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Objective To construct new Dutch reference curves for birthweight by parity, sex and ethnic background. Design Retrospective nationwide study. Material and methods Reference curves for birthweight were constructed using the LMS model and were based on 176,000 singleton births in the Netherlands in the year 2001 (approximately 95% of all births in that year). Results Separate birthweight curves were constructed for male and female babies born from primiparous and multiparous women from 25 to 43 weeks gestational age. The reference curves are similar to the Swedish references. Birthweight at early gestation was lower than in the previous Dutch reference curves and higher from term onwards. Infants of Hindustani women had a significantly lower birthweight, so that a separate reference curve was constructed. Conclusion The new Dutch reference curves show a different pattern than the Dutch reference curves collected more than 50 years ago, reflecting changes in prenatal conditions and care.

Objective. To investigate the feasibility of nationwide perinatal mortality audits in the Netherlands. Study design. Over a one-year period, data for all cases of perinatal mortality were collected. Six perinatal audit panels of professionals within perinatal care investigated and classified causes of death and identified the presence of substandard care factors (SSF). Results. Out of 22,189 newborns, 228 cases of perinatal mortality were audited. Placental pathology, congenital anomalies and preterm birth were the main causes of perinatal death. SSF by caregivers were identified in 72 cases (32%). Almost 20% of the cases were not reported. Conclusions. In the Netherlands, perinatal audit is well supported by all groups of caregivers. It reveals usable facts and findings for the quality assessment of perinatal care. This audit showed that in 9% of the cases perinatal death was related to SSF and potentially avoidable. However, immediate reporting of cases of perinatal death apart from regular registration in the perinatal database proved to be inaccurate. Once a nationwide audit program is realized, in which data from the different caregivers will be collected in a single database instead of collection by linkage afterwards, this problem should be solved. Local audits will start from 2009. These audits will assess mortality cases within their respective areas and may initiate adjustments for perinatal care and optimize the quality of care and inter-professional collaboration. Yearly nationwide audits will focus on specific items (e.g. term or post-term deliveries) and may well offer an opportunity for the development or adjustment of national guidelines.

Contains fulltext : 50221.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. STUDY DESIGN: Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model. RESULTS: The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p

Item does not contain fulltext OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal ablation (Thermachoice trade mark ), regarding efficacy for reducing dysfunctional uterine bleeding and patients satisfaction rate. METHODS: A randomised controlled study was performed in a teaching hospital at the department of gynaecology. One hundred and thirty-seven premenopausal women with dysfunctional uterine bleeding proved by validated menstrual score list were included. Endometrial ablation by a hysteroscopic or non-hysteroscopic method was performed by one gynaecologist. RESULTS: Reduction of menstrual blood loss was significantly more successful at 24 months for thermal ablation with uterine balloon. Success rate measured by menstrual score < 185 for rollerball and thermal balloon ablation are equivalent at 12 and 24 months post-operatively. Satisfaction of the patients for both methods at 24 months post-operatively is not significantly different (respective 75% for rollerball and 80% for uterine balloon). CONCLUSIONS: Endometrial ablation by uterine balloon thermal ablation (Thermachoice trade mark ) is equally effective as hysteroscopic RBE of the endometrium.

OBJECTIVE: To quantify proton containing metabolites by in vitro 1H NMR spectroscopy of amniotic fluids from fetuses with spina bifida and controls. STUDY DESIGN: Fourteen amniotic fluids from spina bifida fetuses and 18 controls were obtained. Concentrations of carbohydrates, organic acids and amino acids were determined. Multiple linear regression analysis was used to evaluate the data. RESULTS: At 15 and 39 weeks amenorrhea, the estimated median amniotic fluid concentrations of succinic acid and glutamine were significantly higher in the spina bifida group compared to controls, 37 and 64%, respectively. Whereas creatine and creatinine were significantly lower, 27 and 36%, respectively. Amenorrhea influenced the concentrations of most compounds with the exception of lactic acid. CONCLUSION: 1H NMR spectroscopy shows significantly higher succinic acid and glutamine concentrations in amniotic fluids derived from spina bifida fetuses compared with controls. A derangement in amino acid metabolism is suggested.

