Vaginal birth after a caesarean section: the development of a Western European population-based prediction model for deliveries at term.

OBJECTIVE: To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. DESIGN: Registration-based retrospective cohort study. SETTING: Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. POPULATION: A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. METHODS: Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN OUTCOME MEASURES: Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. RESULTS: A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90(th) percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. CONCLUSION: We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries.

Predicting successful intended vaginal delivery after previous caesarean section: external validation of two predictive models in a Dutch nationwide registration-based cohort with a high intended vaginal delivery rate.

OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial).

OBJECTIVE: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy. METHODS: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated. RESULTS: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%. CONCLUSION: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective.

Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, present, and future.

UNLABELLED: We reviewed the English, American, and German literature for articles describing the prevalence, clinical presentation, outcome, therapeutic options, and screening possibilities for fetal/neonatal allo-immune thrombocytopenia (FNAIT), published between January 1950 and March 2007. The reported prevalence of FNAIT in human platelet antigen (HPA)-1a-negative women varies between 1/600 to 1/5000 live births among various populations. The typical picture is that of a neonate presenting with purpura minutes to hours after birth, born to a healthy mother with no history of infection or abnormal bleeding, after an uneventful pregnancy with a normal maternal platelet count. Thrombocytopenia in FNAIT can be severe, with intracranial hemorrhage occurring in 10% to 30% of severe FNAIT cases. Several types of neonatal treatment have been proposed, of which transfusion of HPA-compatible platelets is most effective. Antenatal management of FNAIT consists of weekly maternal intravenous immunoglobulin (IVIG) infusions, with or without oral steroid therapy. Serial fetal platelet transfusions can be provided in cases of failure of IVIG therapy, but the multiple cordocenteses that would be required to administer the platelets entail substantial risk. The possibilities for antenatal screening of first pregnancies are limited. Postnatal screening does not prevent neonatal morbidity and mortality. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the many and varied causes of neonatal thrombocytopenia, explain that fetal/neonatal allo-immune thrombocytopenia (FNAIT) is a rare but devastating cause with potential high risk of recurrence, and recall the treatment options for FNAIT as well as their potential side effects.

Spatial distribution of the dagger nematode Xiphinema index and its associated Grapevine fanleaf virus in French vineyard.

The nematode Xiphinema index is, economically, the major virus vector in viticulture, transmitting specifically the Grapevine fanleaf virus (GFLV), the most severe grapevine virus disease worldwide. Increased knowledge of the spatial distribution of this nematode, both horizontally and vertically, and of correlative GFLV plant infections, is essential to efficiently control the disease. In two infested blocks of the Bordeaux vineyard, vertical distribution data showed that the highest numbers of individuals occurred at 40 to 110 cm depth, corresponding to the two layers where the highest densities of fine roots were observed. Horizontal distribution based on a 10 x 15 m grid sampling procedure revealed a significant aggregative pattern but no significant neighborhood structure of nematode densities. At a finer scale ( approximately 2 x 2 m), nematode sampling performed in a third block confirmed a significant aggregative pattern, with patches of 6 to 8 m diameter, together with a significant neighborhood structure of nematode densities, thus identifying the relevant sampling scale to describe the nematode distribution. Nematode patches correlate significantly with those of GFLV-infected grapevine plants. Finally, nematode and virus spread were shown to extend preferentially parallel to vine rows, probably due to tillage during mechanical weeding.

Repopulation of macrophages in popliteal lymph nodes of mice after liposome-mediated depletion.

Macrophages lining the subcapsular sinus (SCS) and those located in the medulla of popliteal lymph nodes (PLN) of mice were eliminated after subcutaneous (s.c.) injection of dichloromethylene diphosphonate (Cl2MDP)-containing liposomes. No effect of liposome-entrapped Cl2MDP could be seen on nonphagocytic cells, e.g., interdigitating cells (IDC) and B- and T-lymphocytes. One month after injection the eliminated subsets of macrophages were still absent. After 2 mo a small number of macrophages had reappeared along the SCS and in the medulla of the PLN of a few animals. Complete repopulation of the PLN with macrophages was observed only after 5 mo. This extremely long repopulation time could be shortened drastically by local administration of Freund's complete adjuvant (FCA). A small number of macrophages reappeared along the SCS and in the medulla 1 wk after FCA and after 3 wk the repopulation of the PLN with macrophages was complete. Such rapid repopulation of macrophages was not achieved after s.c. injection of paraffin oil or paratyphoid vaccine. These results indicate that the normal rate of influx of mononuclear phagocytes into the PLN is low, but that it can be sped up after administration of FCA.

Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat.

Aggregation of dendritic cells (DCs) in homotypic clusters has been described in vivo in lymph and skin, and here we report studies on homotypic clustering of rat splenic (s) DCs in vitro. Wistar rat sDCs readily formed homotypic clusters in culture, which increased in number and size over time (with a peak at t = 3 h). Keeping the cells at higher densities or treatment with anti-CD43 induced more and larger homotypic clusters. After such enhanced clustering the DCs had increased their T cell stimulating capabilities in syngeneic mixed lymphocyte reaction, and had a higher expression of CD80 and CD86 (signs of maturation). Ag transfer from bovine serum albumin-fluorescein isothiocyanate-pulsed to unpulsed DCs was observed during clustering. Here we also show that sDCs of the biobreeding diabetes-prone (BB-DP) rat, a model of autoimmune diabetes/thyroiditis, formed fewer and smaller clusters than Wistar sDCs, and that DC-DC clustering resulted in only a modest maturation of the cells (as determined in syn MLR and by phenotyping). Anti-CD43 completely restored the clustering defect BB-DP DCs in vitro, yet T cell-stimulating capability was only restored to a limited extent. Ag transfer in BB-DP DC clusters was similar.

Reduced toxoplasmastatic activity of monocytes and monocyte-derived macrophages from AIDS patients is mediated via prostaglandin E2.

OBJECTIVE: To establish the role of prostaglandin E2 (PGE2) formed and released by monocytes and monocyte-derived macrophages (MDM) in the reduced toxoplasmastatic activity of these cells. DESIGN: Determination of PGE2 levels in the serum of AIDS patients, the release of PGE2 by monocytes and MDM from AIDS patients, the toxoplasmastatic activity of these cells and the effect of indomethacin, an inhibitor of PGE2 synthesis, on this cell function. SETTING: Laboratory of Cellular Immunology of the Department of Infectious Diseases, University Hospital, Leiden. PARTICIPANTS: Twenty-six AIDS patients. Healthy blood donors served as controls. RESULTS: The concentration of PGE2 in the serum from AIDS patients was significantly higher compared with serum from controls. Non-stimulated monocytes and lipopolysaccharide-stimulated monocytes and MDM from AIDS patients released significantly more PGE2 than corresponding cells from the controls. The proliferation of Toxoplasma gondii in monocytes and MDM from AIDS patients was significantly higher than in the respective cells from controls. Preincubation of these cells with indomethacin resulted in a decreased proliferation of T. gondii in non-activated monocytes and MDM and in interferon-gamma-activated MDM from AIDS patients. Preincubation of monocytes from healthy donors with PGE2 resulted in a dose-dependent increase of Toxoplasma proliferation which confirms that PGE2 can reduce the toxoplasmastatic activity of monocytes. CONCLUSION: PGE2 is involved in the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients.

Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a role of interleukin-1beta and interleukin-6.

An accumulation of antigen-presenting dendritic cells (DC) in the thyroid gland, followed by thyroid autoimmune reactivity, occurs in normal Wistar rats during iodine deficiency, and spontaneously in diabetic-prone Biobreeding rats. This intrathyroidal DC accumulation coincides with an enhanced growth rate and metabolism of the thyrocytes, suggesting that both phenomena are related. Because DC are known to regulate the hormone synthesis and growth in other endocrine systems (i.e. the pituitary, the ovary, and the testis), we tested the hypothesis that DC, known for their superb accessory cell function in T cell stimulation, act as regulators of thyrocyte proliferation (and hormone secretion). We investigated the effect of (Nycodenz density gradient) purified splenic DC from Wistar rats on the growth rate of and thyroid hormone secretion by Wistar thyroid follicles (collagenase dispersion) in culture. Various numbers of DC and follicles were cocultured during 24 h. The proliferative capacity of thyrocytes was measured by adding tritiated thymidine (3H-TdR) and bromodeoxyuridine, the hormone secretion into the culture fluid was measured by using a conventional T3 RIA. Furthermore, antibodies directed against interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were added to these cocultures to determine the role of these cytokines in a possible DC regulation of thyrocyte growth. Cocultures were also carried out in the presence of antimajor histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated antigen-1alpha (LFA-1alpha) antibodies to possibly interfere with DC-thyrocyte interactions. The addition of DC to thyroid follicles clearly inhibited their 3H-TdR uptake, particularly at a 10:1 ratio, in comparison to follicle cultures alone, both under basal conditions and after TSH stimulation (75 +/- 7% and 49 +/- 11% reduction, respectively, n = 4). The follicle T3 secretion (after TSH stimulation) was also suppressed by DC in this system, but to a lesser extent (at best at an 1:1 ratio, 25 +/- 7% reduction, n = 4). The DC-induced inhibition of thyroid follicle growth was totally abrogated after addition of anti-IL-1beta antibodies; anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated thyrocytes, whereas anti-TNF-alpha demonstrated no effect at all. The antibodies to MHC and to adhesion molecules had also no effect on this DC-induced growth inhibition. The effect of the different anti-cytokine and anti-adhesion antibodies on the T3 secretion from thyroid follicles was not investigated. The clear inhibition of thyrocyte growth by splenic DC (classical antigen-presenting cells) again demonstrates the regulatory role of DC in endocrine systems. Proinflammatory cytokines such as IL-1beta and IL-6 are important mediators in this regulation. The here shown dual role of DC represents a link between the immune and endocrine system, which may form the gateway to the understanding of the initiation of thyroid autoimmune reactions and the thyroid autoimmune phenomena seen in iodine deficiency.

