Andrew Breeze

Abstract The aim of this study was to determine whether women induced for obstetric cholestasis (OC) have increased rates of operative delivery compared with women without OC who are induced. This retrospective case-control study included 64 women with OC ( ...

Gonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003). Unfortunately the low oestrogen state that they induce is associated with adverse effects including an acceleration in bone mineral density (BMD) loss. To determine the effect of treatment with gonadotrophin-releasing hormone analogues (GnRHas) on the bone mineral density of women with endometriosis, compared to placebo, no treatment, or other treatments for endometriosis, including GnRHas with add-back therapy. We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials (23rd October 2002) and the Cochrane Central Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 - March Week 2 2003). We also searched the reference lists of articles and contacted researchers in the field. Prospective, randomised controlled studies of the use of GnRHas for the treatment of women with endometriosis were considered, where bone density measurements were an end point. The control arm of the studies was either placebo, no treatment, another medical therapy for endometriosis, or GnRHas with add-back therapy. Two reviewers (JF and MS) independently assessed trial quality and extracted data. Study authors were contacted for additional information. Thirty studies involving 2,391 women were included, however only 15, involving 910 women, could be included in the meta-analysis. The meta-analysis showed that danazol and progesterone + oestrogen add-back are protective of BMD at the lumbar spine both during treatment and for up to six and twelve months after treatment, respectively. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after six months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after six months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRH analogues (SMD 0.15, 95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back, that is oestrogen + progesterone or oestrogen only, there was a significantly bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21). These numbers reflect the absolute value measurements at the lumbar spine after six months of treatment. Due to the small number of studies in the comparison we are unable to conclude whether calcium-regulating agents are protective. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill (OCP) or progestagens were identified. Both danazol and progesterone + oestrogen add-back have been shown to be protective of BMD, while on treatment and up to six and 12 months later, respectively. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Studies of danazol versus GnRHa did not report long-term follow-up. The significant side effects associated with danazol limit its use.

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > ...

To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality. Prospective self-completion questionnaire. UK fetal medicine and delivery unit. 35 women and their partners after second or third trimester pregnancy loss, making decisions about having a postmortem. Participants were asked to complete a questionnaire about postmortem decision-making which included questions about their attitudes to taking part in research. Prior to giving full approval for the study, the Research Ethics Committee (REC) requested feedback after 10 questionnaires had been returned. Responses from the first 10 participants were positive about the research and the REC allowed the study to continue. 31 questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Of the 22 participants who answered a question about the impact of participating in this research, 73% stated that completing the questionnaire had helped them feel better about the decision whether or not to consent to postmortem and none reported any adverse effect of completing the questionnaire. Additional comments made by 19 participants supported this finding. Research into this sensitive area of perinatal medicine where there is a poor outcome is possible and is indeed well received by many parents. RECs should not automatically take a negative stance towards studies of this type.

ObjectivesAutopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy.Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy.MethodsForty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the ‘gold standard’. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy.Forty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the ‘gold standard’. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy.ResultsIn 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance.In 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance.ConclusionsAlthough in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.Although in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

