Maternal thyrotropin is independently related to small for gestational age neonates at term.

OBJECTIVE: Small for gestational age (SGA) newborns constitute still a major cause of perinatal morbidity and mortality. Overt thyroid disease is a known cause of preterm birth and low birthweight but in its untreated condition it is rare today. In this study, we investigated the possible relation between maternal thyroid function assessed in euthyroid women at each trimester and the incidence of term born SGA neonates. DESIGN: A prospective cohort study was performed. PATIENTS: Thyroid function was assessed at 12, 24 and 36 weeks gestation in 1051 healthy Caucasian women who delivered at ≥ 37 weeks gestation. MEASUREMENTS: One-way anova was used to compare mean TSH and FT4 levels between women with SGA neonates and controls. Multiple logistic regression analysis was performed to adjust for known risk factors of SGA. RESULTS: Seventy (6·7%) SGA neonates were identified and they were significantly more often born to women with a TSH ≥ 97·5th at first and third trimester. Multiple logistic regression analysis showed that smoking (OR: 4·4, 95% CI: 2·49-7·64), pre-eclampsia (OR: 2·8, 95% CI: 1·19-6·78) and TSH ≥ 97·5th percentile (OR 3·3, 95% CI 1·39-7·53) were significantly related to SGA. Maternal FT4 levels and TPO-Ab status were not associated with SGA offspring. CONCLUSIONS: Our data show that TSH levels in the upper range of the reference interval at different trimesters (3·0-3·29 mIU/l) are independently related to an increased risk of delivering SGA neonates at term.

Neonatal thyroid screening results are related to gestational maternal thyroid function.

OBJECTIVE: To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results. BACKGROUND: Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce. DESIGN/PATIENTS: Prospective follow-up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12-week gestation until term delivery (>37 weeks) and their neonates. MEASUREMENTS: The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)-Ab] assessed at 12-, 24- and 36-week gestation. RESULTS: Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24- and 36-week gestation. Higher maternal TSH levels (>97·5th percentile, as defined in 810 women without TPO-Ab at 12 weeks) at one or more times during pregnancy (O.R: 2·26, 95% CI: 1·20-4·29) and lower gestational age (O.R: 1·22, 95% CI: 1·05-1·41) are independently related to lower screening TT4 levels. CONCLUSIONS: Maternal thyroid function during gestation is related to neonatal TT4 at screening. The finding of both lower neonatal TT4 levels in boys and higher TSH levels in mothers carrying boys is worthy of further investigation, as both observations may be meaningfully related.

High thyrotrophin levels at end term increase the risk of breech presentation.

OBJECTIVE: To study the relationship between maternal thyrotrophin (TSH) and breech presentation at term. DESIGN: Combined data sets of two prospective studies to obtain adequate epidemiological power. PATIENTS: One thousand and fifty-eight healthy pregnant women (58 breech, 1000 cephalic) and 131 women who presented in breech at an obstetrical outpatient clinic. MEASUREMENTS: Maternal thyroid parameters [TSH, free thyroid hormone (FT4), thyroid peroxidase antibody (TPO-Ab)] and foetal presentation were assessed in both groups between 35 and 38 weeks gestation. Power calculations suggested that at least 148 breech cases were required. RESULTS: The characteristics of the women in breech in both samples were similar. Women in breech (n = 58 + 131) had significantly higher TSH (but not FT4) than those (n = 1000) with cephalic presentation (Mann-Whitney U-test, P = 0·003). Different cut-offs were used to define high TSH in the 916 TPO-Ab-negative women with cephalic presentation: the 90th, 95th and 97·5th percentiles were 2·4 mIU/l (n = 149), 2·7 mIU/l (n = 77) and 3·2 mIU/l (n = 37). The prevalence rates of breech presentation in these women were all higher compared to the prevalence of breech in women below these cut-offs (df = 1, P < 0·01). The relative risk of the 149 women with a TSH >90th percentile (>2·4 mIU/l) to present in breech was 1·82 (95% CI: 1·30-2·56). CONCLUSIONS: Women with high TSH at end term are at risk for breech presentation. Substantial evidence for a relation between breech presentation and neurodevelopmental delay exists. As high TSH during gestation has also been linked to poor neurodevelopment, the relation between breech presentation and poor neurodevelopment might be thyroid-related.

Maternal thyroid function during gestation is related to breech presentation at term.

