Evaluation of identifier field agreement in linked neonatal records.

OBJECTIVE: To better address barriers arising from missing and unreliable identifiers in neonatal medical records, we evaluated agreement and discordance among traditional and non-traditional linkage fields within a linked neonatal data set. STUDY DESIGN: The retrospective, descriptive analysis represents infants born from 2013 to 2015. We linked children's hospital neonatal physician billing records to newborn medical records originating from an academic delivery hospital and evaluated rates of agreement, discordance and missingness for a set of 12 identifier field pairs used in the linkage algorithm. RESULTS: We linked 7293 of 7404 physician billing records (98.5%), all of which were deemed valid upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non-matching identifier pairs. Only 4.8% had complete agreement among all 12 identifier pairs. CONCLUSION: Our approach to selection of linkage variables and data formatting preparatory to linkage have generalizability, which may inform future neonatal and perinatal record linkage efforts.

Home visiting for first-time mothers and subsequent pregnancy spacing.

OBJECTIVE: The objective of the study was to determine the association of home visiting with subsequent pregnancy outcomes. STUDY DESIGN: Retrospective study of Ohio mothers delivering their first infant from 2007 to 2009. First, we compared mothers enrolled in home visiting with a matched eligible group. Second, we compared outcomes within home visiting based on program participation (low <25% of recommended home visits, moderate 25 to 75%, high 75 to 100% and very high >100%). Time to subsequent pregnancy within 18 months was evaluated using Cox proportional hazards regression; logistic regression tested the likelihood of subsequent preterm birth. RESULTS: Of 1516 participants, 1460 were matched 1:1 to a comparison mother (n=2920). After multivariable adjustment, enrollment was associated with no difference in pregnancy spacing or subsequent preterm birth. Among those enrolled, moderate vs low participants had reduced risk of repeat pregnancy over 18 months (hazard ratio 0.68, P=0.003). CONCLUSION: Increased pregnancy spacing is observed among women with at least moderate home visiting participation.

Estimating community-level costs of preterm birth.

OBJECTIVES: To develop generalizable methods for estimating the economic impact of preterm birth at the community level on initial hospital expenditures, educational attainment and lost earnings as well as to estimate potential savings associated with reductions in preterm birth. STUDY DESIGN: The retrospective, population-based analysis used vital statistics and population demographics from Hamilton County, Ohio, USA, in 2012. METHODS: We adjusted previously reported, mean initial hospital cost estimates (stratified by each week of gestation) to 2012 dollars using national cost-to-charge ratios. Next, we calculated excess costs attributable to prematurity and potential hospital cost savings, which could be realized by prolonging each preterm pregnancy by a single week of gestation. Using reported associations among preterm birth, educational attainment and adult earnings, we developed generalizable formulas to calculate lost academic degrees and lost income estimates attributable to preterm birth. The formulas generated estimates based on local population demographics. RESULTS: The annual initial hospital cost associated with 1444 preterm infants was estimated at $93 million. In addition, over 9000 fewer college degrees and over $300 million in lost annual earnings were attributed to local adults who were born preterm. Prolonging each preterm birth by 1 week could potentially reduce initial hospital expenditures by over $25 million. Additional potential savings could be realized as healthier infants attain higher levels of education and earnings as adults. CONCLUSIONS: The generalizable methods developed for estimating the economic impact of preterm birth at the community level can be used by any community in which vital statistics and population demographics are available. Cost estimates can serve to rally support for local stakeholder investment in developing strategies for preterm birth intervention leading to improved pregnancy outcomes.

Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

OBJECTIVE: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. STUDY DESIGN: The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. RESULTS: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. CONCLUSION: Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

A population study of first and subsequent pregnancy smoking behaviors in Ohio.

