Maternal health, pregnancy and birth outcomes for women involved in care proceedings in Wales: a linked data study.

BACKGROUND: Under the Children Act 1989, local authorities in Wales, UK, can issue care proceedings if they are concerned about the welfare of a child, which can lead to removal of a child from parents. For mothers at risk of child removal, timely intervention during pregnancy may avert the need for this and improve maternal/fetal health; however, little is known about this specific population during the antenatal period. The study examined maternity characteristics of mothers whose infants were subject to care proceedings, with the aim of informing preventative interventions targeted at high risk mothers. METHODS: Anonymised administrative data from Cafcass Cymru, who provide child-focused advice and support for family court proceedings in Wales, were linked to population-based maternity and health records held within the Secure Anonymised Information Linkage Databank. Linked data were available for 1111 birth mothers of infants involved in care proceedings between 2015 and 2018. Findings were benchmarked with reference to an age-deprivation-matched comparison group (n = 23,414), not subject to care proceedings but accessing maternity services during this period. Demographic characteristics, maternal health, reproductive history, interaction with midwifery services, and pregnancy and birth outcomes were examined. Descriptive and statistical tests of independence were used. RESULTS: Half of the women in the cohort (49.4%) resided in the most deprived areas. They were more likely to be younger at entry to motherhood (63.5% < 21 years-of-age compared to 42.7% in the comparison group), to have mental health (28.6% compared to 8.2%) and substance use issues (10.4% compared to 0.6%) and to smoke (62.7% compared to 24.8%) during pregnancy. The majority first engaged with maternity services within their first trimester of pregnancy (63.5% compared to 84.4%). Babies were more likely to be born preterm (14.2% compared to 6.7%) and, for full-term babies, to have low birthweights (8.0% compared to 2.8%). CONCLUSION: This novel linkage study highlights multiple vulnerabilities experienced by pregnant mothers who have experienced care proceedings concerning an infant. Policy and practice colleagues require a clearer picture of women's needs if child protection and health services are to offer effective services which prevent the need for family court proceedings and infant removal.

Linking data on women in public family law court proceedings concerning their children to mental health service records in South London.

INTRODUCTION: Maternal mental health problems and substance misuse are key risk factors for child neglect or abuse and court-mandated placement into care. Linkage between mental health records and family court data could raise awareness about parent mental health needs and inform approaches to address them. OBJECTIVES: To evaluate data linkage between administrative family court data and electronic mental health records for a population-based mental health service for 1.3 million people in South London. METHODS: We deterministically linked administrative family court data for women (n=5463) involved in care proceedings in South London with service user records from the South London and Maudsley NHS Mental Health Trust (SLaM). We restricted the cohort to women involved in proceedings between 2007 and 2019, in local authorities where SLaM solely provides secondary/tertiary mental health services and the Improving Access to Psychological Therapies (IAPT) (n=3226). We analysed the associations between match status and sociodemographic/case characteristics using multivariable logistic regression. RESULTS: Two-thirds (2317/3226; 66%) of women linked to a SLaM service user record at some point; most (91%) who linked accessed secondary/tertiary mental health services, indicating serious mental illness. Accounting for possible missed matches, we estimated that 70-83% of women accessed SLaM services at some point. Older women at index proceedings (>35yrs OR: 0.69, 95%CI: 0.54-0.88vs <25yrs) and Black women or women from other ethnic groups (Black ethnic groups 0.65, 0.50-0.83; other ethnicity 0.59, 0.43-0.81 vs White ethnic groups) had lower odds of linking. Odds of linking were higher for women with an infant in proceedings (1.42, 1.18-1.71), or with curtailed/terminated parental responsibility (1.44, 1.20-1.73). CONCLUSION: Our linkage supports growing evidence of a high burden of mental health problems and substance misuse among women whose children enter care in England, compared to the general population. Research using this linkage should inform strategies to address the considerable mental health needs of vulnerable women and their children.

Data Resource: Children and Family Court Advisory and Support Service (Cafcass) public family law administrative records in England.

