Association of culture medium with growth, weight and cardiovascular development of IVF children at the age of 9 years.

STUDY QUESTION: Is embryo culture media used during an IVF/ICSI treatment associated with differences in growth, body composition and cardiovascular development as determined in 9-year-old singleton IVF children? SUMMARY ANSWER: The choice of in vitro culture medium for human embryos is associated with differences in body weight, BMI, truncal adiposity, waist circumference and waist/hip ratio at the age of 9, while no significant differences were observed in cardiovascular development. WHAT IS KNOWN ALREADY: Children born after IVF/ICSI have an increased risk of low birthweight, which is correlated with a higher risk of cardiovascular diseases. Some studies show that IVF children exhibit a significantly higher systolic and diastolic blood pressure and higher fasting glucose levels compared to naturally conceived children. After alternating assignment to G1™ Version 3 (Vitrolife) or K-SICM (Cook) embryo culture media, birthweight of the resulting children was significantly higher in the Vitrolife group and they remained heavier during the first 2 years of life. STUDY DESIGN, SIZE, DURATION: In this observational cohort study (MEDIUM-KIDS), parents of singletons from a previous study were approached for further follow-up after the ninth birthday of their child. The singletons were born after fresh embryo transfer of cleavage stage embryos resulting from an IVF/ICSI treatment performed between July 2003 and December 2006 in our clinic, when two different culture media were used alternately: either G1™ Version 3 (Vitrolife) or K-SICM (Cook). Follow-up measurements were performed between March 2014 and December 2016. PARTICIPANT/MATERIALS, SETTINGS, METHODS: Parents were invited to attend our clinic with their child for a single visit lasting ~2.5 h. Two experienced clinicians performed all measurements as part of the MEDIUM-KIDS study in a standardized way. Height and weight of the child was measured using calibrated scales, 4-point skinfold thickness measurements were measured in triplicate and waist and hip circumference were measured using a tape measure. The following cardiovascular parameters were measured in a standardized way: blood pressure, heart rate and endothelial function by skin laser-Doppler with iontophoresis using vasodilatory drugs. Cortisol and cortisone concentrations in hair were measured. A blood sample was taken after an overnight fast for insulin, glucose, TSH and lipid analysis. Blood samples of the IVF children were compared with a non-IVF control group. Differences between culture medium groups were analysed by Student's t-test and effects of confounders were analysed using multivariable regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 294 eligible children (168 Vitrolife and 126 Cook), 136 children (75 Vitrolife and 61 Cook) participated in the study. Baseline characteristics of the participating children from the Vitrolife and Cook group were similar. Birthweight was higher in the Vitrolife group, in keeping with the full cohort. After correction for confounders, the difference in weight and BMI attributable to culture medium was 1.58 kg (95% CI: 0.01-3.14) and 0.84 kg/m2 (95% CI: 0.02-1.67), respectively, with the Vitrolife children being heavier. Height and height corrected for age and gender (SDS scores) were similar in both groups. Furthermore, waist circumference was significantly higher in the Vitrolife group with a corrected difference of 3.21 cm (95%CI: 0.60-5.81) leading to a 0.03 increase (95% CI: 0.01-0.05) in waist/hip ratio. Subscapular skinfolds combined with suprailiacal skinfolds (defined as truncal adiposity), was also significantly higher in Vitrolife children (adjusted difference 3.44 cm [95% CI: 0.27-6.62]). Both systolic (adj. beta 0.364 [95% CI: -2.129 to 2.856],) and diastolic (adj. beta 0.275 [95% CI: -2.105 to 2.654]) blood pressures (mmHg) were comparable for the two groups. After an overnight fast, cholesterol, glucose, insulin, low and high-density lipoprotein, triglycerides and TSH were normal and similar in the two groups. Endothelial function in the microcirculation was compared by using maximum perfusion units corrected for the baseline value as a measure for vasodilatory capacity. There were no significant differences between the two groups. Cortisol and cortisone concentration in hair samples were comparable. LIMITATIONS, REASONS FOR CAUTION: A limitation of the original study was its pseudo-randomized design. This and the dwindling enthusiasm of families for participation (47.7% after 9 years) prevent us from drawing robust causal conclusions from the observed association. Nevertheless, to date this is oldest cohort of IVF/ICSI children where culture medium was allocated alternatingly and used in a blinded setting, to be studied. We believe that our participants are representative for the full cohort. The current number of participants was sufficient to rule out differences as little as 3 mmHg in systolic and diastolic blood pressures. WIDER IMPLICATIONS OF THE FINDINGS: This study underlines the importance of structured follow-up of IVF/ICSI children to further elucidate possible long-term health effects. Health professionals and culture medium manufacturers should be aware that small changes in culture conditions and culture medium composition for the early embryo can have long-term health effects. The similar cardiovascular results for the two groups are reassuring but the children may still be too young to detect differences in cardiovascular development. Prolonged follow-up and structured investigations up until adulthood are necessary to gain more insight and reassurance in the cardiovascular development of IVF offspring, although long-term follow-up will become more complicated by confounding life-style and environmental factors possibly influencing development. STUDY FUNDING/COMPETING INTEREST(S): The study was financially supported by the March of Dimes (Grant number #6-FY13-153). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NTR4220.

