Increase in impaired motor coordination in six-year-old German children between 1990 and 2007.

AIM: To evaluate changes in prevalence of impaired motor coordination among 6-year-olds of a geographically defined area in Germany between the years 1990 and 2007. METHODS: Data from the obligatory school entrance examinations in the German state of North Rhine Westphalia between the years 1990 and 2007 were used. The number of children assessed per year varied from 81 517 to 124 086. The classification of impaired motor coordination was based on the combination of standardized screening and physicians' clinical impression of need of treatment. Logistic regression modelling was performed to evaluate the changes in prevalence of impaired motor coordination. RESULTS: Between 1990 and 2007, the prevalence of impaired motor coordination rose from 2.5% to 8.9% in boys and from 0.8% to 3.6% in girls. As the standard error of these percentages is below 0.15%, the changes are highly statistically significant. CONCLUSION: The prevalence of impaired motor coordination tripled during the last decades in North Rhine Westphalia. This may imply that the prevalence of Developmental Coordination Disorder also increased. Factors that may explain the increasing prevalence include the increase in surviving preterm infants, increasing parental age at child birth, maternal and child obesity and decreasing child mobility.

The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy.

BACKGROUND: Due to the growing number of children born following assisted reproduction technology, even subtle changes in the children's health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children. METHODS: In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development. RESULTS: The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups. CONCLUSIONS: We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

The predictive value of ovarian reserve tests for miscarriage in a population of subfertile ovulatory women.

BACKGROUND: The increase in miscarriage rate with female age is attributed to a decline in oocyte quality. This age-related decrease of oocyte quality is accompanied by a decrease in oocyte quantity. Assessment of the number of oocytes by ovarian reserve tests (ORTs) may therefore also represent their quality. The objective of our study was to assess the predictive value of ORTs for miscarriage in subfertile women. METHODS: This study was a subanalysis within a prospective cohort study of 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), basal and stimulated levels of follicle-stimulating hormone (FSH) and inhibin B, and the clomiphene citrate challenge test (CCCT). Women who achieved an ongoing pregnancy (n = 233) were compared with women experiencing miscarriage (n = 72) on the results of their ORTs and patient characteristics. RESULTS: In univariate analysis, the outcome of the ORTs did not differ between the groups. Logistic regression analysis including patient characteristics such as female age did not reveal an association between the ORT results and miscarriage either. CONCLUSIONS: Neither AFC, basal and stimulated levels of FSH and inhibin B, nor the CCCT have a statistically significant predictive value for miscarriage in subfertile ovulatory women.

The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women.

BACKGROUND: The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. METHODS: A prospective cohort study was performed on 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), follicle-stimulating hormone (FSH), inhibin B (basal levels and after stimulation with clomiphene citrate) and the clomiphene citrate challenge test. For each couple, the probability of spontaneous pregnancy was retrospectively calculated using the validated Hunault prediction model which includes the main known prognostic factors for spontaneous pregnancy. Outcome measure was time to spontaneous pregnancy resulting in a live birth. RESULTS: When added to the Hunault model, only basal FSH and AFC significantly improved the prediction of spontaneous pregnancy (P-values of 0.05 and 0.04). Absolute changes in predicted probabilities after adding basal FSH or AFC were small: the predicted probability of spontaneous pregnancy shifted >or=10% in only 3.8% and 7.9% of the couples, respectively. CONCLUSIONS: Although basal FSH and AFC significantly improved the validated prediction model for spontaneous pregnancy, the clinical relevance of this finding is limited. We recommend that none of the ORTs studied should be used routinely in the subfertility evaluation of ovulatory couples to predict spontaneous pregnancy chances.

Approximal secondary caries lesion progression, a 20-week in situ study.

There is no consensus about the definition and progression of outer and wall lesions in secondary caries. In this study we investigated whether lesion progression is influenced by an adjacent composite restoration and whether wall lesions develop at the composite-tooth interface. In order to study the appearance and progression of approximal primary caries lesions and lesions next to composite restorations, 16 samples were placed in a full denture of each of 8 subjects. Each denture housed 4 restored and 4 unrestored enamel samples and similarly 8 dentin samples. All samples were distributed over 2 sample holders, in each of which 4 approximal spaces were simulated. Every 4 weeks the sample holders were microradiographed using transversal wavelength independent microradiography and lesion depth was measured. At the end of the study, after 20 weeks, the lesion depth of the outer lesions was 0-350 microm for enamel and 0-750 microm for dentin. The estimated difference in progression between secondary and primary lesions (1.1 microm/4 weeks, 95% CI: -9.2 to 11.4 microm) was not statistically significant (p = 0.83). Secondary outer lesions appeared and progressed as primary caries lesions. No clear wall lesions were found next to composite, but they were observed next to acrylic resin.

