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Objective: Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial At Term) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates. We report the maternal health-related quality of life (HR-QoL) that was measured alongside the trial at several points in time.Methods: Both randomized and non-randomized women were asked to participate in the HR-QoL study. Women were asked to fill out written validated questionnaires, covering background characteristics, condition-specific issues and the Short Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression scale (HADS), and Symptom Check List (SCL-90) at baseline, 6 weeks postpartum and 6 months postpartum. We compared the difference scores of all summary measures between the two management strategies by ANOVA. A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical (PCS) and mental (MCS) components of the SF-36. Analysis was by intention to treat.Results: We analyzed data of 361 randomized and 198 non-randomized patients. There were no clinically relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures; e.g., on the SF-36 (PCS: P = .09; MCS: P = .48). The PCS and the MCS were below norm values at inclusion. The PCS improved over time but stayed below norm values at 6 months, while the MCS did not improve.Conclusion: In pregnancies complicated by IUGR beyond 36 weeks, induction of labor does not affect the long-term maternal quality of life. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between hyperemesis gravidarum (HG) severity and early enteral tube feeding on cardiometabolic markers in offspring cord blood. We included women admitted for HG, who participated in the MOTHER randomised controlled trial (RCT) and observational cohort. The MOTHER RCT showed that early enteral tube feeding in addition to standard care did not affect symptoms/birth outcomes. Among RCT and cohort participants, we assessed how HG severity affected lipid, c-peptide, glucose and free thyroxine cord blood levels. HG severity measures were severity of vomiting at inclusion and 3 weeks after inclusion, pregnancy weight gain and 24-h energy intake at inclusion, readmissions and duration of hospital admissions. Cord blood measures were also compared between RCT participants allocated to enteral tube feeding and those receiving standard care. Between 2013-2016, 215 women were included: 115 RCT and 100 cohort participants. Eighty-one cord blood samples were available. Univariable not multivariable regression analysis showed that lower maternal weight gain was associated with higher cord blood glucose levels ( β : -0·08, 95% CI -0·16, -0·00). Lower maternal weight gain was associated with higher Apo-B cord blood levels in multivariable regression analysis ( β : -0·01, 95% CI -0·02, -0·01). No associations were found between other HG severity measures or allocation to enteral tube feeding and cord blood cardiometabolic markers. In conclusion, while lower maternal weight gain was associated with higher Apo-B cord blood levels, no other HG severity measures were linked with cord blood cardiometabolic markers, nor were these markers affected by enteral tube feeding.

Objective: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity., Material and Methods: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester., Results: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively., Conclusion: Depression, anxiety, and PTSD symptoms are common years after HG occurred.

Introduction: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies., Material and Methods: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies., Results: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03)., Conclusions: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG., Material and Methods: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4., Results: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03)., Conclusions: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity., Study Design: We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point RESULTS: 215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48)., Conclusions: There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG., Competing Interests: Declaration of Competing Interest None declared. Completed disclosure of interests form available to view online as supporting information., (Copyright © 2020. Published by Elsevier B.V.)