No effect of IVF culture medium on cognitive development of 9-year-old children.

STUDY QUESTION: Do embryo culture media used during an IVF/ICSI treatment have an effect on cognitive development of singleton IVF children at 9 years of age? SUMMARY ANSWER: Cognitive development of children born after culture in two different embryo culture media is comparable. WHAT IS KNOWN ALREADY: Previously, we have shown that the culture medium used in an IVF/ICSI treatment affects birthweight and weight at 2 years of age after alternating assignment to embryo culture in either K-SCICM (Cook) or G1™ Version 3 (Vitrolife). Children with low birthweight are known to have an increased risk for learning disabilities. Data on cognitive development in general of children born after ART are still conflicting, and the only study reporting on the effects of culture medium on cognitive development shows significant differences in cognitive development between two culture medium groups. STUDY DESIGN SIZE DURATION: In this observational cohort follow-up study (MEDIUM-KIDS), parents of all singletons from our abovementioned study were approached after the ninth birthday of their child to participate in an additional follow-up study. Of the 294 eligible children included in the original study, 119 children (70 Vitrolife and 49 Cook) participated in the current study. PARTICIPANTS/MATERIALS SETTING METHODS: All follow-up measurements were performed between March 2014 and December 2016. CITO (Dutch Central Institute for Test Development) developed the Dutch pupil monitoring system, which involves nationwide independent, standardized, academic achievement score tests to monitor the child's school performance twice a year at fixed time points from third grade onward. The tests include language skills (vocabulary and orthography), mathematics and reading capability and comprehension. Results from the tests performed between third and sixth grades, expressed as ability scores, were obtained from the school. To investigate school performance development over the years, we used a mixed effects multilevel model. The least complex model with the best fit was selected to analyze whether culture medium affects cognitive development in our cohort. The study had enough power to detect a difference in ability score that reflects at least one performance category between the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: No differences were seen in baseline characteristics between participants and non-participants (both parental and children characteristics). For all domains, the random intercept model was used. All analyses showed comparable results for the two culture medium groups. No significant differences were observed for any of the cognitive development domains, even after correction for potential confounders. Parental level of education was higher in the IVF group (45%) if compared to the national average level of education (35%), which most likely explains the higher CITO scores for the IVF children if compared to the National ability scores. LIMITATIONS REASONS FOR CAUTION: A limitation of the study was its pseudo-randomized design and the relatively low participation rate of 40.5%. This and the number of missing data prevent us from drawing robust causal conclusions. However, as this is the first and therewith oldest cohort of children where culture medium was allocated alternatingly and used in a blinded setting, in the same period, with all other conditions identical this study gives up until now the best available evidence. WIDER IMPLICATIONS OF THE FINDINGS: Our study analyzes the effects of culture medium on school performance of children born after IVF/ICSI in a prospective cohort study. Although further research on long-term academic skills and also on behavior is essential, our results are reassuring and should make parents of children born after IVF/ICSI feel comfortable with their children's cognitive development. STUDY FUNDING/COMPETING INTERESTS: The study was financially supported by the March of Dimes (Grant no. #6-FY13-153). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NTR4220.