Blood viscosity and uterine artery flow velocity waveforms in pregnancy: a longitudinal study.

In the course of pregnancy, whole blood viscosity (WBV) decreases, plasma viscosity (PV) increases and uteroplacental resistance to blood flow falls. According to the Hagen-Poiseuille law, viscosity influences resistance to blood flow. To investigate the contribution of these haemorheological changes to the decrease in resistance to blood flow in the uteroplacental circulation, a serial study was performed. Using blood viscosimetry and pulsed Doppler ultrasound recordings of the uterine arteries, 21 women with normal pregnancies were studied every 8 weeks from 12 weeks onwards. Statistical analysis revealed no significant relationship between WBV, PV and pulsatility index of the uterine arteries. It is concluded that the changes in blood viscosities are of minor influence on resistance to blood flow in the uteroplacental circulation throughout normal pregnancy. The vascular changes e.g. the considerable increase of the diameter of the spiral arteries have a much greater impact on resistance to blood flow.

Oropharyngeal flora as a source of bacteria colonizing the lower airways in patients on artificial ventilation.

During 1 year 27 patients admitted to the respiratory intensive care unit were monitored bacteriologically for a minimum of 10 days (mean: 26.7 days). Oropharyngeal swabs and tracheal aspirates were qualitatively and semi-quantitatively cultured twice weekly. A correlation between oropharyngeal and tracheal flora was found: once a bacterial species colonized the oropharyngeal cavity in high numbers, the identical microorganism was frequently isolated (greater than 50%) from the lower respiratory tract. Six of the 27 patients acquired an infection of the lower airways in the respiratory intensive care unit. The bacteria involved belonged to the patients oropharyngeal flora: S. aureus, Enterobacteriaceae and Pseudomonadaceae. As a result of this study showing the oropharynx to be the source of lower airway colonization/infection, a policy for infection prevention has been outlined. This policy is based on the concept of source elimination by means of oropharyngeal decontamination.

Colonization of burns and the duration of hospital stay of severely burned patients.

In a retrospective study the influence of several factors on the length of hospital stay of severely burned patients (at least 24% total body surface area) has been investigated. The influence of these factors was studied by means of the Cox model survival analysis with time-varying covariates. Seventy-one patients were included in this study. The mean age was 32 years (range 1-82 years), the mean total body surface area burned 40% (range 24-80%) and the mean full-thickness area burned 32% (range 10-70%). The length of hospital stay was positively correlated with the extent of the burned area and with the age of the patient. Wound colonization with Enterobacteriaceae or with a combination of Pseudomonas spp. and Staphylococcus aureus was also associated with a prolonged stay in hospital.

Fitting multistate transition models with autoregressive logistic regression: supervised exercise in intermittent claudication.

The purpose of this study was to develop a model that predicts the outcome of supervised exercise for intermittent claudication. The authors present an example of the use of autoregressive logistic regression for modeling observed longitudinal data. Data were collected from 329 participants in a six-month exercise program. The levels of the polytomous outcome variable correspond to states they defined in a Markov decision model comparing treatment strategies for intermittent claudication. Autoregressive logistic regression can be used to fit multistate transition models to observed longitudinal data with standard statistical software. The technique allows exploration of alternative assumptions about the dependence in the outcome series and provides transition probabilities for different covariate patterns. Of the alternatives examined, a Markov model including two preceding responses, time, age, ankle brachial index, and duration of disease best described the data.

The relation between umbilical pH values and neonatal neurological morbidity in full term appropriate-for-dates infants.

The relationship of umbilical cord pH with the neonatal neurological condition was investigated in a group of 805 appropriate-for-dates (AFD) infants, delivered vaginally at term, and in a subgroup of 205 infants born after uncomplicated pregnancy and delivery ('low-risk' group). The results of the neonatal neurological examination were expressed in a neonatal neurological optimality score (NNOS) and in a neurological classification (normal, suspect and abnormal). In both study groups a significant relation between umbilical arterial pH (pHua) and the difference between maternal venous pH and pHua (delta pHm-ua) on the one hand and neurologically suspect infants and NNOS on the other hand, was found. The percentages of explained variance in NNOS, however, were very low (for delta pH, 1 and 4% in the total and low-risk group respectively). Neurological abnormality was not related to acidaemia at birth. Because of the specific relation between maternal and umbilical pH, delta pH is a less reliable indicator of fetal condition in cases of maternal alkalosis or acidosis. The use of a delta pH corrected with the help of a maternal-fetal pH nomogram, however, only slightly improved the relation with neurological morbidity. It is concluded, that in AFD term infants acidaemia at birth is only slightly related to neonatal neurological morbidity.