Objective: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity., Study Design: For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures., Results: We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (β) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures., Conclusion: Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity., Competing Interests: Declaration of Competing Interest None declared. Completed disclosure of interests form available to view online as supporting information., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Hyperemesis gravidarum (HG) leads to dehydration, poor nutritional intake, and weight loss. HG has been associated with adverse pregnancy outcomes such as low birth weight. Information about the potential effectiveness of treatments for HG is limited. Objective: We hypothesized that in women with HG, early enteral tube feeding in addition to standard care improves birth weight. Design: We performed a multicenter, open-label randomized controlled trial [Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER)] in 19 hospitals in the Netherlands. A total of 116 women hospitalized for HG between 5 and 20 wk of gestation were randomly allocated to enteral tube feeding for ≥7 d in addition to standard care with intravenous rehydration and antiemetic treatment or to standard care alone. Women were encouraged to continue tube feeding at home. On the basis of our power calculation, a sample size of 120 women was anticipated. Analyses were performed according to the intention-to-treat principle. Results: Between October 2014 and March 2016 we randomly allocated 59 women to enteral tube feeding and 57 women to standard care. The mean ± SD birth weight was 3160 ± 770 g in the enteral tube feeding group compared with 3200 ± 680 g in the standard care group (mean difference: -40 g, 95% CI: -230, 310 g). Secondary outcomes, including maternal weight gain, duration of hospital stay, readmission rate, nausea and vomiting symptoms, decrease in quality of life, psychological distress, prematurity, and small-for-gestational-age, also were comparable. Of the women allocated to enteral tube feeding, 28 (47%) were treated according to protocol. Enteral tube feeding was discontinued within 7 d of placement in the remaining women, primarily because of its adverse effects (34%). Conclusions: In women with HG, early enteral tube feeding does not improve birth weight or secondary outcomes. Many women discontinued tube feeding because of discomfort, suggesting that it is poorly tolerated as an early routine treatment of HG. This trial was registered at www.trialregister.nl as NTR4197., (© 2017 American Society for Nutrition.)

Introduction: If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk., Material and Methods: We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities., Results: We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p = 0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p < 0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively)., Conclusion: In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective  We assessed experience and preferences among term women undergoing induction of labor with oral misoprostol or Foley catheter. Study Design  In 18 of the 29 participating hospitals in the PROBAAT-II trial, women were asked to complete a questionnaire within 24 hours after delivery. We adapted a validated questionnaire about expectancy and experience of labor and asked women whether they would prefer the same method again in a future pregnancy. Results  The questionnaire was completed by 502 (72%) of 695 eligible women; 273 (54%) had been randomly allocated to oral misoprostol and 229 (46%) to Foley catheter. Experience of the duration of labor, pain during labor, general satisfaction with labor, and feelings of control and fear related to their expectation were comparable between both the groups. In the oral misoprostol group, 6% of the women would prefer the other method if induction is necessary in future pregnancy, versus 12% in the Foley catheter group (risk ratio: 0.70; 95% confidence interval: 0.55-0.90; p =  0.02). Conclusion  Women's experiences of labor after induction with oral misoprostol or Foley catheter are comparable. However, women in the Foley catheter group prefer more often to choose a different method for future inductions., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone., Methods: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 μg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466., Findings: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86-1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69-1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure., Interpretation: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness., Funding: FondsNutsOhra., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: In a recent randomized controlled trial we found that induction of labor in women with gestational hypertension (GH) or mild (preeclampsia) PE at term prevented high risk situations without increasing the cesarean section (CS) rate. We aimed to assess the predictability of the risk of CS., Study Design: We used multivariable logistic regression analysis to identify predictive factors. Two models were created, one including antepartum and one including antepartum and intrapartum variables. The predictive capacity was assessed with ROC analysis and calibration., Results: 126 (17%) of the 756 women delivered by CS. In multivariable analysis parity (OR 5.4), ethnicity (OR 2.4), previous miscarriage (OR 1.7), creatinine (OR 1.02), proteinuria (OR 2.4), cervical length (OR 1.02), engagement (OR 0.5) and dilatation (OR 0.7) were independent antepartum predictors. Intrapartum variables were parity (OR 3.6), ethnicity (OR 1.9), previous miscarriage (OR 1.5), gestational age at delivery (OR 1.2), antibiotic use (OR 8.0), disease progression (OR 2.4), uric acid (OR 1.4), proteinuria (OR 3.50) and dilatation (OR 0.76). Both models showed good discrimination (AUC 0.74 and 0.80) but calibration was moderate (Hosmer-Lemeshow P-value 0.42 and 0.70)., Conclusion: In women with GH or mild PE at term, the risk of CS can be predicted., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women., Methods: We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792)., Findings: Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred., Interpretation: For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered., Funding: ZonMw., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage., Design: A randomised double-blind placebo controlled multicentre trial., Patients: We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery., Setting: Delivery rooms of 11 Dutch hospitals., Intervention: When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT)., Main Outcome Measures: Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage., Results: 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2-71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8-94.7) in the CONT group (difference in median -7.69 (95% CI -24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference -16.4 (95% CI -24.6 to -1.64))., Conclusions: Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls., Trial Registration Number: NCT00189007, Dutch Trial Register NTR1383., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage., Design: Randomised non-inferiority trial., Setting: Thirty-seven Dutch university and general hospitals., Population: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities., Methods: Women were allocated to RBC transfusion or non-intervention., Main Outcome Measures: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum., Results: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable., Conclusions: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel., Design: Economic evaluation alongside a randomised controlled trial., Setting: Obstetric departments of one university and 11 teaching hospitals in the Netherlands., Population: Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section., Methods: Cost-effectiveness analysis from a hospital perspective., Main Outcome Measures: We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes., Results: Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E₂ gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction., Conclusions: Foley catheter and prostaglandin E2 labour induction generate comparable costs., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objectives. Pregnant women, referred because of an increased risk of fetal Down syndrome, who underwent an invasive prenatal procedure were offered a choice between karyotyping and rapid targeted testing. This study aims to assess women's attitudes and experiences towards what option to choose. Methods. A retrospective multicentre survey (2008-2010) was conducted among 1370 women. General questions were asked about decision making issues, followed by personal questions about their experiences in choice making, test preference, influence of others, and possible regrets. Results. In total, 90.1% of the respondents (N = 825) indicated that pregnant women are able to choose, although 33.1% stated that the choice can best be made by a professional. 18.4% indicated that making a choice places a burden on women. In 96.4%, respondents preferred to have the option to choose again in case of a next pregnancy, whereas 2.7% preferred the choice to be made by a professional. Regret was indicated by 1.2%. Decision making was influenced by others in 64.9%. A slightly higher preference for karyotyping was indicated by 52.7% of the respondents. Conclusions. Positive attitudes and experiences were expressed towards the option to choose. Respondents took decisions freely, although sometimes influenced by a partner or a professional, to follow their individual perspectives.