Item does not contain fulltext OBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P

Item does not contain fulltext OBJECTIVE: To examine the association between individual exposures due to occupation, environment and lifestyle on sperm count, we conducted a case-control study among 92 fertile and 73 sub-fertile Caucasian males. STUDY DESIGN: Data from questionnaires were analysed using simple univariate and multivariate logistic regression models. RESULTS: At risk for oligozoospermia are men exposed to pesticides (odds ratio (OR) 8.4; 95% confidence interval (CI) 1.3-52.1), welding (OR 2.8; CI 0.9-8.7), antibiotic use (OR 15.4; CI 1.4-163), a history of mumps (OR 2.9; CI 1.3-6.7), gastrointestinal complaints (OR 6.2; CI 1.4-26.8), decreased intake of fruits (OR 2.3; CI 1.0-5.1), vegetables (OR 1.9; CI 0.7-5.0), or with female fertility disorders in their families (OR 8.4; CI 1.7-41.9). Unlike other studies, no associations were observed between oligozoospermia and exposure to paint or heat. CONCLUSION: This study suggests new risk factors oligozoospermia in man and confirms previously reported results from others.

Item does not contain fulltext OBJECTIVE: To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men. DESIGN: Double-blind, placebo-controlled interventional study. SETTING: Two outpatient fertility clinics and nine midwifery practices in The Netherlands. PARTICIPANT(S): One hundred eight fertile and 103 subfertile men. INTERVENTION(S): Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg. MAIN OUTCOME MEASURE(S): Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men. RESULT(S): Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men. CONCLUSION(S): Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.

Item does not contain fulltext The importance of maternal smoking in the pathogenesis of oral facial clefts is not clear. Susceptibility to cigarette smoke depends on biotransformation of the toxic compounds by mother and embryo. In a population-based case-control study, we investigated the effects of maternal smoking during the first pregnancy trimester and the interaction with polymorphisms in the biotransformation enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase theta 1-1 (GSTT1) on the risk of nonsyndromic oral clefting in the offspring. We recruited 113 infants with nonsyndromic oral clefts and their mothers, as well as 104 control infants and their mothers. Maternal smoking habits were collected regarding the period 3 months before through 3 months after conception. Buccal swabs were taken from mothers and infants for genetic analysis. Maternal smoking was not strongly associated with oral clefting (odds ratio = 1.1; 95% confidence interval = 0.6-2.2), nor were CYP1A1 and GSTT1 polymorphisms. Mothers who smoked and carried the GSTT1-null genotype, however, had an increased risk for having a child with oral clefting compared with nonsmokers with the wild type genotype (odds ratio = 3.2; 95% confidence interval = 0.9-11.6). The risk was almost five times greater (odds ratio = 4.9; 95% confidence interval = 0.7-36.9) in mothers and infants both having the GSTT1-null genotype compared with both having the wild genotype. There was no interaction between CYP1A1 and maternal smoking in relation to oral clefting.

Evidence of the impact of maternal nutritional status on pregnancy outcome is increasing. However, reference values for vitamin and homocysteine concentrations in maternal blood during normal pregnancy are scarce, and are lacking for the preconceptional period and early pregnancy. Thus, in a longitudinal study we evaluated vitamin and homocysteine concentrations in 102 nulliparous women with an uneventful singleton pregnancy and normal outcome not using supplements. The physiological changes in vitamin and homocysteine concentrations in blood were determined from the preconceptional period throughout pregnancy until 6 weeks post-partum. The vitamins evaluated comprised retinol, thiamin, riboflavin, pyridoxal 5′-phosphate, folate in serum and erythrocytes, vitamin B12and α-tocopherol. The plasma homocysteine concentration was also measured, considering the essential roles of folate, vitamin B6and vitamin B12in homocysteine metabolism. The concentrations of retinol, thiamin, pyridoxal 5′-phosphate serum folate and vitamin B12decreased during pregnancy. In contrast, the concentrations of riboflavin, α-tocopherol, and folate in erythrocytes increased or showed only minor changes. Homocysteine concentrations also remained approximately constant during pregnancy. These observations emphasize the importance of preconceptional and post-partum concentrations of vitamins in the evaluation of pregnancy-induced changes. These data have provided valuable reference values for vitamins and homocysteine before, during and after pregnancy in order to contribute to better diagnosis of maternal deficiencies and to study further the relationship between maternal vitamin status and adverse course and outcome of pregnancy.

