 5 minutes (p less than 0.01). Temperatures less than 36 degrees C were found more frequently in rural hospitals (p less than 0.001). No statistical difference was found in any other category. The results show little difference in maternal or pediatric morbidity rates between urban and rural hospitals and between obstetricians and family practitioners.

Malignant schwannoma: report of a case mimicking lumbar disk disease.

Primary neurogenic retroperitoneal tumors in the adult are rare. This case presentation reviews an unusual history of a patient who presented with pain and neurologic deficits suggesting lumbar disk disease but who was unrelieved by laminectomy and disk removal. Later he was found to have a malignant schwannoma arising from the right L nerve root. Experience such as this reminds physicians that when the result of treatment is not as expected the original diagnosis must be questioned.