Routine labour epidural analgesia versus labour analgesia on request: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect on mode of delivery of the routine use of labour epidural analgesia (EA) compared with analgesia on request. DESIGN: Randomised non-inferiority trial. SETTING: One university and one non-university teaching hospital in The Netherlands. POPULATION: Women with a singleton pregnancy in cephalic presentation beyond 36 + 0 weeks' gestation. METHODS: Participants were randomly allocated to receive either routine EA or analgesia on request. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed, with confidence intervals (CI) calculated for the differences in percentages or means. MAIN OUTCOME MEASURES: Rate of operative delivery (instrumental vaginal or caesarean), labour characteristics, and adverse labour and neonatal outcomes. RESULTS: A total of 488 women were randomly allocated to the routine EA (n = 233) or analgesia on request group (n = 255). In the routine EA group, 89.3% (208/233) received EA. According to ITT analysis, 34.8% (81/233) women in the routine EA group had an operative delivery, compared with 26.7% (68/255) in the analgesia on request group (difference 8.1%, 95% CI -0.1 to 16.3). The difference in rate of operative deliveries according to the PP analysis was statistically significant (difference 8.9%, 95% CI 0.4 to 17.4). Inferiority of EA could not be rejected, as in both analyses the upper bound of the confidence interval exceeded the pre-specified inferiority criterion of +10%. Women in the routine EA group had more adverse effects, including hypotension (difference 9.5%, 95% CI 4.2 to 14.9), and motor blockade (difference 6.8%, 95% CI 1.1 to 12.5). CONCLUSION: Non-inferiority of routine EA could not be demonstrated in this trial. Routine EA use is likely to lead to more operative deliveries and more maternal adverse effects. The results of our study do not justify routine use of EA.

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.

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.

Diagnostic accuracy of preoperative tests for lymph node status in endometrial cancer: a systematic review.

BACKGROUND: Approximately 72% of endometrial cancers are FIGO stage I at diagnosis and about 10% have lymph node metastases. An ideal diagnostic test for nodal disease would be able to prevent both overtreatment (i.e. unnecessary lymphadenectomy) and undertreatment (i.e. withholding lymphadenectomy or adjuvant postoperative treatment to patients with lymph node metastases). OBJECTIVES: In this review we compare the accuracy of preoperative tests (computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, CA-125 serum levels, and ultrasonography) for the detection of lymph node metastases in endometrial cancers with the final histopathologic diagnosis after complete pelvic and para-aortic lymphadenectomy as the gold standard. METHOD: A systematic search in MEDLINE (using PubMed), Embase and The Cochrane Library was performed up to 23 July 2012. RESULTS: We found one article that met our inclusion criteria for computed tomography, none for magnetic resonance imaging, 2 for positron emission tomography/computed tomography), 2 for CA-125 and none for ultrasonography. CONCLUSIONS: Due to the lack of high-quality articles on a preoperative test for lymph node status in endometrial cancer, no proper comparison between these modalities can be made.

Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012.

