Intrauterine Fetal Blood Transfusion (IUBT) for Rh Incompatibility - 12 Years' Experience from Pakistan.

OBJECTIVE: To determine the perinatal outcome of pregnancies complicated by Rh-alloimmunisation, requiring intrauterine blood transfusion. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Feto-maternal Unit of Gene Tech Laboratory, Lahore, from 2007 to 2019. METHODOLOGY: A retrospective analysis was done on the data of cases of intrauterine, intravascular blood transfusion given to at-risk foetuses to correct foetal anaemia due to Rh-alloimmunisation or parvovirus B19. All cases, who were eligible to receive IUBT were included in the study. Cases where historic data was not available have been excluded. RESULTS: A total of 305 intrauterine blood transfusion (IUBT) procedures were performed on 127 foetuses. The gestational age ranged from 18-32 weeks at the time of referral. Infra-hepatic part of umbilical vein was preferred for transfusion, but in some cases of anterior placenta, the cord insertion was approached with exception of only two cases where intra-cardiac route was employed. In this study, 71.6% of the babies survived, 14.2% were loss to follow and 14.2% died. CONCLUSION: IUBT is a safe procedure, especially when performed by experienced hands, and helps save the foetuses at risk. Mothers with Rh-alloimmunisation should be referred before developing hydrops fetalis for better outcome. Key Words: Red cell alloimmunisation, Intrauterine intravascular blood transfusion, Foetal anaemia.

MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study.

BACKGROUND: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. OBJECTIVES: To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. DESIGN: A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. SETTING: Sixteen UK fetal medicine centres. PARTICIPANTS: Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. INTERVENTIONS: Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. MAIN OUTCOME MEASURES: Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. RESULTS: The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. CONCLUSIONS: iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27626961. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.

Ultrasonography is routine in pregnancy to check that the baby's brain is developing as expected. However, no medical test is perfect and ultrasonography may miss some brain abnormalities, may get some brain abnormalities wrong or may diagnose an abnormality that is not really present. Magnetic resonance imaging (MRI) may help clarify difficult cases during pregnancy. We wanted to find out if MRI was better than ultrasonography alone in making an accurate diagnosis. We recruited pregnant women whose ultrasound scan, performed by an expert, suggested that their baby had a brain abnormality, and referred them for a MRI scan. The results of the two tests were compared with each other and to the final outcome of the pregnancy. Our results showed that using MRI in addition to ultrasonography improved the accuracy of the diagnosis in about one in four pregnancies. It changed the prediction of how the baby would develop in at least one in five cases. In many cases, the pregnancy was managed differently because of the MRI result. The MRI was acceptable to women, with 95% saying that they would have MRI again in a similar situation. Neither MRI nor ultrasonography accurately identified children who went on to have delayed development at the age of 2­3 years, but MRI was better than ultrasonography at ruling out developmental problems at this age. The MRI cost more than ultrasonography alone; therefore, whether or not it is worthwhile depends on the value placed on the decisions that changed as a result of its use.

Analysis of errors made on in utero MR studies of the foetal brain in the MERIDIAN study.

OBJECTIVES: In utero magnetic resonance (iuMR) imaging to diagnose foetal brain abnormalities has been established and is supported by meta-analyses of retrospective and prospective studies. In this paper we describe and classify the iuMR errors made in the largest diagnostic accuracy study to date (MERIDIAN). We also correlate the error rates and types with the prior experience of the reporting radiologists in order to inform how to provide a national programme with the best diagnostic accuracy achievable. METHODS: The MERIDIAN cohort of 570 foetus formed the basis of this study and included 40 cases with a confirmed diagnostic error, compared with the Outcome Reference Diagnosis. Analysis included the potential clinical effect of the error and classification of error type through an Expert Neuroradiological Panel re-reporting the study. Assessments were made regarding radiologists experience prior to MERIDIAN. RESULTS: The overall confirmed error rate for iuMR was 7·0% and it was considered that there would have been an adverse effect on prognostic information in 22/40 cases if the iuMR had informed counselling. The experienced central reporter made statistically significant fewer errors than the less experienced non-central reporters (3·8% v 11·0%) and the central reporter made fewer clinically significant errors. Furthermore, the type of cognitive errors differed between central and non-central reporters. CONCLUSIONS: Although iuMR imaging improves the diagnostic accuracy of detecting foetal brain abnormalities there remains a substantial error rate, which can have major clinical significance. We have shown that error rates are lower for more experienced reporting radiologists with fewer potential deleterious clinical implications. We discuss the implications of these findings in terms of providing a uniform national service. KEY POINTS: • Overall confirmed error rate for iuMR diagnosing foetal brain abnormalities was 7·0%. • IuMR reports had an adverse effect on counselling in 55% of error cases. • Error rates are consistently lower for more experienced radiologists. • Collaboration between radiologists, dual reporting, overseeing scan and formal training can reduce errors.

