Associations between ethnicity and admission to intensive care among women giving birth: a cohort study.

OBJECTIVE: To determine the association between ethnic group and likelihood of admission to intensive care in pregnancy and the postnatal period. DESIGN: Cohort study. SETTING: Maternity and intensive care units in England and Wales. POPULATION OR SAMPLE: A total of 631 851 women who had a record of a registerable birth between 1 April 2015 and 31 March 2016 in a database used for national audit. METHODS: Logistic regression analyses of linked maternity and intensive care records, with multiple imputation to account for missing data. MAIN OUTCOME MEASURES: Admission to intensive care in pregnancy or postnatal period to 6 weeks after birth. RESULTS: In all, 2.24 per 1000 maternities were associated with intensive care admission. Black women were more than twice as likely as women from other ethnic groups to be admitted (odds ratio [OR] 2.21, 95% CI 1.82-2.68). This association was only partially explained by demographic, lifestyle, pregnancy and birth factors (adjusted OR 1.69, 95% CI 1.37-2.09). A higher proportion of intensive care admissions in Black women were for obstetric haemorrhage than in women from other ethnic groups. CONCLUSIONS: Black women have an increased risk of intensive care admission that cannot be explained by demographic, health, lifestyle, pregnancy and birth factors. Clinical and policy intervention should focus on the early identification and management of severe illness, particularly obstetric haemorrhage, in Black women, in order to reduce inequalities in intensive care admission. TWEETABLE ABSTRACT: Black women are almost twice as likely as White women to be admitted to intensive care during pregnancy and the postpartum period; this risk remains after accounting for demographic, health, lifestyle, pregnancy and birth factors.

Waterbirth: a national retrospective cohort study of factors associated with its use among women in England.

BACKGROUND: Waterbirth is widely available in English maternity settings for women who are not at increased risk of complications during labour. Immersion in water during labour is associated with a number of maternal benefits. However for birth in water the situation is less clear, with conclusive evidence on safety lacking and little known about the characteristics of women who give birth in water. This retrospective cohort study uses electronic data routinely collected in the course of maternity care in England in 2015-16 to describe the proportion of births recorded as having occurred in water, the characteristics of women who experienced waterbirth and the odds of key maternal and neonatal complications associated with giving birth in water. METHODS: Data were obtained from three population level electronic datasets linked together for the purposes of a national audit of maternity care. The study cohort included women who had no risk factors requiring them to give birth in an obstetric unit according to national guidelines. Multivariate logistic regression models were used to examine maternal (postpartum haemorrhage of 1500mls or more, obstetric anal sphincter injury (OASI)) and neonatal (Apgar score less than 7, neonatal unit admission) outcomes associated with waterbirth. RESULTS: 46,088 low and intermediate risk singleton term spontaneous vaginal births in 35 NHS Trusts in England were included in the analysis cohort. Of these 6264 (13.6%) were recorded as having occurred in water. Waterbirth was more likely in older women up to the age of 40 (adjusted odds ratio (adjOR) for age group 35-39 1.27, 95% confidence interval (1.15,1.41)) and less common in women under 25 (adjOR 18-24 0.76 (0.70, 0.82)), those of higher parity (parity ≥3 adjOR 0.56 (0.47,0.66)) or who were obese (BMI 30-34.9 adjOR 0.77 (0.70,0.85)). Waterbirth was also less likely in black (adjOR 0.42 (0.36, 0.51)) and Asian (adjOR 0.26 (0.23,0.30)) women and in those from areas of increased socioeconomic deprivation (most affluent versus least affluent areas adjOR 0.47 (0.43, 0.52)). There was no association between delivery in water and low Apgar score (adjOR 0.95 (0.66,1.36)) or incidence of OASI (adjOR 1.00 (0.86,1.16)). There was an association between waterbirth and reduced incidence of postpartum haemorrhage (adjOR 0.68 (0.51,0.90)) and neonatal unit admission (adjOR 0.65 (0.53,0.78)). CONCLUSIONS: In this large observational cohort study, there was no association between waterbirth and specific adverse outcomes for either the mother or the baby. There was evidence that white women from higher socioeconomic backgrounds were more likely to be recorded as giving birth in water. Maternity services should focus on ensuring equitable access to waterbirth.

Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study.

BACKGROUND: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. METHODS: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. RESULTS: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. CONCLUSION: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

Hookworm: developmental biology of the infectious process.

Hookworms cause severe anemia and malnutrition in developing countries of the tropics, with an estimated one billion people infected worldwide. An in vitro system that models the early events of infection has provided new information about the linkage between the infectious process and the parasite's developmental biology. The cloning and expression of Ancylostoma secreted protein, ASP 1 - a secreted molecule associated with these developmental processes - is an example of how this system allows us to dissect the infectious process at the molecular level.