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response.

Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.

Elimination of spleen and of lymph node macrophages and its difference in the effect on the immune response to particulate antigens.

To study the role of macrophages in the in situ immune response to particulate antigens in spleen and popliteal lymph nodes (PLN), mice were injected with dichloromethylene diphosphonate (Cl2MDP)-containing liposomes to eliminate macrophages, followed by immunization with trinitrophenylated sheep red blood cells (TNP-SRBC). Depletion of macrophages in the spleen caused a strong decrease in the number of antibody-forming cells (AFC), which develop after intravenous (i.v.) injection of the antigen. These results strongly suggested the involvement of splenic macrophages in the processing of TNP-SRBC. In particular, the populations of marginal zone macrophages may be involved in the inductive phase of an antibody response to particulate antigens. These macrophages are strategically positioned at the end of the white pulp capillaries in the marginal zone of the spleen and they have their cell processes between the marginal zone-B cells. Elimination of macrophages in PLN had no effect on the number of AFC, which develop after subcutaneous (s.c.) injection of the antigen in the hind footpads. This indicates that the macrophages are not essential for the induction of a local immune response to the particulate antigen TNP-SRBC. After depletion of lymph node macrophages, the number of AFC developing in the spleen after s.c. footpad injection of the antigen increased and the anti-TNP serum titers were elevated. This may well be caused by the fact that more of the antigen reaches the circulation and subsequently stimulates the spleen.

The in situ immune response in popliteal lymph nodes of mice after macrophage depletion. Differential effects of macrophages on thymus-dependent and thymus-independent immune responses.

Mice were subcutaneously (SC) injected in the left hind footpad with dichloromethylene diphosphonate (Cl2MDP)-containing liposomes to eliminate macrophages lining the subcapsular sinus (SCS) and those in the medulla of draining popliteal lymph nodes (PLN). In order to study the effect of depletion of these macrophages on the in situ immune response in the PLN, liposome-treated mice were SC injected in the same footpad with thymus-independent (TI) type 1 antigen trinitrophenylated lipopolysaccharide (TNP-LPS), TI-type 2 antigen TNP-Ficoll or thymus-dependent (TD) antigen TNP-keyhole limpet haemocyanin (TNP-KLH). No major differences were observed in antibody-serum titers of liposome-treated and control animals. After primary as well as secondary immunization with the TD-antigen TNP-KLH, an increase in the number of antibody-forming cells (AFC) was found and the peak of response was delayed in the PLN of liposome-treated animals. Such differences were not observed with the TI-antigens. These results indicate that macrophages lining the SCS and those in the medulla of the PLN are not essential for the induction of an immune response. The positive effect of macrophage-depletion on the number of AFC may be explained by competition for the antigen by macrophages and other antigen-presenting cells.

Development of antibody-forming cells in follicles of lymph nodes of mice after continuous antigenic stimulation.

It was the purpose of the present study to test a hypothesis on the direct differentiation of newly formed memory B cells into antibody-forming cells (AFC) in the follicles of lymph nodes. AFC may develop in follicles when mobile antigen is present at the moment that such memory B cells have completed their differentiation under influence of immune complexes trapped on follicular dendritic cells (FDC). In order to study whether the simultaneous presence of mobile antigen and immobilized immune complexes on FDC alters the normal distribution of AFC in lymph nodes, different immunization protocols with the thymus-dependent antigens trinitrophenylated keyhole limpet haemocyanin (TNP-KLH) and horseradish peroxidase (HRP) were used. Results confirm that, provided that mobile antigen and immobilized immune complexes are present simultaneously, AFC that are normally found in the medulla of the lymph node may also develop in the follicles.