OBJECTIVE: The objective of this study is to identify maternal characteristics associated with non-smoking during a subsequent pregnancy after first pregnancy smoking. STUDY DESIGN: We conducted a retrospective population-based analysis of Ohio vital birth records from 2007 to 2013. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for detection of characteristics associated with non-smoking during a subsequent pregnancy after first pregnancy smoking. RESULTS: Among 75 190 mothers, 75.6% were non-smokers and 13.7% were smokers during both pregnancies. During their first pregnancy, 49.7% of 15 075 smokers quit. Of them, 50.1% remained non-smokers during their subsequent pregnancy. Women who reduced, but continued smoking during their first pregnancy, were more than five times as likely to smoke during their subsequent pregnancy than women who quit (odds ratio (95% confidence interval): 2.85 (2.43 to 3.35) vs 0.55 (0.45 to 0.67)). CONCLUSION: Interventions targeting complete cessation, rather than reduction in smoking among first-time mothers, may be the most effective at optimizing long-term health benefits.

VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice.

To determine whether increased levels of VEGF disrupt postnatal lung formation or function, conditional transgenic mice in which VEGF 164 expression was enhanced in respiratory epithelial cells were produced. VEGF expression was induced in the lungs of VEGF transgenic pups with doxycycline from postnatal day 1 through 2 and 6 wk of age. VEGF levels were higher in bronchoalveolar lavage fluid (BALF) and lung homogenates of VEGF transgenic mice compared with endogenous VEGF levels in controls. Neonatal mortality was increased by 50% in VEGF transgenic mice. Total protein content in BALF was elevated in VEGF transgenic mice. Surfactant protein B protein expression was unaltered in VEGF transgenic mice. Although postnatal alveolar and vascular development were not disrupted by VEGF expression, VEGF transgenic mice developed pulmonary hemorrhage, alveolar remodeling, and macrophage accumulation as early as 2 wk of age. Electron microscopy demonstrated abnormal alveolar capillary endothelium in the VEGF transgenic mice. In many locations, the endothelium was discontinuous with segments of attenuated endothelial cells. Large numbers of hemosiderin-laden macrophages and varying degrees of emphysema were observed in adult VEGF transgenic mice. Overexpression of VEGF in the neonatal lung increased infant mortality and caused pulmonary hemorrhage, hemosiderosis, alveolar remodeling, and inflammation.

Amino acids from ultraviolet irradiation of interstellar ice analogues.

Amino acids are the essential molecular components of living organisms on Earth, but the proposed mechanisms for their spontaneous generation have been unable to account for their presence in Earth's early history. The delivery of extraterrestrial organic compounds has been proposed as an alternative to generation on Earth, and some amino acids have been found in several meteorites. Here we report the detection of amino acids in the room-temperature residue of an interstellar ice analogue that was ultraviolet-irradiated in a high vacuum at 12 K. We identified 16 amino acids; the chiral ones showed enantiomeric separation. Some of the identified amino acids are also found in meteorites. Our results demonstrate that the spontaneous generation of amino acids in the interstellar medium is possible, supporting the suggestion that prebiotic molecules could have been delivered to the early Earth by cometary dust, meteorites or interplanetary dust particles.

Simulated cometary matter as a test for enantiomer separating chromatography for use on comet 46P/Wirtanen.

The Cometary Sampling and Composition Experiment on board of European Space Agency's cornerstone mission ROSETTA is designed to identify organic molecules in cometary matter in situ by a combined pyrolysis gas chromatographic and mass spectrometric technique. Its capillary columns coated with chiral stationary phases received considerable attention, because they are designed for separations of non-complex enantiomers to allow the determination of enantiomeric ratios of cometary chiral organic compounds and consequently to provide information about the origin of molecular parity violation in biomolecules. To get gas chromatographic access to organic compounds on the comet, where macromolecules and complex organic polymers of low volatility are expected to make up the main organic ingredients, the combination of two injection techniques will be applied. The pyrolysis technique performed by heating cometary samples stepwise to defined temperatures in specific ovens resulting in thermochemolysis reactions of polymers and a chemical derivatization technique, in which the reagent dimethylformamide dimethylacetal assists pyrolysis derivatization reactions in producing methyl esters of polar monomers. The combination of the reagent assisted pyrolysis gas chromatographic technique with enantiomer separating chromatography was tested with laboratory-produced simulated cometary matter.

A feeding protocol for healthy preterm infants that shortens time to oral feeding.