INTRODUCTION: In England, in cases of child maltreatment or neglect, the state can intervene through the family court to remove children from their family home and place them in out-of-home care. The Children and Family Court Advisory and Support Service (Cafcass) collects and maintains administrative records of all public family law cases in England. While these national records are primarily used to monitor and manage the workflow of Cafcass teams across England, researchers have re-purposed this data for analysis to understand the drivers and outcomes of public family law intervention. DATA CONTENTS: The administrative dataset is a reflection of the cases Cafcass is involved with and the extent of that involvement. The dataset contains information about the local authority that makes an application to initiate public family law proceedings, the children and families involved, and the duration and details of the case. Between 1 April 2007 and 31 March 2019, Cafcass captured information on approximately 172,100 public family law cases, involving 282,300 children, and 349,600 adults (of which 289,300 are recorded as biological parents). Amongst the information recorded are the relations between adults and children, making it possible for researchers to identify family groups. Additionally, recording practices at Cafcass have improved over time, this has increased the availability of demographic information of all those involved, as well as child's final legal outcome. DATA ACCESS: Researchers can apply to the Secure Anonymised Information Linkage databank (SAIL) for access to the Cafcass pseudonymised administrative data extract, where it is refreshed bi-annually. KEYWORDS: children, out of home care, family relations, family law.

Data Resource: population level family justice administrative data with opportunities for data linkage.

INTRODUCTION: Although there has been considerable progress in the use of administrative data for applied health research, the family justice field lags behind. Better use of administrative data are essential to enhance understanding of how the family justice system is working, as well as the characteristics of, and outcomes for, children and families. The Family Justice Data Partnership (FJDP) supports this aim through analyses of core family justice and linked datasets in the SAIL Databank (Secure Anonymised Information Linkage). Cafcass Cymru provide expert advice for children involved in family court proceedings in Wales, ensuring decisions are made in the best interests of the child. We provide an overview of Cafcass Cymru data. We also describe and illustrate linkage to administrative datasets within SAIL. METHODS: Cafcass Cymru data was transferred to SAIL using a standardised approach to provide de-identified data with Anonymised Linking Fields (ALF) for successfully matched records. Three cohorts were created: all individuals involved in family court applications; all individuals with an ALF allowing subsequent health data linkage; and all individuals with a Residential Anonymised Linking Field (RALF) enabling area-level deprivation analysis. RESULTS: Cafcass Cymru application data are available for child protection matters (public law, range 2011-2019, n=12,745), and child arrangement disputes (private law, range 2005-2019, n=52,023). An 80% data linkage match rate was achieved. 40% had hospital admissions within two years pre or post application; 54% had emergency department attendances and 61% had outpatient appointments. Individuals were more likely to reside in deprived areas regardless of law type. CONCLUSION: Cafcass Cymru data can be accessed through the SAIL Databank. The FJDP will continue to enhance research opportunities for all to better understand the family justice system, and outcomes for those involved, such as health and wellbeing for children and family members.

Immunodetection of aldose reductase in normal and diseased human liver.

Aldose reductase is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway that is implicated in the complications of diabetes. Aldose reductase appears to be involved in a variety of disease states other than diabetes, presumably due to its ability to catalyze the reduction of a broad spectrum of aldehydes, including some cytotoxic products of lipid peroxidation. Although the data regarding expression of aldose reductase in normal liver are conflicting, prior studies have suggested that the enzyme may be induced in diseased liver. The goal of these studies was to characterize expression of aldose reductase in normal and diseased human liver, using RT-PCR, Western analysis and immunohistochemistry. Aldose reductase transcripts and protein were detected at low levels in control human livers. In contrast, levels of aldose reductase mRNA and protein were increased in chronically diseased human livers. Immunohistochemistry demonstrated localization of aldose reductase in sinusoidal lining cells; dual immunofluorescence confocal microscopy with the macrophage marker, CD68, confirmed that the aldose reductase-positive sinusoidal lining cells were Kupffer cells. Abundant aldose reductase-positive, CD68-positive cells were present in the fibrous septa of cirrhotic livers, accounting for the increase in immunoreactive aldose reductase in diseased livers. Immunostaining of human lung, spleen and lymph node revealed that macrophages in those tissues also express aldose reductase. These data are the first to demonstrate that aldose reductase is expressed by human macrophages in various tissues and suggest that this enzyme may play a role in immune or inflammatory processes.