Objective: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram., Design: Retrospective cohort study., Setting: Three academic and six non-academic teaching hospitals in the Netherlands., Population: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation., Methods: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines., Main Outcome Measures: Number and type of ST-events., Results: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events., Conclusions: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Objective: To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians' decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term., Design: A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT)., Setting: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands., Population: A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management., Methods: Data were analysed using logistic regression modelling., Main Outcome Measures: The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes., Results: The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix., Conclusion: Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women., Trial Registration: The trial has been registered in the clinical trial register as ISRCTN08132825., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Objective: To evaluate whether correct adherence to clinical guidelines might have led to prevention of cases with adverse neonatal outcome., Design: Secondary analysis of cases with adverse outcome in a multicenter randomized clinical trial., Setting: Nine Dutch hospitals., Population: Pregnant women with a term singleton fetus in cephalic position., Methods: Data were obtained from a randomized trial that compared monitoring by STAN® (index group) with cardiotocography (control group). In both trial arms, three observers independently assessed the fetal surveillance results in all cases with adverse neonatal outcome, to determine whether an indication for intervention was present, based on current clinical guidelines., Main Outcome Measures: Adverse neonatal outcome cases fulfilled one or more of the following criteria: (i) metabolic acidosis in umbilical cord artery (pH < 7.05 and base deficit in extracellular fluid >12 mmol/L); (ii) umbilical cord artery pH < 7.00; (iii) perinatal death; and/or (iv) signs of moderate or severe hypoxic ischemic encephalopathy., Results: We studied 5681 women, of whom 61 (1.1%) had an adverse outcome (26 index; 35 control). In these women, the number of performed operative deliveries for fetal distress was 18 (69.2%) and 16 (45.7%), respectively. Reassessment of all 61 cases showed that there was a fetal indication to intervene in 23 (88.5%) and 19 (57.6%) cases, respectively. In 13 (50.0%) vs. 11 (33.3%) cases, respectively, this indication occurred more than 20 min before the time of delivery, meaning that these adverse outcomes could possibly have been prevented., Conclusions: In our trial, more strict adherence to clinical guidelines could have led to additional identification and prevention of adverse outcome., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