Objective: To evaluate the impact of cigarette smoking on male factor subfertility and the semen parameters of sperm count, motility, and morphology by questionnaire and determination of the cotinine concentrations in blood and seminal plasma of fertile and subfertile males. Design: Case-control study of 107 fertile and 103 subfertile males who provided a standardized blood and semen specimen and completed a self-administered questionnaire about their smoking habits. Setting: Outpatient fertility clinic of the University Medical Centre St. Radboud, Nijmegen, The Netherlands. Patient(s): One hundred seven fertile and 103 subfertile males. Intervention(s): Vena puncture and semen collection. Main Outcome Measure(s): Blood and seminal plasma cotinine levels in relation to semen parameters. Result(s): A higher frequency of cigarette smoking was observed in subfertile males than in fertile males, with an odds ratio of 1.7 (95% confidence interval, 0.9–3.2). The self-reported number of cigarettes smoked per day correlated with the cotinine concentrations in blood and seminal plasma for both groups. A small but statistically significant correlation was found between cotinine concentrations in seminal plasma and the percentage of abnormal sperm morphology, but not for other semen parameters ( r s = 0.19). Conclusion(s): Although the mechanism of the toxicity of cotinine on sperm morphology is not clear, this study indicates only a minor effect of cigarette smoking on male factor subfertility, which is probably due to compounds in cigarette smoke other than nicotine (cotinine).

Objective: To investigate a possible involvement of glutathione S-transferases, major detoxificating enzymes, in the pathophysiology of preeclampsia. Methods: Levels of glutathione S-transferase isoforms and enzyme activity were assessed in placental and decidual tissues in 22 preeclamptic and 21 normotensive women. Measured values were analyzed statistically using the Mann-Whitney U test for comparison between groups, and the signed-rank test for comparison within groups. Results: Glutathione S-transferase pi is the main glutathione S-transferase isoform in normal placental and decidual tissue. Lower median placental and decidual glutathione S-transferase pi levels were found in preeclamptic women compared with controls: 1268 (range: 524–3925) and 2185 (range: 503–6578), P = .05, for placenta; 1543 (range: 681–2967) and 2169 (range: 893–3929), P = .02, for decidua. The total amount of glutathione S-transferases in control and preeclamptic pregnancies was higher in decidua than in placenta. Conclusion: Reduced levels of glutathione S-transferase class pi in preeclampsia might indicate a decreased capacity of the glutathione/glutathione S-transferase detoxification system. A higher total amount of glutathione S-transferases in decidual tissue might point to a more pronounced protective role of decidua compared with placenta.

We studied plasma GSTA1-1 concentrations in preconceptionally recruited epileptic women who received antiepileptic drugs (n = 99) and a control group of healthy women (n = 106). Mean plasma GSTA1-1 concentrations in the control group did not show significant changes preconceptionally and throughout pregnancy. Six weeks postpartum, however, a significant increase in the mean plasma GSTA1-1 concentration (p < 0.001) was found as compared to preconceptional levels and levels during pregnancy. The mean plasma GSTA1-1 concentration in epileptic women was significantly higher in the 4th gestational week compared to those determined in healthy pregnant women (1.68 versus 1.08 μg/l, p < 0.001). Values between the groups in the second and third trimester and postpartum period showed no significant differences.