Gastric contractions, secretions and injury in cold restraint.

The clinical syndrome of stress ulceration has been studied for years using rodent cold restraint stress models, although the pathogenesis of the characteristic focal gastric mucosal lesions produced in these models has been controversial. We used gastric strain gauges to characterize fully the gastric motility effects of a 4-h cold restraint protocol, and we determined the relationship of variations in gastric contents and in gastric contractions to the amount of gastric mucosal injury. Additionally, we examined rat stomachs histologically, and determined the location of focal haemorrhagic mucosal lesions on the mucosal rugae. We found a consistent relationship between force of gastric contractions and gastric mucosal injury, and also a relationship between the initial duration of contractions during restraint and ultimate mucosal injury. Volume, acidity and mucus in the gastric contents were unrelated to mucosal injury. The majority (91%) of the mucosal lesions had some relationship to a rugal fold, with 59% of all lesions at the base of a rugal fold. Thus, the mechanical forces of gastric hypercontractility may contribute to the gastric mucosal injury of rodent cold restraint models.

Gastric mucosal protection from enteral nutrients: role of motility.

BACKGROUND: Cold restraint stress increases the force of gastric contractions and produces gastric mucosal injury in rats. The aim of our study was to determine whether enteral glucose or hyperglycemia alone would alter the stress-induced gastric motility pattern and ameliorate the associated gastric mucosal injury. METHODS: Adult male rats underwent surgical placement of gastric catheters, jugular venous catheters, and gastric strain gauge transducers 5 days before cold restraint. Three groups of rats received different substances during the same cold restraint stress protocol. Group 1 received 0.9% NaCl, 2 mL/h infused both intravenously (i.v.) and intragastrically (i.g.); group 2 received 0.9% NaCl, 2 mL/h i.g. plus 25% glucose, 2 mL/h i.v.; and group 3 received 0.9% NaCl, 2 mL/h i.v. plus 25% glucose i.g. Following baseline gastric motility measurements, all rats were restrained for 2 hours at 20 degrees C followed by 2 hours at 4 degrees C. RESULTS: Restraint even at room temperature increased the force of gastric contractions; the cold environment gradually prolonged gastric contractions. Enteral glucose blunted the effects of stress on gastric motility, increased gastric residual volume, decreased gastric acidity, and prevented gastric mucosal injury. Parenteral glucose had little effect on any gastric parameters. CONCLUSIONS: Enteral glucose prevents the abnormal gastric motility pattern that is necessary to produce the gastric mucosal injury associated with cold restraint stress, but hyperglycemia alone has little effect on the pathophysiology of cold restraint.

Replantation of the upper extremity in children.

Since Malt and McKhann performed the first successful replantation of a traumatically amputated extremity in 1962, there has been a flurry of case reports and articles debating the pros and cons of the various technical aspects of replantation. There have been three case reports of children, under the age of 15, who have successfully undergone replantation of the upper extremity transected throught the humerus. The first case report in this article is the fourth. The factors involved in selecting replantation or amputation, and the technical aspects of the operation which are felt to be important, are briefly reviewed. Because the mechanics of limb replantation are rather straightforward, we feel that the pediatric surgeon should be familar with the preoperative and intraoperative factors to be weight, and that this alternative to stump closure be carefully considered when one is presented with an upper extremity transection.

The role of platelet-activating factor in conscious, normotensive endotoxemia.