Quantitative ultrasound (QUS): a useful tool for monitoring bone health in preterm infants?

UNLABELLED: Preterm infants are at risk of osteopenia and metabolic bone disease (MBD) of prematurity. There is a need for simple, reliable methods to detect and monitor this condition. AIMS: The aims were first to describe longitudinal changes in speed of sound (SOS) measured using quantitative ultrasound (QUS; Sunlight Omnisense, Israel) in preterm neonates: and second to determine whether SOS predicts the development of MBD. METHODS: SOS was measured in the tibia in 99 preterm infants (mean (SD)) gestation 29.7 (3.6) weeks; birthweight 1340 (550) g, with longitudinal measurements in 75. SOS z-scores were generated for gestation and sex. Clinical data were recorded. RESULTS: Baseline SOS (but not SOS z-score) was positively associated with gestational age. SOS and SOS z-score fell with age. In multivariate models, peak ALP, minimum phosphate concentrations and markers of illness severity were not predictors of the fall in SOS z-score, and baseline SOS measurements did not predict the development of high peak ALP or low phosphate. INTERPRETATION: Speed of sound measurements fell with age in all infants, but we found no evidence that this measurement could predict biochemical indicators of MBD. We cannot exclude the possibility that this technique could be useful in monitoring the response to interventions designed to improve bone health in this population.

Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants.

BACKGROUND: Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. AIM: To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. METHODS: A randomised, double blind trial of oxytocin nasal spray (100 microl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. MAIN OUTCOME: Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). SECONDARY OUTCOMES: Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 ("physiological study"); mother's opinion of expressing and spray assessed by questionnaire. RESULTS: Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p = 0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers' opinions of milk expression and treatment. CONCLUSIONS: Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding support available during the study.

Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans.

Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. Mutant homozygotes have normal growth rates and no obvious morphological or developmental abnormalities. The mutant gene (cad-1) has been mapped to the right extremity of linkage group II. Heterozygous animals (cad-1/+) show intermediate enzyme levels and animals heterozygous for chromosomal deficiencies of the right extremity of linkage group II have 50% of wild-type activity. Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. These data suggest that cad-1 is a structural gene for cathepsin D.

Decline in protease activities with age in the nematode Caenorhabditis elegans.

The activities of 3 lysosomal proteases in the nematode Caenorhabditis elegans are markedly lower in older animals. The aspartyl protease cathepsin D declines about 10-fold from day 3 (early adulthood) to day 11 (near the mean lifespan); this reflects a net decline in the amount of cathepsin D antigen. The specific activity of the thiol protease cathepsin Ce1 declines about 2.5-fold over the same period, and the specific activity of the thiol protease cathepsin Ce2 declines about 8-fold. The activity of a new non-lysosomal protease, designated cathepsin CeX, is invariant with age. The data are consistent with the hypothesis that reduced protease activity in older animals may cause a decline in the rate of protein turnover with age, but do not prove this hypothesis.

Ancylostoma secreted protein 2: cloning and characterization of a second member of a family of nematode secreted proteins from Ancylostoma caninum.

Invading infective third-stage larvae (L3) of parasitic nematodes execute a series of programmed developmental events in response to a host-specific signal encountered during infection. One of these early events is the release of excretory/secretory products. Using an in vitro feeding assay that mimics these early events of infection, a protein released by in vitro activated larvae of the hookworm Ancylostoma caninum was identified. This protein, Ac-ASP-2, was partially sequenced, and the cDNA encoding it isolated by PCR and screening of an A. caninum L3 cDNA library. The Ac-asp-2 cDNA encodes a protein of 219 amino acids that is related to a previously identified protein, Ac-ASP-1, from hookworms. Both molecules are members of an evolutionarily diverse family of molecules that include the venom allergens of the Hymenoptera, and the testes specific proteins/sperm-coating glycoproteins of mammals. Homologues are present in nearly all nematodes tested, as demonstrated by PCR-hybridization and database searching. The Ac-asp-2 mRNA is synthesized in all life history stages, but the gene product is released only by L3 activated to feed in vitro. The wide distribution of the Ac-asp-2 in nematodes and its release in response to host specific signals suggests that Ac-ASP-2 serves an important function in nematode physiology and development, and possibly in the infective process of parasitic species.

Ancylostoma caninum anticoagulant peptide: cloning by PCR and expression of soluble, active protein in E. coli.