Objectives: To compare efficacy, acceptability and patient preference of a single oral dose of fluconazole with a single intravaginal dose of 500 mg clotrimazole (medication groups) in women with vaginal candidosis visiting gynaecologists or general practitioners (study groups). Design : A comparative, randomized multicenter study. Events: Baseline visit and treatment, short-term follow-up after 1 week and long-term follow-up after 4 weeks. At each visit, symptoms were graded and cultures were obtained. Results: Symptomatic and mycological efficacy did not differ statistical significant in the medication groups or study groups. A complicated history regarding vaginal candidosis was more often found among gynaecologists, yielding poorer results of treatment. Patients preferred oral treatment over intra-vaginal treatment. Conclusions: No differences were found in the clinical and mycological efficacy of both drugs. Clinical results were related to parameters originating from the patients history, resulting in less favourable results in the study group of gynaecologists.

Contains fulltext : 48401.pdf (Publisher’s version ) (Closed access) Cytomegalovirus (CMV) is one of the most common causes of congenital infection without an effective treatment or an effective vaccine available to date. The emphasis has to be on preventive strategies, which rely on the epidemiological situation. The incidence of congenital CMV infections, however, is not known for The Netherlands. Therefore, a prospective virological study was carried out in a population of 7,524 pregnant women and 7,793 newborns. CMV-specific IgG antibodies were determined in cord blood by ELISA. When CMV antibodies were present, a CMV specific PCR was performed on the throat swab. A positive PCR was confirmed by urine culture. In addition, the seroepidemiology for CMV was investigated in the metropolitan region (Amsterdam and Rotterdam) which has a different ethnic composition. Congenital CMV infection was found in 7 infants (0.9 per 1,000). None had symptoms at birth or during 24 month follow-up. Carriage or CMV was 41%, with a variation between 35% and 100% depending on ethnicity. The ethnic composition in the south-eastern region was different from that in large cities, but similar to that in the rest of the country. The incidence of congenital CMV infections in The Netherlands is the lowest described to date, which does not justify special preventive policies.

Numerous disorders, including adult respiratory distress syndrome and AIDS, are associated with a deficiency of glutathione, an intracellular antioxidant. Because N-acetylcysteine is a precursor of glutathione as well as a direct radical scavenger, and because preeclampsia is associated with decreased levels of several antioxidants, a randomized, double-blind, placebo-controlled trial of orally administered N-acetylcysteine was undertaken in women with severe, early-onset preeclampsia and/or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Severe preeclampsia was defined as a diastolic blood pressure of 110 mm Hg or higher with proteinuria of at least 0.3 g/L. Half of the 38 women admitted to the study received 3 effervescent tablets containing 600 mg N-acetylcysteine every 8 hours, whereas the others received placebo tablets. The median interval from treatment to delivery was 6 days in the women given N-acetylcysteine and 5 days in placebo recipients, not a significant difference. The treatment group had stable maternal plasma N-acetylcysteine levels of 20 μmol/L. Whole blood and plasma levels of glutathione and other thiols were unaffected in actively treated women except for lower plasma homocysteine levels. Gestational age at delivery did not differ significantly between the 2 groups. A majority of women in both groups underwent operative delivery because of the mother's worsening condition or fetal distress. Women in the 2 groups had comparable numbers of complications. Approximately one third of those in each group reported side effects. Rates of neonatal morbidity and mortality did not differ in the 2 groups. The investigators conclude that oral treatment with N-acetylcysteine does not improve either maternal or neonatal outcomes in cases of severe preeclampsia and/or HELLP syndrome. It remains possible, however, that earlier treatment might confer benefit.

Contains fulltext : 59251.pdf (Publisher’s version ) (Closed access) BACKGROUND: Inadequate maternal vitamin intake during pregnancy has been suggested as a risk factor for cleft lip with or without cleft palate (CLP). The independent role of folate has not been clarified. METHODS: To investigate the association between maternal folate intake by supplement and food and the risk of CLP offspring, a case-control study was conducted in the Netherlands (1998-2000) among 174 mothers of a child with nonsyndromic CLP and 203 mothers of a child without congenital malformations. RESULTS: Daily use of a folic acid supplement by mothers starting from 4 weeks before until 8 weeks after conception gave a 47% CLP risk reduction compared to mothers who did not use these supplements [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33, 0.85]. Ninety-three percent of the users took a supplement containing folic acid only. Dietary folate intake reduced CLP risk independently in a dose-response manner. The largest risk reductions were found on those mothers who had a diet of more than 200 microg folate per day in combination with a folic acid supplement (OR: 0.26, 95% CI: 0.09, 0.72). CONCLUSIONS: We demonstrated that periconceptional maternal folic acid supplement use was beneficial to reduce the risk for CLP. An additional effect of food folate was shown.