The effects of endotoxin have been postulated to be mediated in large part by release of endogenous platelet-activating factor (PAF) due to the similarity of their hemodynamic and gastric effects in anesthetized animals, and to the ability of PAF inhibitors to ameliorate endotoxin's effects. We chose to examine the relationship with doses that would not produce circulatory shock, in unrestrained conscious animals, in order to mimic clinical situations. Adult male rats were prepared with vascular access, hemodynamic and temperature monitors, and gastric strain gauge transducers. After an overnight fast, rats received a 4-hr infusion of saline (0.5 ml/hr), endotoxin (12.5 mg/kg/hr), PAF (36 micrograms/kg/hr, or 600 ng/kg/min), or endotoxin plus the PAF inhibitor CV 3988 (1 mg/kg/hr, after an initial pretreatment of 1 mg/kg). Rats were killed, stomachs were harvested, and contents were analyzed at the end of the infusions. Blood pressure was not affected by any treatment, but all treated groups developed diarrhea and vasodilatation. Endotoxin and PAF infusions decreased heart rate and body temperature to a similar extent, although the PAF effect on temperature was delayed. The PAF inhibitor did not prevent the body temperature effect, but did reverse it. Gastric secretions were affected by PAF to a lesser extent than by endotoxin, and the PAF inhibitor did not decrease endotoxin's gastric secretory effects. PAF has similar systemic and gastric effects to endotoxin in conscious, unrestrained, normotensive animals. The systemic effects of endotoxin at 12.5 mg/kg/hr were prevented or reversed by the PAF inhibitor CV-3988 at 1 mg/kg/hr, but not the gastric secretory effects.

Captopril decreases stress ulceration without affecting gastric perfusion during canine hemorrhagic shock.

The renin-angiotensin axis has recently been called the source of disproportionate splanchnic vasoconstriction during shock, and blocking this axis decreased gastric stress ulceration during swine cardiogenic shock. The present study tested whether the angiotensin converting enzyme inhibitor captopril would prevent stress ulceration when given after the onset of canine hemorrhagic shock, and whether any detrimental effects would result from enhancing splanchnic perfusion with captopril during hemorrhagic shock. We found that captopril treatment was associated with a decrease in gastric mucosal injury and with a marked decrease in systemic acidosis. Captopril enhanced blood flow to the small intestine, pancreas, liver, and spleen, but not flow to the stomach, during shock. Following the reinfusion of shed blood, the captopril-treated animals had decreased mean blood pressures and increased heart rates compared with untreated animals. We found captopril alleviated the stress ulceration produced by canine hemorrhagic shock, but concluded that the likely mechanism was alleviating systemic acidosis through enhanced perfusion of other viscera rather than a specific enhancement of gastric perfusion.

Effects of intragastric and intravenous glucose on restraint model of stress ulceration.

Intragastric glucose prevents acute stress-induced gastric mucosal injury in the restrained rat. Because increased gastric contractions contribute to mucosal injury in this model and because parenteral glucose infusions have been shown to suppress gastric contractility, we hypothesized that centrally mediated responses to hyperglycemia might contribute to the cytoprotective effect of intragastric glucose. We compared intragastric and intravenous 25% glucose with saline infusions during cold restraint and measured their impact on gastric lesions, serum glucose levels, gastric residual volume (an indirect indicator of net gastric contractility), acidity, and mucin concentration. We found that both intravenous and intragastric glucose infusions increased serum glucose to over 500 mg/dl after 4 hr of stress. Intragastric glucose increased residual volume and gastric pH, as well as decreased gastric mucosal injury, but intravenous glucose had no effects on gastric function. We found that none of the potentially protective effects of intragastric glucose are mediated by central responses to hyperglycemia, and likewise that intravenous glucose has no effect on gastric mucosal injury.

Are gastric, jejunal, or both forms of enteral feeding gastroprotective during stress?

