Protective medical legislation deficient knowledge of maternity (health and safety) rights for work-adjustment exists amongst flexible trainee doctors: is there a risk to maternal and foetal health?

OBJECTIVE: To assess awareness, identify knowledge source and evaluate uptake amongst doctors of "health and safety rights" (HSR) contained within the current European protective medical legislation for pregnant workers. STUDY DESIGN: A descriptive cross-sectional pilot study, by a postal questionnaire during the period 1998-1999, targeted 97 UK doctors (West Midlands region) after their first pregnancy. RESULTS: Of 67 respondents (response rate 73%), 41 (61%) were Registrars (SpR) and 25 (37%) SHOs: 80% work-schedules did not change during pregnancy. Only 11% (95% CI, 4-21%) of the doctors surveyed actually knew their maternity rights. 66.2% had no knowledge of maternity legislation; 80% of respondents had not taken up health and safety rights. Fifty-two percent (95% CI, 40-65%) reported maternal and neonatal complications. CONCLUSIONS: In a self-selected group of flexible trainees following their first pregnancy, only one in five female doctors have adequate knowledge about the legislative "health and safety rights" of work-schedule adjustment. A combination of reasons may contribute to the low uptake of these rights. The question of whether or not poor knowledge and uptake of legislative rights may be detrimental towards pregnancy and neonatal complications requires a large prospective study. An improvement in the knowledge of current maternity legislation could occur by targeting all medical students, all doctors, postgraduate trainers and National Health Service (NHS) employers.

Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?

We report a case of neonatal symptoms of irritability, increased tonus and convulsions after in-utero exposure to paroxetine 30 mg/day. The infant's symptoms commenced on the first day after birth and persisted for 10 days. Paroxetine levels were undetectable on day 6. Extensive investigations excluded infective and metabolic causes. Serotonin toxicity due to paroxetine seems the most likely mechanism, though an important differential diagnosis is a paroxetine discontinuation (withdrawal) syndrome. Differentiating between these two syndromes in the neonate presents a dilemma for clinicians. Irrespective of the mechanism, we recommend that all neonates exposed to antidepressants, particularly serotonin reuptake inhibitors (SSRIs), during the last trimester should be followed-up closely for adverse symptoms commencing in the first 10 days after birth. The possibility of such symptoms needs to be discussed with women who are considering starting or continuing antidepressant treatment in pregnancy. All neonatal adverse drug events should be reported to a pharmacovigilance centre. Further research is warranted.

Distribution analysis of vitamin D highlights differences in population subgroups: preliminary observations from a pilot study in UK adults.

There is no consensus between Authors on the definition of a replete or deficient vitamin D state. Our aim was to describe a suitable method that could be used to compare vitamin D data in subject groups with small or large numbers. Two hundred and forty indigenous asymptomatic, non-pregnant adult subjects recruited from a single-consultation outpatient attendance with normal biochemistry, represented a sample of our inner city district population. 25-hydroxyvitamin D (25,OHD3) levels were measured to illustrate the effects of season, sex and ethnic group on vitamin D levels and subjected to distribution analysis. This method quantifies as a percentage the distribution of 25,OHD3 concentrations (observed concentration, OC) in pooled group data. The data can be expressed as distribution frequency domains or cumulative frequency ogives (0-100%) or transformed into discrete linear probits, amenable to regression analysis. An estimate of the OC50 (mid-point) and upper (either OC75 or OC95) or lower (either OC25 or OC5) range or at any other frequency between subject groups can be compared. A marked difference in 25,OHD3 levels between Asian and non-Asian asymptomatic adult subjects was seen during both seasons. 25,OHD3 deficiency was defined as at or below the OC25 for the non-Asian group (for both sexes: winter < 13.36 ng/ml, summer <13.38 ng/ml). The majority of Asians of both sexes were 25,OHD3 deficient (winter 94%, summer 82%). The distribution analysis provides an easy technique to compare 25,OHD3 status of different subject groups, allowing the description of populations using either longitudinal or cross-sectional data. This method may offer a way of describing 25,OHD3 deficiency between observers worldwide.

Vitamin D deficiency in UK Asian families: activating a new concern.

Vitamin D has steroid hormonal effects which can produce clinical symptoms and signs unrelated to calcium homoeostasis. Its deficiency has been implicated as a risk factor for diabetes, ischaemic heart disease, and tuberculosis in Asians. In this review, the incidence, aetiology, prevention, and treatment of symptomatic vitamin D deficiency in childhood are considered. A renewed public health campaign is required in the UK to address the continuing problem of vitamin D deficiency in Asian families.

Frontal horn thin walled cysts in preterm neonates are benign.