OBJECTIVE: To test the hypothesis that healthy preterm infants randomly assigned to a semi-demand feeding protocol would require fewer days to attain oral feeding and have a satisfactory weight gain compared with control infants receiving standard care. STUDY DESIGN: In 2 neonatal intensive care nurseries, 81 infants 32 to < or = 34 weeks' postconceptional age were randomly assigned to the control (n = 41) or experimental (n = 40) protocol for transition from gavage to oral feedings. The control protocol followed the standard practice of gradually increasing scheduled oral feedings, whereas the experimental protocol used a semi-demand feeding method contingent on infant behavior. Analysis of variance techniques were used to compare the study groups for number of days to attain oral feeding and weight gain. RESULTS: The semi-demand method shortened the time for infants to achieve oral feeding by 5 days (P < .001). There were no differences in weight gain between the study groups, and both groups had satisfactory weight gain. CONCLUSION: The semi-demand method for the transition from gavage to oral feeding in healthy, preterm infants 32 to < or = 34 weeks postconceptional age promotes faster attainment of oral feeding and does not compromise their weight gain.

In vitro model for developmental progression from vasculogenesis to angiogenesis with a murine endothelial precursor cell line, MFLM-4.

In the embryo, vascular networks are developed through both vasculogenesis, the assembly of vessels from endothelial progenitor cells or hemangioblasts, and angiogenesis, the sprouting of vessels from preexisting capillaries. Cell culture models using endothelial cells (EC) and various extracellular matrix components have been useful in understanding the cellular and molecular factors involved in angiogenesis. However, there are few models of vasculogenesis. Using a murine endothelial precursor cell line, MFLM-4, derived from e14.5 lung mesenchyme, we have developed a culture system that not only recapitulates many of the characteristics of vasculogenesis but also progresses into angiogenesis. By 8 h, MFLM-4 cultured on the basement membrane preparation Matrigel invade the matrix, coalesce, and assemble into large clusters of cells resembling blood islands. During vascular development, blood islands are the focal areas for coalescence of endothelial precursors. For MFLM-4, this phase of in vitro vasculogenic clustering does not require proliferation. If proliferation is not blocked, MFLM-4 progresses into an angiogenic phase with the clusters forming multicell angiogenic sprouts. Through 3 days of culture, lumens form within the clusters, adjacent clusters are connected with tube-like structures, and eventually an extensive network or plexus of clusters connected by capillary-like tubes is formed. MFLM-4 cultured on Matrigel provides an in vitro system for analysis of the multistage, concurrent processes of vasculogenesis and angiogenesis.

Embryonic vasculogenesis by endothelial precursor cells derived from lung mesenchyme.

During development, the lung mesenchyme has a dynamic relationship with the branching airway. Embryonic lung mesenchyme is loosely packed and composed of indistinguishable cells, yet it is the source of vascular progenitors that will become endothelial cells, smooth muscle cells and fibroblasts. In the lung, vessel development in the periphery proceeds first through vasculogenesis, the migration and assembly of cells into a primitive network, and subsequently, through angiogenesis, the sprouting of vessels from this network. As a way to assess the cellular and molecular mechanisms of lung vascularization, we have isolated and cloned cell lines from mouse fetal lung mesenchyme (MFLM). Two of these MFLM cell lines, MFLM-4 and MFLM-91U, display characteristics of an endothelial lineage. RNA analysis demonstrates transcripts for the vascular endothelial growth factor receptors R1 and R2, the receptor tyrosine kinases, Tie-1 and Tie-2, as well as the Tie-2 ligands, Ang-1 and -2. The MFLM cell lines form extensive networks of capillary-like structures with lumens when cultured on a reconstituted basement membrane. In vivo, following blastocyst injection, the MFLM cells chimerize endothelium of the lung and areas of the heart vasculature. The results from these studies suggest that MFLM-4 and MFLM-91U, derived from embryonic lung mesenchyme, can function in vitro and in vivo as endothelial precursors and as models of cardiopulmonary vascularization. Dev Dyn 2000;217:11-23.