We sought to predict neonatal metabolic acidosis at birth using antepartum obstetric characteristics (model 1) and additional characteristics available during labor (model 2). In 5667 laboring women from a multicenter randomized trial that had a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation, we predicted neonatal metabolic acidosis. Based on literature and clinical reasoning, we selected both antepartum characteristics and characteristics that became available during labor. After univariable analyses, the predictors of the multivariable models were identified by backward stepwise selection in a logistic regression analysis. Model performance was assessed by discrimination and calibration. To correct for potential overfitting, we (internally) validated the models with bootstrapping techniques. Of 5667 neonates born alive, 107 (1.9%) had metabolic acidosis. Antepartum predictors of metabolic acidosis were gestational age, nulliparity, previous cesarean delivery, and maternal diabetes. Additional intrapartum predictors were spontaneous onset of labor and meconium-stained amniotic fluid. Calibration and discrimination were acceptable for both models (c-statistic 0.64 and 0.66, respectively). In women with a high-risk singleton term pregnancy in cephalic presentation, we identified antepartum and intrapartum factors that predict neonatal metabolic acidosis at birth., (Copyright © 2012 by Thieme Medical Publishers, Inc.)

Objective: To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress., Design: Prospective cohort study., Setting: Three academic and six non-academic teaching hospitals in the Netherlands., Population: Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation., Methods: We obtained STAN(®) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model., Main Outcome Measures: The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress., Results: From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress., Conclusion: Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods. In this prospective study 400 pregnant women undergoing amniocentesis were invited to answer a questionnaire, including information about demographic factors, current pregnancy, and previous children. In two open-ended questions they were asked why they wanted to know the fetal sex after amniocentesis or ultrasound investigation. Scores were given for reasons that could have played a role in the wish whether or not to know the sex of their unborn child. Results. A total of 210 (52.5%) questionnaires were completed. Overall, 69.0% was interested to know the fetal sex as part of the diagnostic test result. The most important reasons were curiosity (77.8%), "just want to know" (68.0%), and "because it is possible" (66.8%). The overall knowledge of sex chromosomal disorders appeared low and did not seem to affect the parent's wish to know the fetal sex. Almost all women (96.6%) planned to have a 20-week ultrasound scan and 96.2% thought the scan to be reliable in detecting the fetal sex. A minority (28%) was willing to learn the fetal sex by ultrasound examination, whereas 65% preferred to learn the fetal sex only after the amniocentesis. Conclusion. Personal values affect the parental desire to know or not to know the fetal sex. This does not appear to be affected by invasive prenatal testing and/or genetic knowledge of sex chromosomal disorders.