Ancylostoma caninum Anticoagulant Peptide (AcAP) is the major anticoagulant activity present in extracts of adult Ancylostoma caninum hookworms. This 8.7 kDa protein is a potent and specific inhibitor of human coagulation factor Xa. Using PCR, we have isolated a cDNA encoding for AcAP from an adult A. caninum cDNA library. The 5' end of the AcAP cDNA was identified by reverse transcription PCR (RT-PCR) using A. caninum cDNA and a 5' primer corresponding to a nematode spliced leader sequence. The AcAP cDNA was expressed in E. coli using a prokaryotic expression vector, and the recombinant fusion protein (rAcAP) was purified to homogeneity using nickel resin affinity chromatography and reverse phase HPLC. Purified rAcAP is comparable to the native protein in inhibitor activity, with an apparent equilibrium inhibitory dissociation constant (Ki*) for the inhibition of factor Xa of 265 +/- 71 pM. The purified protein also prolongs the prothrombin and partial thromboplastic times of human plasma in a dose dependent manner.

Epidemiology of human hookworm infections among adult villagers in Hejiang and Santai Counties, Sichuan Province, China.

Hookworm infection as well as other intestinal nematodiases are endemic to Sichuan Province in China. In order to research the prevalence and intensity of these infections we visited two villages in Hejiang County (southern Sichuan Province) and Santai County (northwestern Sichuan Province) between July and October of 1997. Fecal examinations were performed on adult villagers over the age of 15 years (currently children under this age are dewormed annually with anthelmintic drugs). Among 310 residents of Lugao Village (Hejiang County), 87, 63 and 60% were infected with hookworm, Ascaris or Trichuris, respectively. The prevalence of hookworm determined to rise linearly with age (r = 0.97). High intensity infections with hookworm still occur in this region as 22% of the residents have over 3000 eggs per gram (PEG) of feces as determined by quantitative egg counts. The majority of these individuals harbored mixed infection with Necator americanus and Ancylostoma duodenale, although the former predominated when adult hookworms were collected from 30 village residents treated with pyrantel pamoate. In contrast, among the 334 Xinjian villagers examined (Santai County) the majority harbored predominantly light hookworm infections--66.1% of the residents has less than 400 EPG by quantitative fecal examination and only 3.7% exhibited greater than 3000 EPG. Again, N. americanus was the predominant hookworm seen after worm expulsion. We have round that despite economic development which is occurring in some parts of China, significant hookworm infections and clinical hookworm anemia still exist in areas of Sichuan Province. In Hejiang County we found that the intensity of hookworm infection has actually risen within the last 10 years. Hookworm is a medical problem among the elderly in Sichuan.

Use of specific immunoradiometric assay to determine preterm neonatal insulin-glucose relations.

Highly specific immunoradiometric assays were used to measure plasma concentrations of insulin, proinsulin, and 32-33 split proinsulin in neonates (n = 16). Neonatal plasma insulin concentrations were high relative to blood glucose concentrations and compared with adult insulin-glucose relations. Concentrations of proinsulin and 32-33 split proinsulin together accounted for 34-70% of the total concentration of insulin and pro-peptides. This study confirms the need to use a specific assay and neonatal reference data in the diagnosis of neonatal hyperinsulinism, and shows that neonatal pancreatic beta cell function may differ from that of older subjects.

Efficacy of an ivermectin/pyrantel pamoate chewable formulation against the canine hookworms, Uncinaria stenocephala and Ancylostoma caninum.

The effectiveness of the combination of pyrantel pamoate (5 mg kg-1) and ivermectin (6 micrograms kg-1) against the canine hookworms Uncinaria stenocephala and Ancylostoma caninum was determined. This combination is intended for monthly use as a heartworm preventative and for treatment and control of canine hookworms. The formulation was found to be effective (99.6% reduction in worm burdens) against both species of hookworms in experimentally infected dogs. No adverse effects due to the drug combination were observed in any dog during the course of this study.

Differentiation between the human hookworms Ancylostoma duodenale and Necator americanus using PCR-RFLP.

There are 2 major species of hookworms that infect humans. Ancylostoma duodenale and Necator americanus. Although traditionally considered to be identical for treatment purposes, there are significant life history differences between the species that must be considered for the rational design of chemotherapeutic and immunoprophylactic control strategies. However, identification of the species infecting a particular population has been problematic, as the eggs of the 2 species cannot be reliably differentiated by classical parasitological methods. A PCR-based technique for the differentiation of hookworm species that infect humans is reported. A fragment of the 3' untranslated region of the cAMP-dependent protein kinase catalytic subunit gene was amplified from A. duodenale and N. americanus genomic DNA using primers derived from the corresponding A. caninum cDNA. Digestion of the amplified DNA with the restriction enzymes HpaII, MboI, TaqI, and ThaI generated specific restriction fragment patterns unique to each species. The technique can distinguish between pure and mixtures of hookworm DNA and can amplify DNA from a single egg. The primers also amplify the fragment from the DNA of several other species of hookworms that infect humans and other animals. The technique is fast, simple, and hookworm specific and represents a considerable savings in time over current methods used for distinguishing between human hookworm infections.