The extraterrestrial origin of the homochirality of biomolecules--rebuttal to a critique.

Having concluded that abiotic terrestrial mechanisms would have been ineffectual for the origin of terrestrial homochirality, we have proposed an alternative extraterrestrial scenario involving stereoselective ultraviolet photolysis of the racemic constituents of interstellar grain mantles by circularly polarized synchrotron radiation from neutron stars, followed by terrestrial accretion of the resulting chiral molecules via cometary impact. Recently L. Keszthelyi (1995) has reviewed a number of our arguments and advanced several erroneous calculations and conclusions purporting to negate them. We offer here points of rebuttal to Keszthelyi's criticisms, and support our inferences with recent data regarding indigenous enantiomeric excesses of L-amino acids in the Murchison meteorite.

Tracking the organic refractory component from interstellar dust to comets.

The abundance and composition of complex organic (carbonaceous) material in the interstellar dust is followed as the dust evolves in its cyclic evolution between diffuse and dense clouds. Interstellar extinction, laboratory and space analog experiments, dust infrared absorption spectra, the cosmic abundance of the condensible atoms, and space and ground-based observations of comet dust are used to impose constraints on the organic dust component as mantles on silicate cores.

Alveolar capillary dysplasia with misalignment of the pulmonary veins: a rare but fatal cause of neonatal respiratory failure.

Respiratory failure in the neonate that is refractory to maximal medical management is a frequent indication for extracorporeal life support (ECLS). Alveolar capillary dysplasia with misalignment of the pulmonary veins is an irreversible cause of respiratory failure that cannot be diagnosed on clinical grounds alone and would not be expected to respond to ECLS therapy. A recent experience with a patient prompted us to review the literature regarding this condition for the purpose of identifying factors suggestive of this diagnosis. This condition should be considered in neonates with presumed pulmonary hypertension who cannot be weaned from ECLS. If the diagnosis is made by antemortem open-lung biopsy, a costly, protracted, and unnecessary continued course of ECLS may be avoided.

Evolution of interstellar dust and its relevance to life's origin: laboratory and space experiments.

A scheme is presented for an analog investigation of long term irradiation of ices and organics following the cyclic evolution of interstellar dust. The irradiation is proposed to be performed at cryogenic temperatures on a space platform, and with an enhancement of the solar ultraviolet flux using a concave mirror, grating combination which eliminates the visual and infrared from the sample surface.

Comets as porous aggregates of interstellar dust.

A comet model is derived based on the interstellar dust chemical composition in dense molecular and diffuse clouds resulting from their subsequent chemical interactions and UV photoprocessing. The collapsing presolar nebula leads to a porous aggregate model for comet nuclei, from which is derived certain physical properties that include thermal conductivity and tensile strength. The porous morphological structure is also shown to imply anomalous (expansion rather than contraction) behavior when subjected to strong shock waves, which is supported by recent shock experiments on (porous) carbonaceous chondrite material.

From the interstellar clouds, through the inner to the outer solar system: a universally distributed complex organic chemistry. Preface.

High molecular weight organic compounds are involved in the chemistry and physics of many astrophysical and planetary objects. They are or should be present in interstellar dust, in comets and meteorites, in the Giant planets and Titan, in asteroids Triton and icy satellites. They represent a class of very complex organic material, part of which may have played a role in the origin of life on Earth. Thus they directly concern prebiotic chemistry and exobiology.

Silicate core-organic refractory mantle particles as interstellar dust and as aggregated in comets and stellar disks.

The principal observational properties of silicate core-organic refractory mantle interstellar dust grains in the infrared at 3.4 microns and at 10 microns and 20 microns are discussed in terms of the cyclic evolution of particles forming in stellar atmospheres and undergoing subsequent accretion, photoprocessing and destruction (erosion). Laboratory plus space emulation of the photoprocessing of laboratory analog ices and refractories are discussed. The aggregated interstellar dust model of comets is summarized. The same properties required to explain the temperature and infrared properties of comet coma dust are shown to be needed to account for the infrared silicate and continuum emission of the beta Pictoris disk as produced by a cloud of comets orbiting the star.