Ellen Knox

Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence

Objectives To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth. Study selection Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes. Data synthesis Odds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model. Results 30 articles with 31 studies (19 cohort and 12 case-control) involving 12 126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12 566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P<0.001). For case-control studies the odds ratio for miscarriage was 1.80, 1.25 to 2.60; P=0.002). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01). Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48, 0.25 to 0.92; P=0.03). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31, 0.11 to 0.90). Conclusion The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

Effectiveness of nifedipine versus atosiban for tocolysis in preterm labour: a meta-analysis with an indirect comparison of randomised trials

Objective To explore the effectiveness of nifedipine compared with atosiban for tocolysis in preterm labour.

In-utero pulmonary drainage in the management of primary hydrothorax and congenital cystic lung lesion: a systematic review

To determine the effect of in‐utero pulmonary drainage on perinatal survival in fetuses with primary hydrothoraces and/or congenital cystic lung lesions.

Prenatal detection of pulmonary hypoplasia in fetuses with congenital diaphragmatic hernia: A systematic review and meta-analysis of diagnostic studies

Background. Fetuses with congenital diaphragmatic hernia (CDH) are at risk of death from pulmonary hypoplasia at birth. Objective. To determine the value of prenatal imaging parameters for predicting lethal pulmonary hypoplasia in fetuses with CDH. Search strategy. Relevant papers were identified by searching MEDLINE (1966–2008), EMBASE (1988–2008) and the Cochrane Library (2008 issue 3). Selection criteria. Selected studies examined diagnostic tests for the prenatal prediction of lethal pulmonary hypoplasia in fetuses with CDH. The primary outcome measure was perinatal survival. Results.  Twenty-one studies fulfilled the entry criteria, of which six examined entirely unique heterogeneous parameters and the remaining 15 examined lung–head ratios (LHR) and/or the presence of liver in the fetal thorax. The strongest association was that of LHR ≥ 0.6 compared to <0.6 (OR: 17.02; 95% CI: 2.10–137.89), although more clinically relevant was that of LHR >1.0 (OR: 5.07; 95% CI: 2.94–8.74). The finding of liver in the fetal chest was a poor prognostic feature (survival OR: 0.32; 95% CI: 0.21–0.49). Conclusion. In CDH, LHR and the presence of liver in the fetal thorax may be a useful predictive indicator of perinatal survival. Future usage of developing techniques needs careful evaluation prior to usage to guide therapy.

The accuracy of various tests for bacterial vaginosis in predicting preterm birth: a systematic review

Objective  To determine the accuracy with which various types of tests for bacterial vaginosis predict spontaneous preterm birth in pregnant women.

The usefulness of nimodipine, an L-calcium channel antagonist, in the treatment of tinnitus

Thirty-one patients were drawn from a tinnitus clinic, screened for other medical problems and treated for 4 weeks with 30 mg nimodipine four times daily. Before and after treatment, the intensity of their tinnitus was assessed subjectively on a scale 1-10. Five patients reported to have a great improvement in their tinnitus whilst two claimed a worsening of the condition. Of the five positive responders, four were treated further with 30 mg nimodipine per day for 4 weeks and 60 mg per day for a further 4 weeks. During this treatment they were assessed more objectively by the determination of the minimal masking level using narrow band noise. There was a good correlation between the subjective and objective assessment of their responses.

A review of the methodological features of systematic reviews in fetal medicine

Systematic reviews of fetal medicine can serve as a tool for translation of research findings from a few expert centres to a wider healthcare specialty. The extent to which reviews of fetal medicine research are systematic and unbiased is not known. In this review of systematic reviews in fetal medicine, we have searched without language restrictions, Medline, Embase, DARE (Database of Abstracts of Reviews of Effectiveness), Cochrane Library (from database inception to 2005) and bibliographies of known reviews, and contacted experts to identify potentially relevant citations of literature for reviews of fetal medicine studies. The selected reviews were assessed for information on framing of questions, literature search and methods of review. The search yielded 659 citations of which 84 reviews met the inclusion criteria. Most of the reviews were in the field of fetal pathology (49/84, 59%). A majority of reviews (58/84, 69%) specified the question to be answered but only half (44/84, 52%) addressed a focussed question. Although 57/84 (68%) reviews had a detailed search description, only 32/84 (38%) searched without language restriction. 45/84 (54%) searched in multiple databases and 27/84 (32%) assessed for the risk of missing studies. There was no difference in quality between reviews of fetal pathology, screening for aneuploidy, fetal growth and fetal therapy, except with respect to specifying the question (p<0.03), search without language restriction (p<0.004), assessment of risk of missing studies (p<0.006) and study quality assessment (p<0.002) where reviews of fetal growth performed better than other domains. Our study reflects the paucity of good quality reviews in fetal medicine research. Existing reviews tend to be poor in reporting methodological features. Particularly, not enough attention is paid to assessment of validity of included studies and means to improving reliability of results through appropriate use of meta-analysis. There is a need for conducting further reviews and for rigour when reviewing fetal medicine research.

The accuracy of various tests for bacterial vaginosis in predicting preterm birth—a systematic review

To determine the accuracy with which various types of tests for bacterial vaginosis (BV) predict spontaneous preterm birth in pregnant women, studies were identified, without language restrictions, through nine different databases and manual searching of bibliographies of known primary and review articles. There are four different BV testing methods: Gram-staining test using either Nugents or Spiegels criteria, gas liquid chromatography and clinical criteria. Two reviewers selected studies independently and extracted data on their characteristics, quality and accuracy with spontaneous preterm birth as the reference standard. Data on asymptomatic women and women with symptoms of threatened preterm labour were analysed separately. Data were pooled to produce summary estimates of likelihood ratios for positive (LR+) and negative (LR−) test results for the various types of tests. There were 18 primary articles, involving a total of 17 868 women. Meta-analysis of studies testing asymptomatic women in the second trimester showed that clinical criteria had an LR+ of 5.14 (95% confidence interval 4.44–6.15) and an LR− of 0.48 (0.42–0.55), Gram-staining (Nugents criteria) had an LR+ of 1.64 (1.44–1.87) and an LR− of 0.88 (0.84–0.92), and Gram-staining (Spiegels criteria) had an LR+ of 2.44 (1.36–4.98) and an LR− of 0.81 (0.64 to 1.01). Among symptomatic women, Gram-staining (Spiegels criteria) had an LR+ of 1.29 (1.03–1.62) and an LR− of 0.85 (0.73–1.00).