OBJECTIVE: To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. DESIGN: Prospective follow-up study during three trimesters of gestation. PATIENTS: A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery. MEASUREMENTS: Maternal thyroid parameters [TSH, free T4 (FT4) and auto-antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. RESULTS: At term, 58 women (5.5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0.007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH >or= 2.5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4.8% in the women with TSH < 2.50 mIU/l (P = 0.006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (>or=2.5 mIU/l) at 36 weeks gestation (O.R.: 2.23, 95% CI: 1.14-4.39), but not at 12 and 24 weeks gestation. CONCLUSIONS: Women with TSH levels above 2.5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.

[Estimating renal function based on creatinine clearance: application of different formulas and correction for obese patients]. / Schatting van de nierfunctie op grond van de creatinineklaring: bruikbaarheid van enkele formules en correctie bij obese patiënten.

OBJECTIVE: To determine whether glomerular filtration rate (GFR) is best estimated by the Cockcroft-Gault formula or the formula used in the 'Modification ofdiet in renal disease' (MDRD) study. DESIGN: Descriptive inventory. METHOD: Passing-Bablok regression analysis was performed using the statistics program 'Analyse it' for the estimated GFR derived by both formulas based on 467 patients who had data on height, weight and creatinine clearance entered into the laboratory information system of the Máxima Medical Centre, Veldhoven, the Netherlands, during a 2-year period. The performance of each formula was analysed in different patient groups based on weight. RESULTS: The MDRD formula and the Cockcroft-Gault formula performed similarly in all weight groups with adequate precision, particularly when the corrected Cockcroft-Gault formula was used for patients with a body-mass index (BMI) >25 kg/m2. The fact that outcomes using the BMI-corrected Cockcroft-Gault formula strongly correlated with outcomes calculated using the so-called Salazar-Corcoran formula, which was developed specifically for use in obese patients, confirms the validity of the BMI-corrected approach. CONCLUSION: The Cockcroft-Gault formula and the MDRD formula both provided appropriate estimates of GFR and were also considerably more suitable for screening for renal function than assessment of plasma creatinine concentration. However, the best non-invasive way to determine GFR remains a carefully performed assessment ofcreatinine clearance using plasma and 24-hour urine samples.

Multi-antioxidant supplementation does not prevent an increase in gut permeability after lower torso ischemia and reperfusion in humans.

BACKGROUND: An increase in gut permeability can have serious consequences leading to sepsis and multiple organ failure. After lower torso ischemia an increase in gut permeability is seen in both animals and humans. There is proof that this can be modified by antioxidant supplementation. METHODS: In this prospective, randomized study we have looked at the influence of a multiantioxidant supplementation regime, using allopurinol, vitamins E and C, mannitol and N-acetylcysteine, perioperatively. Twenty-two patients received standard treatment and 20 patients received supplementation. Gut permeability was determined using a double sugar test with lactulose and rhamnose. RESULTS: A significant increase in gut permeability was found neither in the non-treatment group (p = 0.012) nor in the treatment group (p = 0.006) after 6 and 24 h. No difference was found between the group receiving antioxidants and the standard treatment group. p = 0.93 6 h post clamp; p = 0.97 24 h post clamp. CONCLUSION: In this study we have not found an influence of multiantioxidant supplementation on gut permeability after lower torso ischemia. Possible explanations for this negative result are being discussed.

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

BACKGROUND: open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. OBJECTIVE: to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. METHOD: forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. RESULTS: WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). CONCLUSION: multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation.

Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?

BACKGROUND: Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion. METHODS: In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance. RESULTS: Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2. CONCLUSIONS: The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.

Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum.

