E. van den Boogaard

Treatment of thyroid disorders before conception and in early pregnancy: a systematic review

BACKGROUND Thyroid disorders are associated with pregnancy complications. Universal screening is currently not recommended because of a lack of evidence on the effectiveness of treatment. Women with hyperthyroidism and hypothyroidism evidently require treatment but this is less clear for women with subclinical hypothyroidism and thyroid autoimmunity. Therefore, we conducted a systematic review to provide a comprehensive overview on the available treatment interventions. METHODS Relevant studies were identified by searching Medline, EMBASE and Cochrane Controlled Trials Register, published until December 2011. RESULTS From a total of 7334 primary selected titles, 22 articles were included for the systematic review and 11 were appropriate for meta-analyses. Eight studies reported on hyperthyroidism. Propylthiouracil (PTU) and methimazole reduce the risk for preterm delivery [risk ratio (RR): 0.23, confidence interval (CI): 0.1-0.52], pre-eclampsia (RR: 0.23, CI: 0.06-0.89) and low birthweight (RR: 0.38, CI: 0.22-0.66). The nine studies that reported on clinical hypothyroidism showed that levothyroxine is effective in reducing the risk for miscarriage (RR: 0.19, CI: 0.08-0.39) and preterm delivery (RR: 0.41, CI: 0.24-0.68). For treatment of subclinical hypothyroidism, current evidence is insufficient. The five studies available on thyroid autoimmunity showed a not significant reduction in miscarriage (RR: 0.58, CI: 0.32-1.06), but significant reduction in preterm birth by treatment with levothyoxine (RR: 0.31, CI: 0.11-0.90). CONCLUSION For hyperthyroidism, methimazole and PTU are effective in preventing pregnancy complications. For clinical hypothyroidism, treatment with levothyroxine is recommended. For subclinical hypothyroidism and thyroid autoimmunity, evidence is insufficient to recommend treatment with levothyroxine. The overall lack of evidence precludes a recommendation for universal screening and is only justified in a research setting.

Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier status?

BACKGROUND Carrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality. METHODS A nested case-control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status. RESULTS Two hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89%) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48-1.7] or three (OR 0.71, 95% CI 0.39-1.3) non-consecutive miscarriages. CONCLUSIONS The sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.

Development of guideline-based quality indicators for recurrent miscarriage

Recurrent miscarriage (RM) is a multifactorial clinical problem. Guidelines have been published to guide evidence-based clinical practice in RM. To measure adherence to these guidelines in daily practice and to monitor quality of care delivered in RM patients, indicators are necessary. This study aimed to develop a set of valid quality indicators for RM and to explore the relationship between evidence level of guideline recommendations and their acceptance rate as quality indicators. Expert opinions of 11 gynaecologists were used to appraise all guideline recommendations. The systematic RAND-modified Delphi method was used to develop the indicator set from the Dutch guideline on RM. The acceptance rate as indicator of the initial recommendations was assessed per evidence level. A representative set of 23 key recommendations was selected out of 39 guideline recommendations, covering diagnostic tests, lifestyle, therapy and counselling. All recommendations of evidence level A (high) and D (consensus based) were accepted as indicators, while 64% of level B and 22% of level C was accepted. In conclusion, this study generated a set of 23 quality indicators for care in couples with RM. The selection of all consensus-based recommendations subscribes the general importance of these recommendations for gynaecologists.

Guideline adherence in ectopic pregnancy management

BACKGROUND Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

Selective karyotyping in recurrent miscarriage: are recommended guidelines adopted in daily clinical practice?

BACKGROUND Couples with recurrent miscarriage (RM) have an increased risk of one of the partners carrying a structural chromosome abnormality. On the basis of four independent risk factors, an evidence-based model was developed, which allows limiting karyotyping to high-risk couples. The aim of this study was to assess the level of adoption of selective karyotyping, its clinical consequences and the factors at the patient and hospital level that determine adoption. METHODS A retrospective cohort study was performed in nine Departments of Obstetrics and Gynaecology, the Netherlands, in 2006. Selective karyotyping was defined as offering karyotyping to high-risk couples and refraining from karyotyping in low-risk couples. Data were collected for risk factors as described in the model for selective karyotyping, cytogenetic results as a measure for clinical consequences, and information about determinants and costs. RESULTS A total of 530 couples were included; 252 (48%) high-risk couples and 278 (52%) low-risk couples. Among the high-risk couples, 186 (74%) were offered karyotyping. Although not advised, karyotyping was still performed in 198 (71%) low-risk couples. Overall, selective karyotyping was offered to 50% of the couples. The main determinants for adoption of the model were maternal age, obstetric history, treatment by specialists in RM and the number of patients per centre. If selective karyotyping was adopted adequately, a potential reduction of 34% of all karyotyping tests performed is possible. CONCLUSION Selective karyotyping is applied in only half of the couples with RM in daily practice. Implementation of selective karyotyping should be a topic of future research.

Recurrent miscarriage: do professionals adhere to their guidelines

STUDY QUESTION Is the actual care for recurrent miscarriage in clinical practice in accordance with 23 guideline-based quality indicators? SUMMARY ANSWER The accordance of actual care with the guidelines was poor and there is evident room for improvement. WHAT IS KNOWN ALREADY Evidence-based guidelines are important instruments to improve quality of care, but implementation of guidelines is often problematic. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was performed within a 12-month period (2006) in nine departments of Obstetrics and Gynaecology in the Netherlands. PARTICIPANTS, SETTING, METHODS Five hundred and thirty women with recurrent miscarriage were included. Actual care was assessed with 23 guideline-based quality indicators (covering diagnostics, therapy and counselling) by calculating per indicator the percentage of women for whom the indicator was followed. Thereafter we did multilevel analyses, to relate the adherence to the indicator to determinants of women, professionals and hospitals. MAIN RESULTS AND THE ROLE OF CHANCE Homocysteine and antiphospholipid antibodies were determined in 39 and 47%, respectively. Thrombophilia screening (54%) and karyotyping (50%) were offered to women regardless of their underlying risk for inherited thrombophilia or chromosome abnormalities. Higher maternal age at the time of presentation and a lower number of preceding miscarriages were improperly used to decide on diagnostic tests and were both associated with lower guideline adherence by professionals. Professionals with a subspecialization in recurrent miscarriage performed better standard care, i.e. screening for antiphospholipid antibodies and homocysteine, but also showed overuse of diagnostics in women at low risk of inherited thrombophilia. LIMITATIONS, REASONS FOR CAUTION Retrospective cohort study. WIDER IMPLICATIONS OF THE FINDINGS Quality indicators used will enable measurement of quality of care. STUDY FUNDING The study was funded by The Netherlands Organisation for Health Research and Development (ZonMw) (Grant no. 94517005). None of the authors has any conflict of interest to declare.

Reply: Recurrent miscarriage: guidelines could be improved

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