Neurological condition in 42-month-old children in relation to pre- and postnatal exposure to polychlorinated biphenyls and dioxins.

Adverse neurological effects of exposure to PCBs have been found up to 18 months of age. Now we report on the effect of pre- and postnatal exposure to PCBs and dioxins on the neurological condition at 42 months of age. For this purpose, PCB levels were determined in cord and maternal plasma, and used as a measure of prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition, PCBs were determined in plasma sampled from the child at 42 months of age. We evaluated the neurological condition of 394 children using the Touwen/Hempel method. After adjustment for covariates, neither prenatal PCB exposure nor postnatal exposure to PCBs and dioxins was found to be related to the neurological condition at 42 months of age.

Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development.

Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs)) are widespread environmental contaminants which are neurotoxic in animals. Perinatal exposure to PCBs, PCDDs, and PCDFs occurs prenatally via the placenta and postnatally via breast milk. To investigate whether such an exposure affects the neonatal neurological condition, the neurological optimality of 418 Dutch newborns was evaluated with the Prechtl neurological examination. Half of the infants were breast-fed, the other half were formula-fed, representing a relatively high against a relatively low postnatally exposed group, respectively. As an index of prenatal exposure, four non-planar PCBs in cord and maternal plasma were used. These PCB levels were not related to neurological function. As measures of combined pre- and early neonatal exposure, 17 dioxin congeners, three planar, and 23 non-planar PCB congeners were determined in human milk in the second week after delivery. Higher levels of PCBs, PCDDs, and PCDFs in breast milk were related to reduced neonatal neurological optimality. Higher levels of planar PCBs in breast milk were associated with a higher incidence of hypotonia. This study confirms previous reports about the neurotoxic effects of these compounds on the developing brain of newborn infants.

Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins.

The neurological optimality of 418 Dutch children was evaluated at the age of 18 months, in order to determine whether prenatal and breast milk mediated exposure to polychlorinated biphenyls (PCBs) and dioxins affected neurological development. Half of the infants were breast-fed, the other half were formula-fed. PCB concentrations in cord and maternal plasma were used as a measure of prenatal exposure to PCBs. To measure postnatal exposure, PCB and dioxin congeners were determined in human milk and in formula milk. After adjusting for covariates, transplacental PCB exposure was negatively related to the neurological condition at 18 months. Although greater amounts of PCBs and dioxins are transferred via nursing than via placental passage, an effect of lactational exposure to PCBs and dioxins could not be detected. We even found a beneficial effect of breast-feeding on the fluency of movements. We conclude that transplacental PCB passage has a small negative effect on the neurological condition in 18-month-old toddlers.

Preterm birth, growth retardation and acidemia in relation to neurological abnormality of the newborn.

The Groningen Perinatal Project is a follow-up study relating pre- and perinatal conditions to early and late neurological sequelae. A description is given of the first cohort of 1507 children, examined neurologically during the neonatal period, and of their mothers and their pregnancies. In this preliminary analysis three 'final pathways' are considered, i.e. intrauterine growth retardation, preterm birth and acidemia (pH in umbilical vein below 7.20). Significant relationships were found between the 'final pathways' and the neurological findings. Since, however, these relationships account for only a small part of the variance of the latter, it is concluded that the (cumulative) effect of other antenatal variables must be taken into account as well. Results of analyses to this effect will be reported in forthcoming publications.

Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma.

AIM: In spite of extensive use of 131I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. PATIENTS AND METHODS: 30 consecutive patients were treated with 925 MBq 131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131I. RESULTS: After application of 131I no clinical worsening was observed. FT4 and fT3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p < 0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. CONCLUSION: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by 131I induced necrosis of thyroid cells was found. Therefore, the application of 131I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma.

Early changes of thyroid hormone concentrations after (131)I therapy in Graves' patients pretreated or not with methimazole.