Objective: To evaluate whether progression to a high-risk situation is predictable in women with gestational hypertension (GH) or mild pre-eclampsia (PE) at term., Methods: Women with a singleton pregnancy, a fetus in cephalic position, between 36 and 41 weeks of gestation, complicated by GH or mild PE that were managed expectantly, were selected from the HYPITAT trial. We evaluated the predictability of progression to a high-risk situation. Logistic regression was used to determine the predictive value of clinical characteristics or laboratory findings and to generate a prediction model for progression to a high-risk situation. The predictive value of this model was assessed with receiver-operating characteristic (ROC) analysis, calibration and internal validation., Results: We included 703 women, of whom 244 (34.7%) had progression to a high-risk situation. After multivariable analysis, nulliparity (OR 1.87), maternal age (OR 1.05 per year), gestational age (OR 0.88 per week), previous abortion (OR 1.26), ethnicity (OR 2.05 for non-Caucasian ethnicity), diastolic (OR 1.04 per mmHg), systolic blood pressure (OR 1.02 per mmHg) and the laboratory parameters proteinuria, haemoglobin, platelets, uric acid and alanine aminotransferase were included in the final model. The area under the ROC curve of this model was 0.71 (95% CI, 0.67-0.74). Even though the goodness of fit was moderate (P=0.40), internal validation showed the model could hold in the overall population., Conclusion: In the prediction of progression to a high-risk situation, in women with GH or mild PE at term, a distinction can be made between women with a low risk and women with high risk., (© 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To assess the cost-effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only., Design: Cost-effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG., Setting: Obstetric departments of three academic and six general hospitals in The Netherlands. Population. Laboring women with a singleton high-risk pregnancy, a fetus in cephalic presentation, a gestational age >36 weeks and an indication for internal electronic fetal monitoring., Methods: A trial-based cost-effectiveness analysis was performed from a health-care provider perspective., Main Outcome Measures: Primary health outcome was the incidence of metabolic acidosis measured in the umbilical artery. Direct medical costs were estimated from start of labor to childbirth. Cost-effectiveness was expressed as costs to prevent one case of metabolic acidosis., Results: The incidence of metabolic acidosis was 0.7% in the ST-analysis group and 1.0% in the CTG-only group (relative risk 0.70; 95% confidence interval 0.38-1.28). Per delivery, the mean costs per patient of CTG plus ST analysis (n= 2 827) were €1,345 vs. €1,316 for CTG only (n= 2 840), with a mean difference of €29 (95% confidence interval -€9 to €77) until childbirth. The incremental costs of ST analysis to prevent one case of metabolic acidosis were €9 667., Conclusions: The additional costs of monitoring by ST analysis of the fetal ECG are very limited when compared with monitoring by CTG only and very low compared with the total costs of delivery., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: In current literature, no data on safety in pregnancy for new drugs in the treatment of multiple sclerosis (MS) like natalizumab (Tysabri®), a humanized monoclonal antibody against α4 integrins, are yet available. In the management of MS, natalizumab is the first monoclonal antibody approved to the market., Methods: We describe the pregnancy and outcome in two women with MS using natalizumab. The first patient used it in the periconceptional period, and the second patient used it in both the periconceptional period and throughout gestation., Results: The antenatal course of the first patient was complicated by an exacerbation of MS. The second patient did not experience MS relapses during pregnancy, while still using natalizumab. The newborns did not show any abnormalities postnatal and at 6 weeks' follow-up., Conclusions: This is the first detailed report on pregnancy and delivery of two babies after maternal treatment of MS with natalizumab. From the small number of cases on the usage of natalizumab during pregnancy in literature, we cannot conclude whether the use of natalizumab is safe, and long-term effects are not known. Further research is needed to establish the exact effects on pregnancy and intrauterine development as well as the long-term effects. Prenatal counseling with thorough explanation of the risks and careful decision making is advisable., (© 2010 John Wiley & Sons A/S.)

Background: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands., Methods/design: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%)., Discussion: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.

Background: Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy., Methods/design: The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis., Discussion: In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia., Trial Registration Number: Clinical Trials, protocol registration system: NCT00189007.

Objective: To evaluate the diagnostic additional value of routine alpha-foetoprotein (AFP) assessment in amniotic fluid for the detection of neural tube defects (NTDs), compared with week 20 ultrasonographic examination., Design: Retrospective., Method: We retrospectively determined AFP concentrations in amniotic fluid obtained from 7981 women who had undergone amniocentesis for karyotyping and AFP assessment. An AFP concentration greater than 2.5 times the median was considered abnormal. Women were categorised into 4 groups based on the indication for invasive prenatal diagnostic assessment: advanced maternal age (group I; n = 6179), increased risk of foetal NTDs (group II; n = 258), ultrasonographically confirmed foetal NTDs (group III; n = 55) or other indications (group IV; n = 1489)., Results: In group I, 18 of 6179 samples had increased AFP levels (0.3%), 2 of which were associated with NTDs. In group II, 2 of 258 samples had increased AFP levels (0.8%); both were associated with NTDs. Increased AFP levels were found in 44 of 55 samples from group III (80%), and 223 of 1489 samples from group IV (15.0%)., Conclusion: Routine assessment of AFP in amniotic fluid based on advanced maternal age provides little additional value in the detection of NTDs beyond that of week 20 ultrasound.