OBJECTIVE: Depression is not adequately diagnosed in many cases. Therefore, the question arises as to whether markers exist for depression. We investigated whether the presence of thyroperoxidase antibodies (TPOAbs) during pregnancy can be regarded as a marker for depression in the first year postpartum, particularly in relation to (overt or subclinical) thyroid dysfunction and other determinants of depression. DESIGN: This work was a prospective observational study. PATIENTS: A cohort of 310 unselected women (residing in the Kempen Region, southeastern Netherlands) were visited at 12 and 32 weeks gestation and at 4, 12, 20, 28 and 36 weeks postpartum. METHODS: At each visit, TSH, free thyroxine and TPOAb testing was performed, determinants associated with depression were asked for, and depression was assessed (according to the Research Diagnostic Criteria). Multiple logistic regression was performed to determine independent risk factors (odds ratios, ORs) for depression in gestation and/or postpartum depression. RESULTS: Data for 291 women were available for analysis; 41 women (14.1%) had TPOAbs at one or more time points, and 117 women (40.1%) had depression at one or more time points postpartum. The multiple logistic regression analysis showed that TPOAbs were independently associated with depression at 12 weeks gestation and at 4 and 12 weeks postpartum (OR, 95% confidence interval: 2.4 (1.1-6.0), 3.8 (1.3-7.3) and 3.6 (1.2-7.1) respectively). After the exclusion of women who were depressed at 12 weeks gestation (n=70), the presence of TPOAbs during early pregnancy was still found to be associated with the development of postpartum depression (OR, 95% confidence interval: 2.8 (1.7-4.5); after exclusion of women who had had depression in earlier life (n=51), TPOAb during early gestation was still associated with postpartum depression (OR, 95% confidence interval: 2.9 (1.8-4.3). CONCLUSIONS: The presence of TPOAbs during gestation is associated with the occurrence of subsequent depression during the postpartum period and as such can be regarded as a marker for depression.

Antioxidants reduce oxidative stress in claudicants.

BACKGROUND: Low-grade ischemia-reperfusion in claudicants leads to damage of local tissues and remote organs. Since this damage is partly caused by oxygen-derived free radicals (ODFR), scavenging these ODFR could reduce the local and remote injury. METHODS: Using a new method by which a free radical reaction product (ortho-APOH) of the exogenous marker antipyrine is measured to quantify the oxidative stress, 16 stable claudicants performed a standard walking test before and after administration of vitamin E (200 mg) and vitamin C (500 mg) daily for 4 weeks. FINDINGS: Ortho-APOH was significantly increased during the reperfusion period (P = 0.026) before administration of the vitamins. After 4 weeks of vitamin supplementation no rise was found in the reperfusion period. Malondialdehyde showed no changes in either group. INTERPRETATION: These findings indicate that administering extra antioxidants to claudicants reduces oxidative stress in these patients. This may also have an effect on the remote ischemia-reperfusion damage and reduce cardiovascular morbidity in this group.

Differences in renal response between endovascular and open repair of abdominal aortic aneurysms.

OBJECTIVES: to determine the difference in renal and systemic response between open and endovascular aneurysm repair. MATERIALS AND METHODS: we studied prospectively 22 patients undergoing open repair (OR) and 15 patients undergoing endovascular repair (ER). Blood and urine samples were taken preoperatively (T0) and before clamping of the aorta or femoral artery (T1) and 5 min (T2), 1 h (T3), 6 h (T4), 24 h (Day 1) and 48 h (Day 2) after declamping. Albumin/creatinin ratio (AC ratio) in urine, serum albumin, serum creatinin, serum C-reactive protein and serum lactate were determined. RESULTS: the urinary AC ratio in ER was significantly lower than in OR (p<0.001). In both groups the rise in urine albumin/creatinin ratio after declamping (T2, T3) was significant (p<0.001). C-reactive protein was raised significantly at day 1 and 2 in both groups (p<0.001) with no difference between the groups. Serum lactate values were significantly higher in OR. There was a significant increase in serum lactate 6 h after declamping in the ER group. CONCLUSIONS: after endovascular repair renal damage is less compared to open repair. There is a significant systemic reaction to the endovascular repair causing mild, short-lasting damage to the kidney. This systemic response is most probably induced by a combination of ischaemia reperfusion injury and the surgical trauma of the procedure. Other possible explanations are discussed.

Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy.