Item does not contain fulltext OBJECTIVE: This study was undertaken to investigate the involvement of maternal and infant B vitamins and homocysteine as risk factors for orofacial clefting. STUDY DESIGN: Venous blood samples were taken from 96 infants with nonsyndromic orofacial clefts and 88 infants without a congenital malformation and from their mothers at approximately 14 months after the index pregnancy. Red blood cell and serum folate, serum vitamin B(12), whole blood vitamin B(6) as pyridoxal-5'-phosphate (PLP), and plasma homocysteine concentrations were measured. RESULTS: A vitamin B(12) concentration of 185 pmol/L or less and a PLP concentration of 44 nmol/L or less in mothers increased the risk of having a child with an orofacial cleft (odds ratio [OR]=3.1; 95% CI: 1.3-7.4, OR=2.9; 95% CI: 1.2-7.1, respectively). Infants with orofacial clefts had a 15% lower serum folate concentration compared with controls (P=.06). CONCLUSION: A low vitamin B(12) and PLP concentration in mothers increased the risk of orofacial clefts in the offspring. A possible role of the infant's folate status is suggested.

Background: Myo-inositol plays a key role in an important intracellular signalling pathway. A deranged myo-inositol metabolism has been associated with neural tube defects. A myo-inositol loading test was performed to investigate the kinetics in healthy women of reproductive age. Methods: Five healthy non-obese females {mean age (standard deviation: SD) 22·8 (2·2) years} were recruited at the University Medical Center Nijmegen. Blood samples were drawn fasting and at 20, 40, 60, 90, 180 and 270 min after ingestion of 100 mg/kg body weight of myo-inositol. Urine samples were collected before myo-inositol loading and at 180 and 270 min post-loading. Samples were analysed for serum myo-, epi- and scyllo-inositol and glucose concentrations by gas chromatography. Plasma insulin concentrations were determined by radio-immunoassay. Random intercept models were fitted to evaluate the data. Results: The estimated myo-inositol and scyllo-inositol concentrations both reached maximum values at 180 min post-loading, respectively: mean (SD) 101·5 (9·2) µmol/L and 1·09 (0·11) µmol/L. The estimated plasma insulin and serum glucose concentrations decreased slightly but significantly during the experiment: P < 0·0001 and P < 0·05, respectively. At 180 and 270 min post-loading, urinary myo-inositol concentrations were increased and urinary glucose concentrations were unchanged. Conclusions: Myo-inositol enters the bloodstream quickly after oral ingestion and a small amount of myo-inositol is converted to scyllo-inositol. The synthesis of glucose from myo-inositol could not be detected by serum measurements. These data can be used in further research into the association between myo-inositol and neural tube defects.

To investigate the impact of calcium, magnesium, zinc, and copper in blood and seminal plasma on semen parameters, 107 fertile and 103 subfertile males provided a standardized blood and semen specimen. Total calcium and magnesium concentrations were determined with colorimetric end point assay procedures. Zinc and copper were determined by flame atomic absorption spectrophotometer (AAS). Semen analysis was performed according to World Health Organization guidelines (1992). The concentrations of calcium, magnesium, zinc, and copper in blood and seminal plasma were not different between the subfertile and fertile group. Weak correlations were demonstrated between blood plasma zinc concentrations and sperm count (rs = 0.18), sperm motility (rs = 0.15), and abnormal sperm morphology (rs = 0.13). Zinc and magnesium concentrations in seminal plasma correlated weakly with sperm count (rs = 0.17 and rs = 0.16, respectively), and copper concentrations in blood plasma with motility (rs = 0.25). Strong correlations were found between calcium, magnesium, and zinc in seminal plasma. Although calcium, magnesium, zinc, and copper play an essential role in spermatogenesis and fertility, the determination of these elements in blood and seminal plasma does not discriminate on the basis of fertility in this group of men.