BACKGROUND: Research on noninvasive prenatal testing (NIPT) of fetal trisomy 21 is developing fast. Commercial tests have become available. To provide an up-to-date overview of NIPT of trisomy 21, an evaluation of the methodological quality and outcomes of diagnostic accuracy studies was made. METHODS: We undertook a systematic review of the literature published between 1997 and 2012 after searching PubMed, using MeSH terms 'RNA', 'DNA' and 'Down Syndrome' in combination with 'cell-free fetal (cff) RNA', 'cffDNA', 'trisomy 21' and 'noninvasive prenatal diagnosis' and searching reference lists of reported literature. From 79 abstracts, 16 studies were included as they evaluated the diagnostic accuracy of a molecular technique for NIPT of trisomy 21, and the test sensitivity and specificity were reported. Meta-analysis could not be performed due to the use of six different molecular techniques and different cutoff points. Diagnostic parameters were derived or calculated, and possible bias and applicability were evaluated utilizing the revised tool for Quality Assessment of Diagnostic Accuracy (QUADAS-2). RESULTS: Seven of the included studies were recently published in large cohort studies that examined massively parallel sequencing (MPS), with or without pre-selection of chromosomes, and reported sensitivities between 98.58% [95% confidence interval (CI) 95.9-99.5%] and 100% (95% CI 96-100%) and specificities between 97.95% (95% CI 94.1-99.3%) and 100% (95% CI 99.1-100%). None of these seven large studies had an overall low risk of bias and low concerns regarding applicability. MPS with or without pre-selection of chromosomes exhibits an excellent negative predictive value (100%) in conditions with disease odds from 1:1500 to 1:200. However, positive predictive values were lower, even in high-risk pregnancies (19.7-100%). The other nine cohort studies were too small to give precise estimates (number of trisomy 21 cases: ≤25) and were not included in the discussion. CONCLUSIONS: NIPT of trisomy 21 by MPS with or without pre-selection of chromosomes is promising and likely to replace the prenatal serum screening test that is currently combined with nuchal translucency measurement in the first trimester of pregnancy. Before NIPT can be introduced as a screening test in a social insurance health-care system, more evidence is needed from large prospective diagnostic accuracy studies in first trimester pregnancies. Moreover, we believe further assessment, of whether NIPT can be provided in a cost-effective, timely and equitable manner for every pregnant woman, is required.

Early versus late epidural analgesia and risk of instrumental delivery in nulliparous women: a systematic review.

OBJECTIVE: Review of the literature regarding the relation between the timing of epidural analgesia and the rate of caesarean or instrumental vaginal deliveries. SEARCH STRATEGY: Pubmed, Embase and the Cochrane Library were searched for articles published until 31 July 2010. SELECTION CRITERIA: Studies were selected in which the effects of early latent phase (defined as a cervical dilatation of 3 cm or less) epidural analgesia (including combined-spinal epidural) and late active phase epidural analgesia on the mode of delivery in nulliparous women at 36 weeks of gestation or more were evaluated. DATA COLLECTION AND ANALYSIS: Data extraction was completed by using a data-extraction form. Risk ratio and its 95% confidence intervals were calculated for caesarean delivery and instrumental vaginal delivery. Pooled data were calculated. MAIN RESULTS: The search retrieved 20 relevant articles, of which six fulfilled the selection criteria of inclusion. These six studies reported on 15,399 nulliparous women in spontaneous or induced labour with a request for analgesia. Risk of caesarean delivery (pooled risk ratio 1.02, 95% CI 0.96-1.08) or instrumental vaginal delivery (pooled risk ratio 0.96, 95% CI 0.89-1.05) was not significantly different between groups. AUTHORS' CONCLUSIONS: This systematic review showed no increased risk of caesarean delivery or instrumental vaginal delivery for women receiving early epidural analgesia at cervical dilatation of 3 m or less in comparison with late epidural analgesia.

Value of a single early third trimester fetal biometry for the prediction of birth weight deviations in a low risk population.