Background: Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis., Methods/design: We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options. Women in labour with a gestational age > or = 36 weeks and an indication for CTG-monitoring can be included in the trial. Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG. The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bdecf > 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals. The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied., Discussion: This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed., Trial Registration Number: ISRCTN95732366.

There is a certain degree of foetal-maternal transfusion in every pregnancy. The possibilities for using intact foetal cells extracted from maternal blood for prenatal diagnosis are limited. Recently real-time polymerase chain reaction (PCR) techniques have allowed the identification and quantification of foetal DNA in the maternal blood. Foetal sex determination with Y-chromosome-PCR has been found to have a specificity of 100%. The sensitivity is 96% but increases with gestational age, so that from 10 weeks onwards the sensitivity approaches 100%. In the case of X-linked diseases, this technique can reduce invasive prenatal diagnosis by 50%. In the case of a foetus with an elevated risk for congenital adrenal hyperplasia, early non-invasive foetal sexing can also shorten the period of maternal dexamethasone use so as to prevent virilisation in the female foetus. Early second trimester non-invasive foetal RhD genotyping with an RhD-PCR has a sensitivity and specificity of 100% each. Therefore in the future, anti-D immunoprophylaxis will be superfluous in RhD-negative women with an RhD-negative foetus. Theoretically all new and paternal inherited disorders with a known gene defect can be detected in maternal plasma. Some examples have already been described. Recently published small scale studies describe elevated concentrations of free foetal DNA in maternal plasma in (threatening) preterm labour, pre-eclampsia and aneuploidy. Large-scale studies are necessary to demonstrate the value of these findings.

Objective: To describe our clinical experience with detection and analysis of cell-free fetal DNA derived from maternal plasma for prenatal sexing and fetal rhesus-D typing., Methods: Real-time quantitative polymerase chain reactions (PCRs) of rhesus-D sequences and the SRY gene were validated and offered to patients with an enhanced risk for sex-linked fetal pathology and patients with rhesus-D antibodies., Results: In the validation group, 72 samples were analyzed. Sensitivity of the rhesus-D real-time quantitative PCR in maternal plasma was 100% (95% confidence interval [CI]91.8%, 100%) and specificity was 96.6% (95% CI 82.2%, 99.9%). Sensitivity of the SRY real-time quantitative PCR was 97.2% (95% CI 85.5%, 99.9%), and specificity was 100% (95% CI 88.1%, 100%). The technique was used successfully in a clinical setting in 24 women. Overall, invasive tests were avoided in 41.7% of these patients., Conclusion: Detection of cell-free fetal DNA from maternal plasma is a reliable technique that can substantially reduce invasive prenatal tests.

Objectives: To evaluate at what gestational age fetal DNA can reliably be detected at the earliest in maternal plasma., Methods: We performed consecutive blood sampling in the first trimester of pregnancy in 17 women who were pregnant after in vitro fertilization (IVF) or intrauterine insemination (IUI). DNA was isolated and the Y-chromosome specific SRY was amplified by real-time polymerase chain reaction (PCR). We likewise studied 31 women prior to invasive prenatal diagnosis procedures for test validation purposes. All test results were compared to cytogenetic sex or sex at birth., Results: The earliest SRY detection was at a gestational age of 5 weeks and 2 days. In none of 4 pregnancies ending in a miscarriage was SRY detected. We detected SRY in maternal plasma in 1 of 2 patients (50%) carrying a male fetus at a gestational age of 5 weeks, in 4 of 5 (80%) at a gestational age of 7 weeks, in 4 of 4 (100%) at a gestational age of 9 weeks. In all 7 women pregnant with a male fetus, the correct fetal sex was detected by 10 weeks. In none of the 6 patients who delivered a girl was SRY detected. In the validation group, SRY was detected in 13 of the 13 male, and none of the 18 female fetuses., Conclusions: We conclude that real-time PCR of the SRY gene promises to be a reliable technique for early fetal sexing in maternal plasma., (Copyright 2003 John Wiley & Sons, Ltd.)

Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal material obtained by invasive means (chorionic villus sampling or amniocentesis) are available for all clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and e) and K1 genotyping assays are discussed in this review. Importantly, one must remember that results of genotyping assays will not always be concordant with serological typing. Thus, the RhD genotyping assays have to be modified in response to increased understanding of the molecular biology of this blood group system. RhD typing assays should produce negative results when tested on the black RhD-negative RHD alleles, RHDpsi and r's. PCR-based assays can be used to determine paternal zygosity. For RhD zygosity testing, the real-time quantitative PCR approach and the direct detection of the hybrid Rhesus box, which is the result of the deletion of the RHD gene are available. Recently, methods for noninvasive prenatal genotyping have been investigated. The use of fetal cells circulating in the maternal circulation has been explored; however, the scarcity of circulating fetal cells has limited the use of this approach. More promising are the results obtained with RhD typing assays with cell-free fetal DNA, which is present in the maternal circulation in a concentration of 25 genomic equivalents per milliliter of maternal blood in early pregnancy increasing to 100 copies per milliliter in the third trimester, which is cleared from the circulation within a few hours of delivery. The positive predictive value of this approach is virtually 100%, but false-negative results are (infrequently) encountered. Therefore, this assay can at present only be used for screening of RhD-negative women to make the use of antenatal prophylaxis more targeted and hence more cost-effective. For the clinical management of the pregnancies of alloimmunized women, the development of a control for the presence and the amplification of fetal DNA is needed, which is at present only available in male pregnancies. Assays for the genotyping of the other Rh antigens or Kell antigens with cell-free fetal DNA have not yet been described., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

Objectives: Fetal pulse oximetry was performed during labor in high-risk cases for fetal distress to determine the diagnostic value of this method., Methods: The fetal SpO2 values were blinded from the obstetrician so that these values did not influence clinical decisions. Mean and lowest SpO2 measurements for the last 30 min prior to either fetal scalp blood sampling or delivery were correlated with scalp pH or pH from the umbilical artery., Results: No significant correlation was found between pH and mean fetal oxygen saturation (correlation coefficient -0.02, p = 0.9). There was no significant correlation between pH and lowest fetal oxygen saturation (correlation coefficient 0.04, p = 0.84). Concerning the feasibility of the method, we found that only 23 of 65 included patients were suitable for analysis; in 20% of cases, we were not able to perform a SpO2 measurement., Conclusions: None of three cases with pH below 7.05 would have been detected using mean SpO2 over the last 30 min prior to fetal scalp blood sampling or delivery. Only one case would have been detected using the lowest SpO2 measurement over this period. We conclude that fetal SpO2 measurements during labor are of poor diagnostic value, with a disappointing feasibility and therefore are not ready for implementing into daily clinical practice.

Objective: To determine first-trimester fetal sex by isolating free fetal DNA from maternal plasma., Methods: The index case was a pregnant woman who previously delivered a girl with congenital adrenal hyperplasia. The SRY gene as a marker for the fetal Y chromosome was detected in maternal serum and plasma by quantitative polymerase chain reaction analysis. Simultaneously, we performed the same test in 25 and 19 women in the first and second trimester, respectively, and compared plasma results with fetal gender as assessed by prenatal karyotyping or as seen at ultrasound or birth., Results: In 44 of 45 patients at gestational ages ranging from 8 3/7 to 17 3/7 weeks, we correctly predicted fetal sex using quantitative polymerase chain reaction analysis of the SRY gene in maternal plasma. In one case, the test result was inconclusive. Overall, fetal sex was correctly predicted in 97.8% of cases (95% confidence interval 88.2%, 99.9%)., Conclusion: Amplification of free fetal DNA in maternal plasma is a valid technique for predicting fetal sex in early pregnancy. In case of pregnancies at risk for congenital adrenal hyperplasia, the technique allows restriction of dexamethasone treatment to female fetuses resulting in a substantial decrease of unnecessary treatment and invasive diagnostic tests.