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

INTRODUCTION: Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. PATIENTS AND METHODS: In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. RESULTS: In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy.

Histomorphological aspects of the development of thyroid autoimmune diseases: consequences for our understanding of endocrine ophthalmopathy.

In this short review we will first evaluate the histomorphological aspects of the human and spontaneous animal thyroid autoimmune diseases. These diseases include Hashimoto goiter, primary myxedema, Graves' disease, and the spontaneous forms of thyroiditis in the Bio Breeding (BB) rat, the nonobese diabetic (NOD) mouse, and the obese strain (OS) of chicken. Based on sequential histomorphological events in the animal models of thyroid autoimmune disease, a mechanism for the pathogenesis of thyroid autoimmune disease is proposed. Since one of the human thyroid autoimmune diseases, specifically Graves' disease, is often associated with ophthalmopathy, the histomorphological aspects of the ophthalmopathic process are also evaluated to consider its possible autoimmune character.

Angiotensin sensitivity test revisited.

OBJECTIVE: To determine the validity of a single angiotensin sensitivity test as predictor of pregnancy-induced hypertension with special reference to the dietary sodium intake at the time of testing. METHODS: The angiotensin sensitivity test was successfully performed at 32 weeks' gestation in 104 women. In 90 of these women, the 24-h urinary sodium-creatinine ratio was known. Using an effective pressure dose of 10 ng/kg/min as the cutoff level, test characteristics were assessed in both the total population and after subdivision into a sodium restricted (n = 23) and an unrestricted diet group (n = 67). RESULTS: The incidence of pregnancy-induced hypertension was 13.4%. The number of positive angiotensin sensitivity tests was 7.5%. Test characteristics showed poor sensitivity (22.2%) and high specificity (94.8%); positive and negative predictive values were 40.0% and 88.7%, respectively. None of the sodium-restricted women was angiotensin sensitive. Sodium restriction did not have a significant influence on sensitivity, specificity, and predictive values of the test. CONCLUSION: The angiotensin sensitivity test is not an appropriate screening test to predict hypertensive disorders of pregnancy. No significant effect of dietary sodium restriction was found.

Effect of angiotensin infusion on plasma endothelin in pregnancy.

OBJECTIVE: To study a possible role of plasma endothelin in angiotensin-induced vasoconstriction. STUDY DESIGN: Plasma endothelin levels were measured before and after an angiotensin sensitivity test at 32 gestational weeks in 19 nulliparous women. RESULTS: No significant change in plasma endothelin occurred as a result of angiotensin infusion. CONCLUSION: The angiotensin-induced rise in diastolic blood pressure is not associated with changes in plasma endothelin.

Carnitine deficiency in surgical neonates receiving total parenteral nutrition.

Carnitine plays a key role in the oxidation of fatty acids. Most solutions for parenteral nutrition do not contain carnitine. Because endogenous carnitine synthesis is insufficient in newborns, they are prone to developing a carnitine deficiency when they are dependent on total parenteral nutrition (TPN). Stimulated by the clinical observation of manifest clinical symptoms of carnitine deficiency in one patient, a study of 13 consecutive neonates who received TPN for over 2 weeks was begun. Their plasma carnitine levels before and during carnitine supplementation were determined. All patients had a carnitine intake far below the recommended minimal need of 11 mumol/kg per day. Although only three of them clearly showed clinical symptoms described as carnitine deficiency, carnitine supplementation for all neonates receiving TPN for over 2 weeks is recommended.

[Sodium intake during pregnancy]. / Natriumgebruik tijdens de zwangerschap.

International studies have yielded contradictory results on efficacy of a sodium-restricted diet during pregnancy in preventing and curing hypertension of pregnancy. In the Netherlands three studies have been performed to investigate the value of dietary sodium restriction in pregnancy; they concerned epidemiology, prevention and treatment. Midwives often prescribed this dietary intervention. Urinary sodium excretion was not related to blood pressure changes in pregnancy. Dietary sodium restriction from the third month of pregnancy onwards did not reduce the incidence of pregnancy-induced hypertension. Maternal side effects were a decreased intake of nutrients, decreased maternal weight gain, lowered plasma volume and stimulation of the renin-angiotensin-aldosterone system. A dietary sodium restriction in women with early symptoms of pregnancy-induced hypertension showed no therapeutic effect on blood pressure. There is no place for dietary sodium restriction in the prevention or treatment of hypertension in pregnancy.