Grant award program partnerships with your professional liability insurance carrier: an innovative approach to loss prevention and improved patient safety.

The financial success of a malpractice insurance program is directly influenced by how effectively the covered providers respond to risk. This article describes a University Self-Insurance Program partnership to provide small grants to providers who have the expertise and passion for a specific risk reduction activity that is cost effective and measurable and has a high probability of improving patient care and reducing claims or lawsuits. Implementation of this small grant concept can be tailored to become operational in virtually any setting from an independent medical practice to a multistate healthcare system.

MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction.

The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24-28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r(2)=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development.

Elevated brain weight/liver weight ratio in normal body weight centile term perinatal deaths: an indicator of terminal intrauterine malnourishment.

A proportion of antepartum/intrapartum intrauterine deaths (IUDs) with normal or elevated body weight (BW) centile also show an elevated brain weight/liver weight (BLR) ratio. We postulate that this may be an indication of intrauterine malnourishment/incipient intrauterine growth restriction (IUGR), which may have a bearing on the cause of death. Searching our departmental postmortem database, we identified 331 IUD/intrapartum deaths (254; 77%) or early neonatal deaths (77; 23%), ≥37/40 weeks gestation in a 4-year period. The customized BW centile, BLR, brain weight/thymus weight ratio (BTR), fetus weight/placenta weight ratio (FPR), and maternal body mass index were calculated. A BLR >4.0 and a BTR >60 were regarded as abnormal. Of the 331 cases, the BLR was >4.0 in 71 (21.4%). Nineteen (26.7%) of the 71 had a BW above the 25th centile, and these were all IUDs. Eight deaths were explained. In the 11 unexplained deaths, the BTR was raised in 5 and FPR was elevated in 7. Three of these 11 mothers had impaired glucose tolerance, and 7 were overweight or obese. In the absence of a definitive cause, a raised BLR in an IUD with a normal BW centile is likely to indicate nutritional impairment/incipient IUGR. The majority of these deaths are associated with maternal obesity, with or without impaired glucose tolerance. Recognition of features of IUGR in IUDs of normal BW may help us understand the death. In these cases, placental growth may be insufficient to support a macrosomic fetus, leading to late nutritional impairment and death.

Implementation and experience of an alternative QF-PCR and MLPA diagnostic strategy to detect chromosomal abnormalities in fetal and neonatal pathology samples.

Chromosomal abnormalities are a significant cause of pregnancy loss. Solid tissue fetal and neonatal pathology samples are routinely examined by karyotype analysis after cell culture. However, there is a high failure rate, and this approach is expensive and labor intensive. We have therefore evaluated a new molecular strategy involving quantitative fluorescent polymerase chain reaction (QF-PCR) and subtelomere multiplex ligation-dependent probe amplification (MLPA) analysis. A retrospective audit showed that less than 4% of abnormal cases may not be detected by this molecular strategy. We validated this strategy in parallel with cytogenetic analysis on 110 patient samples, which included cases of fetal loss, still birth, neonatal death, termination of pregnancy, recurrent miscarriage, and sudden unexpected death in infancy. This validation showed that 55 of the 57 samples that gave a result for both strategies were concordant. During the 1st year of diagnostic testing, we analyzed 382 samples by the molecular strategy. A 16% abnormality rate was observed. These included trisomies 13, 18, 21, monosomy X, and triploidy detected by QF-PCR (77%), and 23% were other trisomies and subtelomere imbalances detected by MLPA. This strategy had a 92% success rate in contrast to the 20%-30% failure rate observed with cell culture and cytogenetic analysis. We conclude that QF-PCR and subtelomere MLPA is a suitable strategy for analysis of the majority of fetal and neonatal pathology samples, with many advantages over conventional cytogenetic analysis.

Diversity of neuromuscular pathology in lethal multiple pterygium syndrome.

Lethal multiple pterygium syndrome (LMPS) is an uncommon fetal-onset disorder of unknown etiology. The pathogenesis of LMPS has been suggested to be early-onset fetal akinesia, fragile collagen, or generalized edema. Information on the neuromuscular pathology of LMPS in the literature is generally scanty. We present the findings from a review of 14 fetuses with features of LMPS from the archives of the Hammersmith Hospital Perinatal Pathology Department. Autopsy reports, photographs, fetograms, and histological sections were examined, and additional special stains and immunostaining were performed on muscle sections. In five cases, there was evidence of autosomal recessive inheritance. One case was later shown to be due to glycogen storage disease type IV. The skeletal muscle bulk was reduced in all fetuses and the remaining muscle showed a range of histological appearances including vacuolar degeneration, dystrophy, a generalized or patchy myotubular appearance, and generalized hypotrophy. In one, the histological appearance was essentially normal. Two cases had abnormalities in the brain. Large motor neurons were present in the anterior spinal horns of all fetuses in whom the spinal cord could be examined. There was no evidence of cartilaginous joint fusion. We conclude that LMPS is the phenotype resulting from fetal akinesia commencing in the first or early second trimester. In the majority of cases, the precise underlying cause will not be identified, however, occasionally a metabolic or neurodevelopmental disorder or a specific primary myopathy may be demonstrated, providing adequate autopsy investigations are undertaken.