BACKGROUND: Maternal thyroid function during early pregnancy is an important determinant of early fetal brain development because the fetal thyroid is unable to produce any T4 before 12-14 weeks' gestation. Overt maternal hypothyroidism as seen in severe iodine-deficient areas is associated with severely impaired neurological development of the offspring. At present, it is not known whether low free T4 (fT4) levels during pregnancy in healthy women from iodine sufficient areas may affect fetal neurodevelopment. METHODS: Neurodevelopment was assessed at 10 months of age in a cohort of 220 healthy children, born after uncomplicated pregnancies and deliveries, using the Bayley Scales of Infant Development. Maternal TSH, fT4 and TPO antibody status were assessed at 12 and 32 weeks' gestation. Maternal gestational fT4 concentration was defined as an independent parameter for child development. RESULTS: Children of women with fT4 levels below the 5th (< 9.8 pmol/l, n = 11) and 10th (< 10.4 pmol/l, n = 22) percentiles at 12 weeks' gestation had significantly lower scores on the Bayley Psychomotor Developmental Index (PDI) scale at 10 months of age, compared to children of mothers with higher fT4 values (t test, mean difference: 14.1, 95% confidence interval (CI): 5.9-22 and 7.4, 95% CI: 1.1-13.9, respectively). At 32 weeks' gestation, no significant differences were found. In the group of women with the lowest 10th percentile fT4 concentrations at 12 weeks' gestation, a positive correlation was found between the mothers' fT4 concentration and children's PDI scores (linear regression, R: 0.46, P = 0.03). After correction for confounding variables, a fT4 concentration below the 10th percentile at 12 weeks' gestation was a significant risk factor for impaired psychomotor development (RR): 5.8, 95% CI: 1.3-12.6). CONCLUSIONS: Low maternal plasma fT4 concentrations during early pregnancy may be an important risk factor for impaired infant development.

Serum cholesterol decline and depression in the postpartum period.

We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for women who became depressed (n = 63) in the subsequent period and women who did not (difference, 0.10 mmol/l; 95% confidence interval [CI] -0.16 to 0.37). Adjusting for age, multiparity, education level, smoking status, concurrent illness, and social support, the odds ratio of depression was 1.4 (95% CI, 0.64 to 2.9) for women in the highest tertile of serum cholesterol decline and 0.61 (95% CI, 0.28 to 1.3) for women in the intermediate tertile, as compared with women in the lowest tertile. Our results do not support the hypothesis that rapid serum cholesterol decline increases risk of depression in the postpartum period.

Prediction of post partum thyroid dysfunction: can it be improved?

BACKGROUND: Screening pregnant women for thyroid peroxidase antibodies (TPOAb) to identify those at risk for post partum thyroid dysfunction (PPTD) is controversial, mainly because of the low positive predictive value (ppv) of TPOAb. OBJECTIVES: To evaluate if the ppv of TPOAb can be enhanced, either by taking into account the time of TPOAb testing, or by combining this parameter with other putative determinants of PPTD such as smoking, family history or other autoimmune diseases. METHODS: A prospective study was performed in the Kempenland region (southeastern Netherlands). Three hundred and ten unselected women were visited at 12 and 32 weeks gestation and 4, 12, 20, 28 and 36 weeks post partum. Serial thyroid stimulating hormone (TSH), free thyroxine (fT4) and TPOAb testing was performed. Thyroid dysfunction (TD) was defined as abnormal TSH either in combination with abnormal fT4 (overt TD) or without abnormal fT4 (subclinical TD). PPTD was defined as overt TD post partum. Multivariate regression analysis was performed for determining independent risk factors for PPTD. The sensitivity and specificity of TPOAb at different time points and at different concentrations were calculated and presented in receiver operating characteristic (ROC) curves. Women who had experienced PPTD were followed for 2.5-3 years. RESULTS: Data from 291 women were available for analysis. Serum fT4 declined during pregnancy and returned to baseline values post partum. TD in gestation was present in 23 women (7.9%): serum TSH was transiently decreased in 13 (6 had overt gestational thyrotoxicosis (2.1%)) and increased in 10 (2 had TPOAb). Both point prevalence and concentration of TPOAb decreased during gestation and returned to baseline levels within 12 weeks post partum. TD in post partum was present in 36 women (12.4%): 21 had subclinical and 15 overt TD. Out of the 15 women with overt TD (incidence of PPTD: 5.2%) 10 were positive for TPOAb (TPOAb+): 9 had thyrotoxicosis (4 TPOAb+), 5 hypothyroidism (5 TPOAb+) and 1 thyrotoxicosis followed by hypothyroidism (TPOAb+). Independent risk factors for PPTD were TPOAb (relative risk (RR) = 2 7.2), bottle feeding (RR = 11.1) and smoking habits (ever smoked: RR = 3.1; women with PPTD had smoked more cigarettes for a longer period of time). The sensitivity of TPOAb testing was highest at 12 weeks gestation (0.67). The ppv of TPOAb was 0.31-0.75 (depending on time of testing and concentration), increasing slightly to 0.38-0.80 when combined with bottle feeding or smoking habits. There appeared to be an autoimmune form of PPTD in 2/3 of cases and a non-autoimmune form; women with the autoimmune form were at risk for developing permanent hypothyroidism. CONCLUSIONS: A maximum of 2/3 of PPTD cases can be predicted from the presence of TPOAb because 1/3 remained negative for TPOAb. The most appropriate time for TPOAb testing is in the first trimester of pregnancy. The combination of TPOAb testing with anamnestic determinants of PPTD does not increase ppv substantially.