BACKGROUND: Clinical data suggest enteral nutrition prevents stress ulceration and intragastric nutrients prevent restraint-induced gastric injury. The purpose of these studies was to determine if jejunal nutrients can protect without gastric contact and to determine if gastric pH, motility, or mucosal perfusion is affected. METHODS: In Experiment 1, 27 rats were restrained for 2 h at room temperature followed by 2 h in cold (4 degrees C), with intragastric (IG) or intrajejunal (IJ) 2 ml/h infusions of saline or 25% glucose. Gastric lesions, pH, volumes, and glucose concentrations were measured postmortem. In Experiment 2, 23 rats had gastric strain gauges implanted >5 days prior to a 0.5 ml/h IG or IJ infusion during stress. In Experiment 3, 40 rats were anesthetized for laser Doppler measurements of gastric mucosal perfusion and arterial catheter monitoring of systemic hemodynamics. Rats received 0.5-ml boluses of concentrated glucose or saline IG or IJ, and were monitored for 60 min. RESULTS: (1) The 2 ml/h IJ and IG glucose infusions prevented gastric injury, but the elevated gastric glucose concentrations suggested equal gastric contact. (2) The 0.5 ml/h glucose IG and IJ infusions decreased gastric injury without reflux of the IJ glucose into the stomach and suppressed stress-induced hypercontractility, but not acidity. (3) Systemic perfusion pressures were unaffected by enteral glucose. IG glucose had little effect on gastric mucosal perfusion, while IJ glucose decreased gastric perfusion within 5 min. CONCLUSIONS: These studies show that large volumes of enteral glucose prevent restraint injury but IJ glucose refluxes into the stomach. The gastroprotective effects of small, nonrefluxing volumes of IJ glucose are associated with suppression of stress-induced gastric hypercontractility, but not with suppressed acidity or enhanced perfusion.

Changes in intestinal transit and absorption during endotoxemia are dose dependent.

BACKGROUND: Septic patients are often intolerant of enteral feedings due to a combination of motility disturbances and impaired absorptive function. Our laboratory has previously demonstrated that endotoxemia results in rapid intestinal transit and decreased jejunal absorption of water, electrolytes, and glucose. We hypothesized that the changes in jejunal transit and absorption during endotoxemia may be dependent on the dose of endotoxin. MATERIALS AND METHODS: Under general anesthesia, rats underwent placement of an internal jugular line, a femoral arterial line, and a 20-cm jejunal Thiry-Vella loop. The jejunal segment was perfused with an isotonic solution containing polyethylene glycol. For 90 min, baseline measurements of blood pressure, heart rate, jejunal absorption of water, electrolytes, and glucose, and jejunal transit were made. Following this baseline period I, rats were given 0.9% NaCl (1 ml/kg) or one of three doses of Escherichia coli lipopolysaccharide (0.5, 1.0, or 5.0 mg/kg). Studies were then repeated for an additional 90 min. RESULTS: Changes in blood pressure and heart rate were similar among the four groups of animals. Endotoxin decreased water and glucose flux, increased potassium flux, and quickened intestinal transit in a dose-dependent fashion. CONCLUSIONS: We conclude that endotoxemia causes dose-dependent changes in jejunal transit and absorption. The effects of increasing doses of endotoxin on jejunal absorptive and motor function do not appear to be mediated by changes in blood pressure or heart rate.

Limitations of the anti-idiotype strategy for an HIV vaccine.

Attempts to raise protective immunity to HIV have been notably ineffective. However the conservation of binding of different virus strains to CD4 suggests that the HIV envelope glycoprotein (gp120) should have a conserved site for CD4. Attempts to raise neutralizing anti-idiotypes to CD4 monoclonal antibodies (MoAbs) have generated polyclonal sera which block HIV-induced syncytium formation in vitro but have low titres. Mapping of CD4 epitopes recognized by CD4 MoAbs and gp120 indicates that none of the present CD4 MoAbs bind to exactly the same site as gp120, which may explain the relative lack of success of the anti-idiotype approach to date.

Sequence analysis of an HIV-1 isolate which displays unusually high-level AZT resistance in vitro.

Multiple mutations in the reverse transcriptase (RT) gene were observed in a drug-resistant isolate of human immunodeficiency virus type 1 (HIV1) from an individual having prolonged (greater than 2 years) zidovudine (AZT) therapy. The virus replicated in PBMC's in the presence of very high concentrations of AZT (125 microM). Drug-sensitive strains were curtailed by 0.01 microM AZT. Eleven defined mutations were observed as compared with published sequences of RT for eight strains of HIV1. Eight of these mutations were found in the domain involved in nucleotide recognition and enzyme function. Only one of the mutations, giving a Thr--Tyr change at amino acid 215, matched those previously ascribed (67, 70, 215, and 219) to the generation of high-level resistance to AZT. Therefore additional amino acid changes may have significance in the emergence of super-resistant viruses.