Item does not contain fulltext OBJECTIVE: To determine whether severe pre-eclampsia complicated by hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome alters neutrophil oxygen radical production. MATERIALS AND METHODS: Neutrophils were obtained from 10 healthy non-pregnant, 9 normal pregnant and 9 women with severe pre-eclampsia with concurrently HELLP syndrome. Oxygen radical production was evaluated using luminol-enhanced chemiluminescence and measured by cytochrome C reduction. Furthermore we incubated sera from cases and controls with isolated healthy neutrophils and measured their capacity to generate oxygen radicals. RESULTS: Unstimulated neutrophil oxygen radical production was significantly lower in severe pre-eclamptics compared with healthy non-pregnant and pregnant subjects, whereas phorbol ester-induced oxygen radical production did not differ among categories. Cytochrome C reduction of unstimulated neutrophils showed similar results. Healthy neutrophils incubated with sera from pre-eclamptics enhanced the oxygen radical production significantly more than neutrophils incubated with sera from the healthy subjects. CONCLUSIONS: Severe pre-eclampsia is characterised by decreased unstimulated neutrophil oxygen radical production. This may be the result of an exhausted cellular response due to stimulation by a factor present in the serum of these patients.

In this study, the semen analysis results of a fertile population were compared with those from a subfertile population, in order to establish normal cut-off values for the standard semen parameters with the aid of receiver operating characteristic (ROC) curve analysis. The fertile group comprised healthy males (n = 107) without any history of fertility problems, the partners of whom had had a spontaneous pregnancy within one year of unprotected intercourse and were pregnant at the time of the male's inclusion into the study. A total of 103 males from couples attending the infertility clinic, and with an initial sperm count of

Objective: To compare the efficacy and patient acceptability of intranasal versus transdermal 17β-estradiol (E2) delivery systems for postmenopausal symptoms. Methods: Postmenopausal women were randomly assigned to intranasal 17β-E2, 300 μg daily (n = 176) or transdermal 17β-E2 (delivering 50 μg/day), two patches per week (n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. Results: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups (P < .001). The difference between groups in the Kupperman Index score of −0.5 ± 0.9 (95% confidence interval −2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P = .02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy (P < .001). Satisfaction was greater with intranasal therapy at week 16 (P < .001). Conclusion: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients’ choice for long-term treatment.

Pre-eclampsia is a major complication of pregnancy with high morbidity and mortality rates. The aetiology is still unclear but impaired detoxification or enhanced levels of reactive (oxygen) metabolites may contribute to the development or maintenance of pre-eclampsia. Glutathione and glutathione-related enzymes, as one of the major detoxificating and free-radical scavenging systems, may play a role in controlling the disease. Seventeen normotensive pregnant women and 24 pre-eclamptic women were investigated prospectively with respect to placental and decidual levels of total glutathione (GSH), glutathione S-transferase activity (GST), selenium-dependent glutathione peroxidase (SeGPX) and total glutathione peroxidase activity (TGPX, both selenium- and non-selenium-dependent GPX). Decidual levels of glutathione and related enzymes were compared with placental levels, and the investigated parameters in pre-eclampsia were compared with those in normotensive pregnancy by the Mann–Whitney U -test. Clinical data were correlated with biochemical parameters by Spearman's correlation test. Glutathione levels were significantly higher in decidua as compared with placenta. Glutathione levels were elevated in pre-eclampsia and HELLP (haemolysis, elevated liver enzymes, low platelets) as compared to normotensive pregnancy for decidua and in the placenta of patients with pre-eclampsia only. Glutathione S-transferase activity was not different between the two groups. In the placenta of patients with pre-eclampsia+HELLP, total glutathione peroxidase activity was elevated versus controls. Selenium-dependent glutathione peroxidase activity was higher in decidua versus placenta and in decidua of pre-eclamptic versus control subjects. Enhanced glutathione concentrations and glutathione peroxidase activities were often found in placenta and decidua in pre-eclampsia, probably as a compensatory mechanism to prevent further damage by peroxides, (oxygen) radicals or other toxins in the placenta or in the feto–placental interface.