Albumin and a dialyzable serum factor stimulate feeding in vitro by third-stage larvae of the canine hookworm Ancylostoma caninum.

Previous studies demonstrated that third-stage, developmentally arrested larvae of the canine hookworm Ancylostoma caninum resume feeding in vitro in response to canine serum and hostlike temperature. Experiments to determine the identity of the serum stimulus are described. Serum from several nonhost species stimulated feeding, but to levels lower than canine serum. Heating the serum to 57 C had no effect on its stimulatory ability. Dialysis reduced serum stimulatory activity by 50%, and ultrafiltration through 10- and 30-kDa molecular weight cut-off membranes decreased activity in both the filtrates and retentates similarly. Recombination of the filtrates and retentates restored activity to whole serum control levels. Commercial canine and bovine albumin stimulated feeding to serum control levels at 10 and 50 mg/ml, respectively. These results suggest that albumin and an unidentified low molecular weight compound(s) are capable of inducing in vitro feeding by A. caninum L3.

Serum-stimulated feeding in vitro by third-stage infective larvae of the canine hookworm Ancylostoma caninum.

Developmentally arrested nonfeeding infective larvae of hookworms resume development after entry into the host, presumably in response to a signal encountered during invasion. Logically, an initial step in the resumption of development might be the resumption of feeding. An in vitro assay for feeding is described for the third-stage larvae of the canine hookworm Ancylostoma caninum. Populations of larvae incubated under hostlike conditions in the presence of 10% canine serum resume feeding within 6 hr, as evidenced by the uptake of fluorescein-labeled bovine serum albumin. Feeding is dependent on the presence of canine serum, and peaks by 24 hr incubation. Maximal feeding levels occur at temperatures above 34 C with a gas phase of 5% CO2/95% air, whereas culture medium and pH are unimportant for feeding. Serum concentrations between 0.1% and 1.0% (v/v) initiate feeding, and the response peaks at approximately 8.0% serum. Serum triggers feeding within 6 hr and is not required for feeding to continue once initiated. The saturation effect and the trigger phenomenon suggest that the initiation of feeding is a receptor-mediated response.

Species-specific identification of human hookworms by PCR of the mitochondrial cytochrome oxidase I gene.

Significant differences in the life histories of the human hookworms Ancylostoma duodenale and Necator americanus necessitate their differentiation for epidemiological studies and the design of control programs. Current methods of identification require time-consuming, labor-intensive techniques. A polymerase chain reaction (PCR)-based method that enables rapid species identification is described. The mitochondrial cytochrome oxidase I genes of both species were sequenced, and species-specific primer sets were designed. The primers were used in PCR to amplify 585-bp fragments of the cytochrome oxidase gene from individual hookworm eggs, larvae, and adults. The technique was also able to identify mixed infections containing equal amounts of eggs from each species. The technique is rapid, technically simple, and sensitive and will permit the accurate identification of human hookworms in epidemiological field studies.

Resumption of feeding in vitro by hookworm third-stage larvae: a comparative study.

Third-stage infective larvae of the canine hookworm Ancylostoma caninum resume feeding in vitro in response to several stimuli. Experiments were conducted to characterize the in vitro feeding behavior of several hookworm species. Reduced glutathione and, to a lesser extent, canine and human serum stimulated third-stage larvae of Ancylostoma duodenale to resume feeding. Glutathione-induced feeding reached a maximum by 16 hr and was concentration-dependent between 0- and 15-mM glutathione. Oxidized glutathione and the reducing agents dithiothreitol and L-cysteine failed to induce feeding, suggesting that reducing conditions alone were not stimulatory. Serum incubated with glutathione was the most efficient stimulus for Ancylostoma ceylanicum, Ancylostoma braziliense, and Ancylostoma tubaeforme larvae, whereas Uncinaria stenocephala larvae responded best to canine serum alone. Necator americanus larvae did not resume feeding in response to glutathione, serum, glutathione plus serum, or linoleic acid (0.1-10 mM). These differences in feeding behavior suggest that generalizations concerning hookworm biology must be interpreted cautiously.