OBJECTIVE: To analyze the value of a single ultrasound biometry examination at the onset of the third trimester of pregnancy for the detection of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) at birth in a low risk population. The aim of this study was to develop a simple and useful method for the detection of growth deviations during pregnancy in primary care (midwife or general practitioner) practices. SETTING: A Dutch primary care midwifery practice. STUDY DESIGN: In an earlier study, we developed parity and sex specific fetal growth charts of abdominal circumference (AC) and head circumference (HC) on the basis of ultrasound data of a low-risk midwifery population in the Netherlands. In the present study, we calculated sensitivity, specificity and predictive values at different cut-off points of AC and HC for the prediction of growth deviations at birth. Patients booked for perinatal care between 1 January 1993 and 31 December 2003 (n=3449) were used for the identification of cut-off points (derivation cohort) and those admitted between 1 January 2004 and 31 December 2005 (n=725) were used to evaluate the performance of these cut-offs in an independent population (validation cohort). For the determination of SGA and macrosomia at birth, we used the recently published Dutch birth weight percentiles. RESULTS: Most promising cut-offs were AC or=75(th) percentile for the prediction of macrosomia (birth weight >or=90(th) percentile). Within the validation cohort these cut-offs performed slightly better than in the derivation cohort. For the prediction of SGA, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 53% (95% CI 49-58%), 81% (95% CI 80-83%), 26% (95% CI 23-29%), and 93% (95% CI 93-94%), respectively. The false positive rate was 74%. For the prediction of macrosomia, the values of these parameters were 64% (95% CI 59-69%), 80% (95% CI 78-81%), 23% (95% CI 20-26%), and 96% (95% CI 95-97%), respectively. Here, false positive rate was 77%. No cut-offs were found that predicted extreme birth weight deviations (or=97.7 percentile) sufficiently well. CONCLUSIONS: In a low risk population, we could predict future growth deviations with a higher sensitivity and in a significant earlier stage (at the onset of the third trimester of pregnancy) than with the use of conventional screening methods (i.e., palpation of the uterus only and fundus-symphysis measurement). Sonographic measurement of fetal abdominal circumference enables to detect more than half of cases of SGA at birth and more than two-thirds of cases of macrosomia with acceptable false-positive rates. We suggest that fetuses with biometry results below the 25(th) percentile or above the 75(th) percentile at the onset of the third trimester of pregnancy should be more intensively investigated in order to distinguish between pathology (e.g., IUGR or macrosomia) and physiology and to decide about the appropriate level of further perinatal care.

Hepatitis B virus transmission in The Netherlands: a population-based, hierarchical case-control study in a very low-incidence country.

We report the first population-based case-control study on acute hepatitis B in a very low-incidence country. A case was a Netherlands resident, notified between May 1999 and July 2000 with symptoms and serology compatible with acute hepatitis B. Population controls were randomly selected, with oversampling from men and persons aged 20-39 years. Risk factors were studied using logistical regression, distinguishing confounders and mediators through hierarchical analysis. Participants were 120 cases and 3948 controls. The risk of acute hepatitis B was increased in men who have sex with men, with reporting to have had more than two partners in the past 6 months the only significant risk. In children, adult females and heterosexual males, having parents born in a hepatitis B endemic country was a significant risk. For adult females and heterosexual males, this was largely explained by having a foreign partner. For children this was partly explained by parenteral exposures abroad.

Mothers' views of their childbirth experience two years after term breech delivery.

INTRODUCTION: This study was performed to evaluate mothers' views of their childbirth experience two years after term breech delivery. METHODS: Two years after delivery mothers were asked to fill out a questionnaire concerning their breech birth experience and their view about the care provided to them while giving birth. Outcomes of the planned cesarean section (CS) group were compared with outcomes of the planned vaginal delivery (VD) group, whether or not a vaginal birth was realized or an emergency cesarean section was performed. Any differences were further analyzed by use of logistic regression, controlling for potential confounders. RESULTS: Significantly more women in the planned CS group were reassured about their baby's health (67.4% vs. 37.9%, p=0.0006) at the time of delivery, whereas more women in the planned VD group recalled having been worried about their baby's health at the time of delivery (45.0% vs. 25.6%, p=0.02). Also, more women in the planned VD group experienced more pain during labor and delivery than expected (46.9% vs. 18.5%, p=0.008). In the planned VD group fewer women indicated they had an active say in decision-making (59.1% vs. 85.3%, p=0.001). CONCLUSIONS: Evaluation of the mothers' views of their childbirth experience two years after term breech delivery showed that more women in the planned VD group recalled having been worried about their child's health at the time of delivery, experienced more pain than expected, and reported less involvement in decision-making.

Birth weight and neurodevelopmental outcome of children at 2 years of age after planned vaginal delivery for breech presentation at term.