To investigate the value of plasma glutathione S-transferase Pi1-1(GSTP1-1) measurements in the assessment of hemolysis in hypertensive disorders of pregnancy.Plasma GSTP1-1 and haptoglobin levels and serum lactate dehydrogenase (LDH) activity were measured in 81 healthy nonpregnant female blood donors between 20 and 40 years of age, 41 women during uncomplicated normotensive pregnancy, 35 women with pregnancy-induced hypertension, 67 women with preeclampsia, and 34 women with the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Levels in hypertensive pregnancies were compared to levels in normotensive pregnancy, and levels in normotensive pregnancy were compared to levels in blood donors by the Mann-Whitney U-test.Median GSTP1-1 and LDH levels were significantly increased (p0.01) and haptoglobin significantly decreased (p0.01) in preeclampsia and the HELLP syndrome as compared to normotensive pregnancy. Both GSTP1-1 and LDH levels were significantly higher in normotensive pregnant women as compared to nonpregnant women (p0.0001). The percentage of preeclamptic patients (26.9%) or patients with the HELLP syndrome (73.5%) with elevated GSTP1-1 levels was lower than those with elevated LDH (38.8% and 100%, respectively) or decreased haptoglobin levels (41.8% and 97%, respectively).We conclude that plasma GSTP1-1 levels may provide useful information on hemolysis in hypertensive disorders of pregnancy in addition to serum LDH activity and plasma haptoglobin levels and that the degree of hemolysis in hypertensive disorders of pregnancy, especially in the HELLP syndrome, is probably less prominent than generally assumed.

Serum levels of aminotransferases, lactate dehydrogenase, gammaglutamyl transferase, alkaline phosphatase, albumin and conjugated bilirubin, measured in 54 women at a median of 31 months (range 3-101) after pregnancies complicated by the HELLP syndrome, were not elevated. Total bilirubin levels, however, were elevated in 20% of these women; this represents a significant difference from the prevalence in 151 women with a previous normal pregnancy (X 2 = 12.23, P < 0.001), or in the normal female population (X 2 = 22.34, P < 0.00001). This raises the possibility that a dysfunction of the bilirubin-conjugating mechanism represents a risk factor for the development of the HELLP syndrome.

To investigate possible delivery-related impaired neonatal hepatocellular integrity by assessment of arterial and venous umbilical cord plasma levels of glutathione S-transferase Alpha 1-1.Glutathione S-transferase Alpha 1-1 levels were assessed in arterial and venous umbilical cord, and maternal venous plasma samples. The influence of maternal, delivery, and neonatal characteristics on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels was studied, using linear regression analysis after log-transformation.Median (range) arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels were higher than venous umbilical cord levels (9.68 [0.64-1125] microg/L and 7.66 [0.78-987.5] microg/L, respectively, P.005). Median (range) arterial and venous umbilical cord glutathione S-transferase Alpha 1-1 levels were higher than, and did not correlate with, maternal venous plasma levels (8.79 [1.79-183] microg/L and 6.47 [1.58-164.5] microg/L versus 1.47 [0.46-10.4] microg/L, P.001). Neonates born vaginally demonstrated higher median (range) levels than those delivered by cesarean (13.41 [1.02-1125] microg/L and 5.73 [0.64-172.90] microg/L, respectively, P.001). Neonates with unfavorable pH (arterial pH under 7.20) demonstrated higher median (range) levels than those with normal pH (arterial pH at least 7.20) (15.15 [0.77-1125] microg/L and 8.82 [0.64-120.90] microg/L, respectively, P.001). Stepwise multiple linear regression analysis showed that birth weight had the largest influence on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels, followed by arterial base deficit, and route of delivery.Arterial umbilical cord glutathione S-transferase Alpha 1-1 plasma levels, being unrelated to maternal venous levels, might give a reliable impression of early neonatal hepatocellular integrity and may become an additional indicator of neonatal condition immediately after birth.