Objective: To determine traumatic experiences and psychological symptoms in refugees reported to the psychiatric centre De Vonk, and the relationship between biographical data, experiences of violence and post-traumatic stress symptoms on the one hand and the referral or admission policy on the other., Design: Descriptive., Setting: Centre '45, refugee unit De Vonk (department for the treatment of traumatized refugees and asylum seekers), Noordwijkerhout, the Netherlands. The psychiatric centre De Vonk comprises, apart from an outpatient clinic and a daytime clinic, a department created for the clinical treatment of refugees with symptoms related to traumatization., Methods: The main biographical and background data were collected. The first interview was routinely preceded by the Harvard trauma questionnaire (HTQ) and the Hopkins symptom checklist (HSCL-25), if necessary with the aid of an interpreter. The HTQ measures experiences of violence and post-traumatic stress symptoms; the HSCL-25 comprises an anxiety scale and a depression scale., Results: Biographical data were obtained from 232 patients and questionnaire data from 169 patients. The population was heterogeneous as regards region of origin, duration of the stay in the Netherlands, education and age. Serious forms of violence were reported, such as abuse, torture and war violence, and many symptoms of anxiety and depression were mentioned. The scores for posttraumatic stress symptoms exceeded the clinical reference values in 82% in the group examined. Of the referred patients, 37% were admitted to the clinic., Conclusion: In spite of the diversity of language, culture and education among the refugees/asylum seekers referred to De Vonk, it proved adequately possible in practice to use standardized psychological and psychiatric instruments in this group of patients. The symptom level of the patients referred was particularly high.

Posttraumatic stress disorder was diagnosed in two patients, men aged 26 and 29, an asylum seeker from the Middle East and a refugee from former Yugoslavia respectively. They had experienced severe psychotraumatic events. They were referred to a clinic for traumatised refugees and asylum seekers. Their psychiatric disturbances did not fit posttraumatic stress disorder, however. The former suffered from a schizophrenic disorder, the latter from psychosis and depression based on alcohol dependence. Growing awareness of the high prevalence of traumatic experiences in the population leads to a contextual shift in therapists regarding their understanding of the short and long term effects of traumatization in their patients. Exclusive focus on the traumatic history, however, biases the diagnostic process and could lead to wrong conclusions about a causal relationship between traumatic experiences and the psychopathology observed in the patient. When treating asylum seekers or refugees the risk of jumping to this false conclusion is even higher, partially due to cultural and language barriers.

A case of a woman having a large invasive vulvar carcinoma is reported. Because of the early age of onset and recurrent pneumonia, immunodeficiency was suspected. There appeared to be a repetitive low CD4+ T-lymphocyte count, without evidence of HIV infection or other diseases or therapies known to be clearly associated with T-cell depletion. This is suspected for the rare disorder known as idiopathic CD4+ T-lymphocytopenia which is often associated with opportunistic infections. A case of suspected idiopathic CD4+ T-lymphocytopenia in a patient having an invasive vulvar carcinoma is described.

MRI examination revealed similar brain lesions in 5 alcoholic Korsakoff patients and 5 chronic alcoholics without cognitive impairment. Not only cerebral atrophy and demyelination, but also lesions thought to be specific for the Wernicke-Korsakoff syndrome were equally prominent in both groups. The morphological abnormalities thought to be typical of Wernicke-Korsakoff syndrome are probably common features of chronic alcoholism and malnutrition. Marked atrophy of the operculae was found in all Korsakoff patients and in 3 out of 5 chronic alcoholics. Alcohol amnestic disorder may not exclusively result from diencephalic lesions, but also from temporal lesions.