ObjectivesFollowing perinatal death, organ weights at autopsy may provide evidence of growth restriction and pulmonary hypoplasia. Whilst postmortem magnetic resonance imaging (MRI) may provide comparable information to autopsy about structural abnormalities, its ability to provide reproducible data about organ size has yet to be determined. We examined the feasibility of using postmortem MRI to provide estimates of organ size and weight.Following perinatal death, organ weights at autopsy may provide evidence of growth restriction and pulmonary hypoplasia. Whilst postmortem magnetic resonance imaging (MRI) may provide comparable information to autopsy about structural abnormalities, its ability to provide reproducible data about organ size has yet to be determined. We examined the feasibility of using postmortem MRI to provide estimates of organ size and weight.MethodsTwenty-five fetuses of gestational age from 16 to 40 weeks underwent postmortem MRI prior to autopsy. Fetal lung, brain and liver volume estimations were performed by two observers using the stereology technique on postmortem MRI slices. Fetal lung, brain and liver weights were recorded at autopsy. Organ volume estimates and autopsy organ weights were compared using regression analysis, and estimates of fetal organ densities made. Interobserver variability was assessed using a Bland–Altman plot. Receiver–operating characteristics curve (ROC) analysis compared MRI brain : liver volume ratios to autopsy brain : liver weight ratios.Twenty-five fetuses of gestational age from 16 to 40 weeks underwent postmortem MRI prior to autopsy. Fetal lung, brain and liver volume estimations were performed by two observers using the stereology technique on postmortem MRI slices. Fetal lung, brain and liver weights were recorded at autopsy. Organ volume estimates and autopsy organ weights were compared using regression analysis, and estimates of fetal organ densities made. Interobserver variability was assessed using a Bland–Altman plot. Receiver–operating characteristics curve (ROC) analysis compared MRI brain : liver volume ratios to autopsy brain : liver weight ratios.ResultsA linear relationship between organ volume estimates and organ weight was observed. Estimated densities for the fetal brain, liver and lung were 1.08 g/cm3, 1.15 g/cm3 and 1.15 g/cm3, respectively. Interobserver 5th and 95th percentile limits of agreement for fetal brain, liver and lung were − 5.4% to + 7.9%, − 11.8% to + 8.3% and − 14.3% to + 8.7%, respectively. For MRI organ volumes to detect a brain weight : liver weight ratio ≥ 4, ROC analysis demonstrated an area under the curve of 0.61, with an optimal cut-off of 4.1.A linear relationship between organ volume estimates and organ weight was observed. Estimated densities for the fetal brain, liver and lung were 1.08 g/cm3, 1.15 g/cm3 and 1.15 g/cm3, respectively. Interobserver 5th and 95th percentile limits of agreement for fetal brain, liver and lung were − 5.4% to + 7.9%, − 11.8% to + 8.3% and − 14.3% to + 8.7%, respectively. For MRI organ volumes to detect a brain weight : liver weight ratio ≥ 4, ROC analysis demonstrated an area under the curve of 0.61, with an optimal cut-off of 4.1.ConclusionPostmortem MRI organ volumetry can be used to estimate weights of major fetal organs. This may increase the information obtained from a minimally-invasive perinatal autopsy, particularly in the context of pulmonary hypoplasia and intrauterine growth restriction, where differential organ growth plays a major part in assessment of the underlying pathology. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.Postmortem MRI organ volumetry can be used to estimate weights of major fetal organs. This may increase the information obtained from a minimally-invasive perinatal autopsy, particularly in the context of pulmonary hypoplasia and intrauterine growth restriction, where differential organ growth plays a major part in assessment of the underlying pathology. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

ObjectivesTo determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan.To determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan.MethodsA prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 19–46). Women were offered NT screening at 11 to 14 weeks. Those with NT ≥3 mm were offered chorionic villus sampling. Those declining CVS, and those with NT <3 mm, were offered early triple tests. Women with a term combined risk of trisomy 21 ≥ 1:250, based on age, NT, and triple test results were offered amniocentesis.A prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 19–46). Women were offered NT screening at 11 to 14 weeks. Those with NT ≥3 mm were offered chorionic villus sampling. Those declining CVS, and those with NT <3 mm, were offered early triple tests. Women with a term combined risk of trisomy 21 ≥ 1:250, based on age, NT, and triple test results were offered amniocentesis.ResultsUsing a 3-mm NT ‘cut-off’ identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9). Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%) had a ≥ 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to achieve an 88% detection rate using the triple test alone, the predicted FPR would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the detection rate would be only 60%.Using a 3-mm NT ‘cut-off’ identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9). Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%) had a ≥ 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to achieve an 88% detection rate using the triple test alone, the predicted FPR would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the detection rate would be only 60%.ConclusionIn a high-risk group, the combination of NT with triple test offers detection of trisomy 21 at least equivalent to either test, while allowing disclosure of an abnormal NT at the scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably lower than expected for triple test alone for this population. Copyright © 2005 John Wiley & Sons, Ltd.In a high-risk group, the combination of NT with triple test offers detection of trisomy 21 at least equivalent to either test, while allowing disclosure of an abnormal NT at the scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably lower than expected for triple test alone for this population. Copyright © 2005 John Wiley & Sons, Ltd.

With changes in antenatal screening, and improvements in ultrasound technology, an increasing number of fetal anomalies are detected, and often earlier in pregnancy than was once the case. This is especially true for chromosomal abnormalities. The National Screening Committee has made recommendations about fetal anomaly screening in the UK, and the standards that it expects maternity services to meet.Clinicians should be aware that not all anomalies can be detected early in pregnancy, and that late diagnoses of major structural and chromosomal anomalies continue to be made.