The effect of hysterectomy and endometrial ablation on follicle stimulating hormone (FSH) levels up to 1 year after surgery.

OBJECTIVES: In this study the hypothesis was tested, that in premenopausal patients FSH-levels would rise after 'simple hysterectomy'. As endometrial ablation is not supposed to compromise ovarian bloodflow, there would be no such change in ablated patients. METHODS: Between January 1995 and April 1996, consecutive premenopausal patients with dysfunctional uterine bleeding who were scheduled for hysterectomy or endometrial ablation were asked to participate in the study. Bloodsamples were drawn before surgery, six weeks, six months and one year after surgery. FSH and oestradiol (E2) were assayed. In all patients data about length and weight were collected to calculate Body Mass Index (BMI). Every visit patients filled in a questionnaire, containing questions about typical climacteric complaints, combined in a five-point scale. RESULTS: Except for a significant difference in preoperative FSH-level between both groups, there were no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2) or the percentage of women with vasomotor complaints. Compared to the preoperative starting level, six weeks, six months and one year after surgery a significant rise in serum FSH in the hysterectomy group, as well as in the ablation group was found. However there was no significant difference in FSH increase between both groups. One third of the patients in both groups had typical climacteric complaints as flushing and nocturnal sweating. CONCLUSIONS: Assaying serum FSH-levels before and after uterine surgery and comparing hysterectomized patients and patients after endometrial ablation, we found a significant rise in FSH-level up to one year after surgery in both groups postoperatively, indicating impaired ovarian function. There was no difference in FSH-levels between both groups. Therefore major uterine surgery (hysterectomy, ablation) may prelude an earlier onset of menopause.

Cell-mediated immunity and postpartum thyroid dysfunction: a possibility for the prediction of disease?

Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an autoimmune (AI) destruction of thyroid follicles during the pp period. The chronic thyroid AI process [already present in pregnancy, as shown by the positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes overt disease in the pp period, and one assumes that this exacerbation represents a rebound phenomenon after a general immunosuppression during pregnancy. The presence of TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development. Apart from B cells, e.g. production of autoantibodies, various functions of the cell-mediated immune (CMI) system, including those of peripheral T cells, monocytes, and dendritic cells (DC), are also disturbed in AI states. The objectives of the present study were: determining alterations in various CMI parameters in pregnancies followed by PPTD vs. those not followed by PPTD; and determining the usefulness of these parameters in the prediction of PPTD. In a prospective study (region: Kempenland, southeast Netherlands), a random sample of 291 women were tested at 12 and 32 weeks gestation and 4 weeks pp for TPO-Ab. Women were followed until 9 months pp, for developing PPTD. PPTD was defined as both: an abnormal TSH, and fT4 pp women developing PPTD and/or being positive for TPO-Ab (n = 26); and thyroidological uneventful control women of the same cohort, matched for age and parity (n = 21), were tested for thyroid-stimulating antibodies, percentages of peripheral blood lymphocyte subsets using fluorescence-activated cell sorter analysis (CD3, CD4, CD8, CD16, CD56, major histocompatibility complex-class II), for monocyte polarization, and for cluster capability of monocyte-derived DC. Results were: 1) 31 women (10.7%) were positive for TPO-Ab (TPO-Ab+) in gestation (12 and/or 32 weeks); 2) 15 women (5.2%) developed PPTD, of whom 10 were TPO-Ab+ in gestation; 3) pregnancy-related CMI alterations consisted of low percentages of CD16+CD56+ natural killer (NK), cells and a low DC cluster capability at 12 weeks gestation (these functions were normalized at 32 weeks gestation); 4) the TPO-Ab+ PPTD+ women (4 hyper, 5 hypo, and 1 hyper/hypo) were characterized by a persistently low percentage of NK cells, a lowered monocyte polarization, and a raised percentage of major histocompatibility complex-class II+CD3+ T cells; 5) the TPO-Ab- PPTD+ women (all 5 hyper) had neither thyroid-stimulating antibodies nor CMI alterations, apart from those normally seen in pregnancy; 6) 21 women were positive for TPO-Ab in pregnancy but did not develop PPTD (they had the same lowered NK cell percentages and monocyte polarization as the TPO-Ab+ PPTD+ cases, but they had normal percentages of activated peripheral T cells and a lower titer of TPO-Ab); 7) determination of the number of NK cells and monocyte polarization hardly contributed to the prediction of PPTD (as compared with TPO-Ab status), because of strong interindividual variation and close association with the presence of TPO-Ab; and 8) combining TPO-Ab assays with testing for activated T cells was the most optimal parameter for the prediction of TPO-Ab+ cases of PPTD in our small test set. We conclude that TPO-Ab+ pregnant women who develop PPTD show several CMI abnormalities other than those seen in normal pregnant women, such as persistently lower percentage of NK cells, a lowered monocyte polarization, and a raised percentage of activated T cells. The latter seems rather specific for the actual PPTD development and is not found in TPO-Ab+ (but PPTD) uncomplicated pregnancies. TPO-Ab- (but PPTD+) women had no signs of CMI abnormalities (apart from those specific for the pregnancy state). Although studied cases are low in number, our data are suggestive for the existence of two forms of PPTD: a TPO-Ab+ (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab- (non-AI) form (one-third of patients, only hyper). Such assumption implies that, at best, two

Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?

Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly microsomal antibodies (MsAb)] are at particular risk for developing postpartum thyroid dysfunction; the latter is significantly associated with postpartum depression. Although the negative effect of postpartum maternal depression on child development is well documented, the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known. In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development.

Four agglutination assays evaluated for measurement of von Willebrand factor (ristocetin cofactor activity)

The concentration of von Willebrand factor (vWf) in patients' plasma can be determined by measuring the ristocetin cofactor activity (vWf R:Co). However, this vWf R:Co assay is time consuming, which limits its routine use. Several commercial vWf R:Co tests, based on agglutination of lyophilized fixed platelets, are available. We evaluated the slide tests and aggregometer assays from Behring and Organon Teknika and compared them with the classic vWf R:Co aggregometer method. The within-run and between-run precisions of the two slide tests were better than those of the aggregometer methods. The correlation studies between the four commercial assays and the classic aggregation method were based on 23 plasma samples (range: 15-450% vWf R:Co). The correlation coefficients, which ranged from 0.923 to 0.950, did not differ significantly (P > 0.1). All four commercial assays gave significantly lower vWf R:Co values than the classic aggregation method (P < 0.01). We conclude that commercially available fixed platelets can be used for the rapid measurement of vWf R:Co with a slide test. The use of the aggregometer is time consuming and may result in a lower precision.

[Latex hypersensitivity, an increasing problem]. / Latexallergie, een toenemend probleem.

As a result of the frequent use of rubber containing products in medical health care, latex allergy is becoming an increasing problem. Based on a case history of a hospital employee, this paper will discuss the cause and consequences of this specific allergy.

Androgen turnover during marathon running.

The purpose of the study was to investigate the effect of prolonged physical stress on peripheral androgen turnover. Venous blood samples were taken from 18 athletes 24 h before finishing a competitive marathon run and directly after running the race. Serum cortisol, testosterone (T), dehydroepiandrosteronesulfate (DHEAS), sex hormone binding globulin (SHBG), and 5 alpha-androstane- 3 alpha, 17 beta-diolglucuronide (3 alpha-AdiolG) were determined and corrected for hemoconcentration. Marathon running caused a rise in serum cortisol concentration in all athletes. Furthermore, a significant (P < 0.01) rise in serum T and T-index (index of free T) was observed. The significant (P < 0.01) rise in serum DHEAS concentration, a mainly adrenal cortical androgen, pointed toward a stimulation of the adrenal cortex or a reduced hepatic metabolic clearance rate. Finally, 3 alpha-AdiolG, an androgen metabolite exclusively formed in peripheral tissues, was increased in the sera of all athletes. These results suggest that marathon running leads to increased concentrations of serum adrenal and gonadal androgens. The simultaneously increased 3 alpha-AdiolG levels may be caused by increased androgen turnover in peripheral tissues containing 5 alpha-reductase.