BACKGROUND: Screening cranial ultrasound led to the discovery of isolated frontal horn cysts quite distinct from periventricular leucomalacia cysts. AIM: To clarify their significance, incidence, characteristics, causal factors or aetiology, and effect on long term outcome. DESIGN: A retrospective observational study of all first cranial ultrasound scans (total of 2914) performed during the period 1984-1994 inclusive found 21 neonates with smooth thin walled frontal horn cysts: 18 of 2629 scanned were of birth weight < 1500 g or gestation < 33 weeks, and three of 285 were > 33 weeks gestation. Sequential ultrasound, maternal records, and neonatal events were retrospectively assessed. In survivors, routine neurodevelopmental evaluations were obtained. Postmortem studies of one cyst were performed to determine the nature and origin of these lesions. RESULTS: Of the 21 subjects, 15 had isolated frontal horn cysts and six had additional ultrasound scan abnormalities, including four with subependymal haemorrhage. The sonographic features of frontal horn cysts were of distinctive morphology (elliptical, smooth, thin walled, ranging in size from 3 to 20 mm) and position (adjacent to the tip of the anterior horns). The cysts enlarged and then regressed by a median corrected age of 2 months. Subjects of < 33 weeks gestation (n = 18) had a median birth weight of 1465 g (range 720-1990) and median gestation of 30 weeks (range 24-32). There was no consistent perinatal course. The neurodevelopmental outcome in 10 of the 11 survivors with isolated frontal horn cysts was normal. Five subjects died from causes unrelated to brain pathology in the neonatal period, and one subject died after infancy. Histological examination of a cyst at autopsy in one additional subject subsequent to the period of study confirmed the cyst to be lined by neuroblasts and ependymal cells. CONCLUSIONS: The incidence of frontal horn cysts in this low birthweight population was 7 per 1000 (0.7%) subjects scanned. They are present in the first week of life, enlarge, and resolve spontaneously. Survivors with isolated frontal horn cysts appear to have normal neurodevelopmental outcome. The prognosis of these distinct frontal horn cysts therefore appears to be benign.

Airway obstruction by a child's pacifier--could flange design be safer?

UNLABELLED: The use of pacifiers (dummies or soothers) for infants is prevalent. Rare episodes of an adverse consequence must be taken seriously. We report a case of aspiration of a pacifier by a 6-month-old baby. Nine similar cases were found in the literature since 1966. The details of these cases are outlined and changes to flange design proposed ahead of a new European Union Standard document. CONCLUSION: Pacifier ventilation holes are essential, flanges should have a minimum horizontal and vertical diameter of 43 mm. Rings should be attached to the flange to facilitate removal if aspirated.

Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescents.

OBJECTIVE: To determine the relative effects of growth hormone and insulin on ketogenesis during puberty. RESEARCH DESIGN AND METHODS: We studied overnight changes in plasma ketones--3-hydroxybutyrate and acetoacetate--in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release. RESULTS: Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 +/- 5 microM), reaching a peak at 0200 (103 +/- 16 microM, P < 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = -0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate. CONCLUSIONS: We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.

The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short-term euglycaemia.

OBJECTIVE: High overnight plasma growth hormone (GH) levels in insulin-dependent diabetes mellitus (IDDM) are reflected in both an increase in the GH pulse amplitude and elevated baseline GH concentrations. To determine whether these are a result of an increase in GH secretory episodes, we undertook deconvolution analysis of overnight GH profiles using previously determined half-life data. DESIGN: Deconvolution of overnight GH profiles (2000-0800 h) was undertaken from normal and diabetic adolescents (either on their usual insulin regime (n = 15), during overnight euglycaemic clamp using a variable rate insulin infusion (n = 29), or during clamp plus 100 mg pirenzepine to suppress endogenous GH (n = 7)). PATIENTS: Thirty-five normal and 29 diabetic adolescents of both sexes at all stages of puberty. MEASUREMENTS: GH secretory rates were calculated from deconvolution analysis, and Fourier transformation was increased mean overnight GH secretion when analysed by sex and by puberty stage compared to normal subjects; overnight GH secretion median (range) of diabetic group 1.88 (0.56-3.81) mU/min; control group 0.62 (0.32-1.92) mU/min (P < 0.001). Fourier transform analysis of these secretory episodes showed greater pulse frequency in the diabetics with dominant pulse periodicity of 90 minutes compared with 135 minutes in normal subjects. During overnight euglycaemia, mean +/- SEM overnight GH secretory rates were comparable to subjects' usual regime night (1.82 +/- 0.33 vs 1.91 +/- 0.37 mU/min) and there was no change in the dominant pulse periodicity of 90 minutes. Pirenzepine administration in diabetic subjects significantly reduced overnight GH secretion from 1.57 +/- 0.19 to 0.71 +/- 0.80 mU/min (P < 0.001) showing a median (range) reduction of 63 (9.3-82.8)% when compared to the subjects' clamp night. However, dominant pulse periodicity was not altered by pirenzepine administration, and remained at 90 minutes. CONCLUSION: In patients with insulin-dependent diabetes mellitus there is an increase in both the amplitude and frequency of pulsatile GH secretion compared to normal subjects, which is not affected by maintenance of overnight normoglycaemia. The anticholinergic drug pirenzepine appears to suppress the amplitude of GH pulse secretion but has no effect on frequency.

Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus.

Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

OBJECTIVE: To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates. DESIGN: In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS: Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study. RESULTS: Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001). CONCLUSIONS: The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.