We studied pregnancy outcome in preconceptionally recruited epileptic and control women in a multi-centre prospective non-intervention study at two university hospitals and three general hospitals. We evaluated 225 singleton pregnancies: 119 pregnancies of epileptic women who received either antiepileptic drugs (AEDs) ( n = 99) or not ( n = 20), and 106 pregnancies of controls. The main outcome measures were abnormal pregnancy outcome: major and minor congenital malformations, ectopic pregnancies, abortions; neonatal headcircumference; birth weight and birth length. Epileptic women had a two-fold risk of having an abnormal pregnancy outcome or an infant with minor malformations compared to healthy controls (odds ratio, with 95% confidence interval, respectively 2.1 (1.1, 4.0) and 2.0 (1.0, 4.0)). A significant correlation between the prevalence of abnormal pregnancy outcome and duration of epilepsy and AED treatment was found (risk increased by 9% (6%, 16%) per annum). No significant effect in terms of the type, the number or the serum level of the AEDs could be established. The head circumference of infants of epileptic mothers was significantly smaller (0.7 (1.2, 0.28 cm) compared to controls. An effect on the outcome of pregnancy of maternal folate supplementation or of folate blood concentrations during the periconceptional period and first trimester of pregnancy could not be determined. The severity of maternal epilepsy and/or AED treatment influences pregnancy outcome.

This report examines a patient with recurrent attacks of thrombo-embolism due to a protein C deficiency. Alterations in the coagulation during pregnancy and the possible consequences of an altered coagulation during pregnancy will be discussed.

To compare efficacy, safety and patient preference of a single oral dose of 150 mg fluconazole with a single intravaginal dose of 1200 mg miconazole in vaginal candidosis. To investigate the effect of treatment on Candida colonization of throat and rectum.Double-blind, double-dummy, parallel, randomized trial. Ninety-nine patients with symptomatic and mycologically verified candidosis were given 150 mg fluconazole with an intravaginal dummy, or 1200 mg miconazole with an oral dummy. Patients with an inadequate short-term response were given a second dose.At each visit a patient self assessment and an investigators' global assessment were recorded, and cultures were set up. Adverse events were recorded and laboratory tests were performed. Clinical cure or improvement (investigators' assessment) was obtained in 100% (short-term) and 95% (long term) of the fluconazole group and in 94% and 90%, respectively, of the miconazole group. Patients considered the treatment excellent or good in 81% (short-term) and 88% (long-term) in the fluconazole group and in 84% and 76%, respectively, of the miconazole group. Mycological cure was achieved in 98% (short-term) and 73% (long-term) of the fluconazole group and in 96% and 82% respectively in the miconazole group. The differences in results were not significant. Both treatments significantly reduced the number of positive rectal cultures: neither treatment had a significant effect on throat cultures. Four percent of the patients preferred intravaginal therapy.A single dose fluconazole is as safe and effective as a single dose of miconazole.

A new detection reagent for the determination of the lecithin-sphingomyelin ratio in amniotic fluid using precoated thin-layer plates containing an organic binder is described.

Objective. To explore the feasibility of a national perinatal audit organization. Design. Validation study. Setting. Three regions in the Netherlands. Population. 228 cases of perinatal mortality. Methods. Narratives of perinatal mortality cases were assessed by a panel of representatives of all perinatal care provider groups. 123 cases were assessed twice. Consensus was defined as 75% agreement. For the chance corrected agreement Cohen's kappa statistic was used. Main outcome measures. Consensus and the chance corrected agreement on three cause of death classifications. The presence or absence of substandard factors (SSF) with the care provider, the organization of care and the relation of the SSF with perinatal death. Results. Consensus rates and chance corrected agreement for three cause of death classifications ranged from 92 to 96% and kappa 0.87 to kappa 0.93 (very good agreement), with comparable confidence intervals and similar values in the validation subset of 123 cases. On the presence of SSF at the level of the care provider consensus and chance corrected agreement was 68% and kappa 0.53 (moderate), with comparable values in the subset of 123 cases. Consensus for the relation between SSF at the level of the care provider and perinatal death was 81.4% and kappa 0.68 (good). Conclusion. Perinatal audit on a national level with relatively large audit groups with many different care providers is feasible.