Attitudes towards non-invasive prenatal diagnosis among obstetricians in Pakistan, a developing, Islamic country.

OBJECTIVES: Stakeholders' views are essential for informing implementation strategies for non-invasive prenatal testing (NIPT). Little is known about such views in developing countries. We explored attitudes towards NIPT among obstetricians in Pakistan, a developing, Islamic country. METHODS: A 35-item questionnaire was distributed and collected at eight events (a national conference and seven workshops in five cities) for obstetric professionals on advances in fetal medicine. RESULTS: Responses from 113 obstetrician show positive attitudes towards implementation of NIPT: 95% agreed prevention of genetic conditions was a necessity, and 97% agreed public hospitals should provide prenatal screening tests. However, participants also agreed the availability of NIPT would increase social pressure on women to have prenatal screening tests and to terminate an affected pregnancy (53% and 63%, respectively). Most participants would not offer NIPT for sex determination (55%), although 31% would. The most valued aspects of NIPT were its safety, followed by its utility and then accuracy. CONCLUSION: Participants generally supported the implementation of NIPT but raised concerns about social implications. Therefore, national policy is needed to regulate the implementation of NIPT, and pretest information and post-test genetic counselling are needed to mitigate social pressure and support parents to make informed decisions. © 2017 John Wiley & Sons, Ltd.

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme.

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

OBJECTIVES: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. DESIGN: A multicentre randomised controlled trial (RCT). SETTING: Fetal medicine units. POPULATION: Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). METHODS: Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. MAIN OUTCOME MEASURES: The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. FUNDING: Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].

A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis.

BACKGROUND: Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial. METHODS: Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay. RESULTS: Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation. CONCLUSIONS: Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis.

Efficacy and safety of a new, chromatographically purified rhesus (D) immunoglobulin.

OBJECTIVES: To study the efficacy, safety, and tolerability of the 300 microg dose of a new chromatographically produced rhesus immunoglobulin (Rhophylac 300) for ante- and postnatal rhesus prophylaxis. DESIGN: In an open-label multi-centre study, rhesus D (RhD)-negative women were randomly allocated to receive Rhophylac 300 either intravenously or intramuscularly at the 28th week of gestation and within 72 h after delivery of an RhD-positive child. Serum samples were obtained prior to the antenatal dose and 6-11.5 months after delivery of an RhD-positive child and tested by the indirect antiglobulin test and papain test for anti-D. Safety parameters were assessed in all women who were treated with the study drug. RESULTS: Four hundred and thirty two women received the study drug antenatally. No differences were detected in efficacy or tolerability between intravenous and intramuscular administration. Of the 261 women who delivered an RhD-positive child and received rhesus prophylaxis according to the protocol, 248 women returned for follow-up investigations. None of them had detectable anti-D at their last visit. There were no serious adverse events, no cases of infectious disease transmission nor clinically relevant changes in laboratory safety values and vital signs attributable to the study drug. CONCLUSIONS: The results suggest that Rhophylac 300 given intravenously or intramuscularly is safe and efficacious in preventing rhesus (D) immunisation.

Symphysis pubis dysfunction--a cause of significant obstetric morbidity.

OBJECTIVES: To investigate the prevalence and severity of symphysis pubis dysfunction (SPD) in pregnancy and the postnatal period. DESIGN: A postnatal questionnaire was sent to 248 women who had been referred to the Obstetric Physiotherapy Department in 1997 and 1998 with symptoms of pubic pain either during pregnancy or soon after delivery. SETTING: A north of England teaching hospital, The Clarendon Wing, Leeds General Infirmary. PARTICIPANTS: Questionnaires were sent to 248 women. One hundred and forty-one were returned (response rate 57%). RESULTS: The condition is associated with much unrecognised obstetric morbidity. The prevalence in our unit over the 2-year study period was 1/36 women. Many medical and midwifery staff have little knowledge of SPD. Patients often felt ignored when they complained of pain. One out of four of the respondents were still symptomatic 6 months later. CONCLUSION: Further research is needed to identify the best practice in the antenatal care provided, including the provision of support belts, the most appropriate mode of delivery and postnatal treatment.