AIM: Despite extensive use of (131)I therapy for Graves' hyperthyroidism the treatment regimen with (131)I and antithyroid drugs remain under discussion. In our prospective clinical study we followed acute thyroid hormone changes after (131)I in patients not pretreated with methimazole (MMI) and in patients with different MMI pretreatment regimens. PATIENTS, METHODS: 187 patients were treated with fixed activity of 550 or 740 MBq of (131)I. First group (71 patients) received (131)I alone. In the second group (57 patients) MMI was stopped seven days before (131)I. The third group (59 patients) received MMI until (131)I application. Initial free triiodothyronin and free thyroxin were measured in the second group 7 and 2 days before (131)I therapy and in all three groups on the day of (131)I application as well as 2, 5, 12, and 30 days afterwards. Absorbed dose was measured in each patient. RESULTS: In the non-pretreated group (131)I application was followed by a significant decrease of fT4 in 5 days and of fT3 in 2 days, higher reduction was detected in patients with higher baseline values. In MMI pretreated patients significant but clinically irrelevant increase of both thyroid hormones was detected with maximum value 7 days after discontinuation in the second group and 5 days after discontinuation in the third group. Additionally, in patients of the third group absorbed dose of (131)I was significantly lower relative to other two groups. We found no correlation between absorbed dose of (131)I and thyroid hormone changes. CONCLUSION: Our study demonstrates that (131)I application alone does not result in exacerbation of hyperthyroidism and therefore it may be considered as safe. Additionally, MMI withdrawal causes significant but clinically irrelevant elevation of thyroid hormones.

Study of myocardial regional wall motion parameter's accuracy by software perfusion phantom.

Gated perfusion myocardial scintigraphy permits simultaneous evaluation of perfusion as well as regional contractile function of the left ventricle. Fourier analysis of regional myocardial spatial movement with respect to the myocardial geometric centre gives circular amplitude and phase profiles of ventricular contraction, in addition to regional maximum activity that represents an index of perfusion. To introduce such combined perfusion-contraction analysis the accuracy of the indices mentioned above should be evaluated for different doses of radioactivity typically administered to a patient. A mathematical software phantom, consisting of a half circularly profiled ring activity embedded in uniform background activity and noise generated by a Poisson-shaped random number generator, was constructed and used for this purpose. A 64 x 64 matrix and sequence of 16 frames per study was used. The maximum number of counts per pixel ranged from 10 to 100, simulating low count thallium and high count rate Tc-MIBI-gated studies. The relative standard error analysis (R.S.E.) with a 95.5% confidence level for a thallium type of 10 counts per pixel study exceeded 11%, while it reached acceptable values below 3% for studies with 60 and more counts per pixel. These results indicate that high count rate gated technetium-MIBI myocardial perfusion studies could also be used for reliable left ventricular regional wall motion evaluation.

Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study.

Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combined electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates.

Detection of electrocardiographically imperceptible ventricular pre-excitation by phase imaging.

The sequence of ventricular contraction was studied by radionuclide phase imaging in 25 patients with Wolff-Parkinson-White syndrome. The studies were performed when no signs of precontraction were present in the electrocardiogram; in these cases pre-excitation was either intermittent or suppressable by injection of ajmaline. In 11 of the 16 patients with free wall accessory pathways, precontraction could be detected in spite of electrocardiographically absent pre-excitation. Discrete precontraction was seen also in 2 of the 9 patients with paraseptal accessory pathways. We conclude that antegrade conduction through the accessory pathway does not need to be completely blocked if signs of pre-excitation are absent on the electrocardiogram, and that phase imaging is, at least in some patients (especially those with free wall accessory pathways), a more sensitive technique for detection of pre-excitation (precontraction) than the electrocardiogram.

Obstetrical-neonatal neurological relationship. A replication study.

A study concerning the relationship between neonatal neurological abnormality and 3 parameters of pre- and perinatal condition in a birth cohort of 1507 infants was replicated in a second cohort of 1655 infants. The 3 parameters chosen were preterm birth, intrauterine growth retardation and neonatal acidemia. The neurological examination in the second cohort was carried out by other examiners than in the first cohort. The incidence of neurological abnormality was again found to be raised in all 3 categories and again least in the acidemic subgroup. Also the finding could be confirmed that only in about half of the neurologically abnormal infants could the 3 parameters have exerted any effect at all, which implies the necessity of further analysis. This replication study shows that neurological examination in the newborn period is a reliable tool for the evaluation of the condition of infants with respect to their pre- and perinatal history.