OBJECTIVE: The purpose of this prospective cohort study was to determine whether planned vaginal delivery for the term singleton baby in breech position increases the risk of abnormal neurodevelopment at 2 years of age and to assess whether the effect is modified by birth weight. STUDY DESIGN: At 2 years of age, all nonrandomized children born in breech position during our participation in the Term Breech Trial were screened for abnormal neurodevelopment with the Ages and Stages Questionnaire. RESULTS: An Ages and Stages Questionnaire at 2 years of age was obtained in 183 of 203 children (90.1%). Twenty-eight percent of these children showed 1 or more abnormal Ages and Stages Questionnaire domains. There were no differences in the risk of having abnormal Ages and Stages Questionnaire domains between planned vaginal delivery and planned cesarean section (P = .99). There was, however, evidence of interaction between mode of delivery and birth weight, with significantly higher risk in neurodevelopmental delay in children with birth weight greater than 3500 g with planned vaginal birth (adjusted odds ratio for interaction term 3.37; 95% confidence interval 1.14 to 9.95). CONCLUSION: Based on the Ages and Stages Questionnaire results at 2 years of age, planned vaginal delivery is associated with an increased risk of neurodevelopmental delay at 2 years of age in term breech children with a birth weight greater than 3500 g.

The importance of imported infections in maintaining hepatitis B in The Netherlands.

In The Netherlands, in May 1999 an enhanced surveillance of hepatitis B was begun to collect detailed information of patients with acute hepatitis B virus (HBV) infection. The objective was to gain insight in transmission routes and source of infection of new HBV cases. Through public health services, patients were interviewed on risk factors. It appeared that the majority (59%) acquired the infection through sexual contact; 52% of these by homosexual and 48% by heterosexual contact. In 60% of the heterosexual cases, the source of infection was a partner originating from a hepatitis B-endemic region. Sexual transmission is the most common route of transmission of acute hepatitis B in The Netherlands and introduction of infections from abroad plays a key role in the current epidemiology of HBV. As well as prevention programmes targeted at sexual high-risk groups, prevention efforts should focus more on the heterosexual transmission from HBV carriers.

Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review.

Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of these differences is needed to decide if genetic testing prior to antidepressant treatment is useful. We conducted a systematic review of the literature on the influence of polymorphisms in the serotonin transporter gene (SERTPR (or 5-HTTLPR) and STin2) on SSRI response. Studies were identified by the use of MEDLINE, EmBase and PsycINFO, references of articles, reviews and information from pharmaceutical companies. Nine studies assessing the influence of SERTPR or STin2 on treatment response were included. Outcome was expressed as the percentage of decrease in depression score (HAM-D or MADRS) or as the percentage of responders (> or =50% reduction on the depression scale). Both study methodologies and study outcomes showed large heterogeneity. Weighted mean decreases in depression score for patients with the s/s, s/l and l/l genotypes were 35.4, 46.3 and 48.0% at week 4, respectively, and 53.9, 54.6 and 48.3% at week 6. Among Caucasian patients, both mean decrease in depression score and response rate were lowest in the s/s group, while among Asian patients, results were inconsistent. Weighted response rates were 36.1% for the 10/12 genotype of the STin2 polymorphism and 80.7% for the 12/12 genotype (chi2=27.8, P<0.001) (only Asians). The available evidence points to a less favourable response to SSRI treatment among Caucasian patients with the SERTPR s/s genotype and among (Asian) patients with the STin2 10/12 genotype. In view of the scarcity and heterogeneity of the studies, however, current information is insufficiently reliable as a basis for implementing genetic testing in the diagnostic work-up of the depressive patient.

Vaccination against hepatitis B in low endemic countries.

A mathematical model that takes transmission by sexual contact and vertical transmission into account was employed to describe the transmission dynamics of hepatitis B virus (HBV) and vaccination against it. The model is an extension of a model by Williams et al. (Epidemiol Infect 1996: 116; 71-89) in that it takes immigration of hepatitis B carriers from countries with higher prevalence into account. Model parameters were estimated from data from The Netherlands where available. The main results were that, given the estimates for the parameters describing sexual behaviour in The Netherlands, the basic reproduction number R0 is smaller than 1 in the heterosexual population. As a consequence, the immigration of carriers into the population largely determines the prevalence of HBV carriage and therefore limits the possible success of universal vaccination. Taking into account the prevalence of hepatitis B carriage among immigrants and an age-dependent probability of becoming a carrier after infection, we estimate that a fraction of between 5 and 10% of carrier states could be prevented by universal vaccination.