Placental architectural characteristics following laser ablation within monochorionic twins complicated by twin-twin transfusion syndrome: A systematic review and meta-analysis of outcomes.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) complicates approximately 10%-15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental architectural characteristics within TTTS twins following laser and elucidate their impact on fetal outcomes and operative success. MATERIAL AND METHODS: Five databases were searched from inception to August 2023. Studies detailing post-delivery placental analysis within TTTS twins post-laser were included. Studies were categorized into two main groups: (1) residual anastomoses following laser and (2) abnormal cord insertion: either velamentous and/or marginal or proximate. The primary outcome was to determine the proportion of TTTS placentas with residual anastomoses and abnormal cord insertions post-laser. Secondary outcomes included assessing residual anastomoses on post-laser fetal outcomes and assessing the relationship between abnormal cord insertion and TTTS development. Study bias was critiqued using the Joanna Briggs Institute checklists and Cochrane risk of bias tool. Random-effects meta-analysis was used, and results were reported as pooled proportions or odds ratio (OR) with 95% confidence interval (CI). PROSPERO registration: CRD42023476875. RESULTS: Twenty-six studies, comprising 4013 monochorionic twins, were included for analysis. The proportion of TTTS placentas with residual anastomoses following laser was 24% (95% CI, 0.12-0.41), with a mean and standard deviation of 4.03 ± 2.95 anastomoses per placenta. Post-laser residual anastomoses were significantly associated with intrauterine fetal death (OR, 2.38 [95% CI, 1.33-4.26]), neonatal death (OR, 3.37 [95% CI, 1.65-6.88]), recurrent TTTS (OR, 24.33 [95% CI, 6.64-89.12]), and twin anemia polycythemia sequence (OR, 13.54 [95% CI, 6.36-28.85]). Combined abnormal cord (velamentous and marginal), velamentous cord, and marginal cord insertions within one or both twins following laser were reported at rates of 49% (95% CI, 0.39-0.59), 27% (95% CI, 0.18-0.38), and 28% (95% CI, 0.21-0.36), respectively. Combined, velamentous and marginal cord insertions were not significantly associated with TTTS twins requiring laser (p = 0.72, p = 0.38, and p = 0.71, respectively) versus non-TTTS monochorionic twins. CONCLUSIONS: To the best of our knowledge, this is the first review to conjointly explore outcomes of residual anastomoses and abnormal cord insertions within TTTS twins following laser. A large prospective study is necessitated to assess the relationship between abnormal cord insertion and residual anastomoses development post-laser.

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

Authors' reply to: Letter to the Editor in response to 'Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study'.

In this correspondence we thank the authors for highlighting the importance of our work, and agree with the limitations they have raised regarding performing this study.

Women's perspectives on caesarean section recovery, infection and the PREPS trial: a qualitative pilot study.

BACKGROUND: In England, 27.8% of all pregnant women undergo caesarean sections (CS) to deliver their babies. Women undergoing CS are at risk of developing sepsis and post-natal infections, which not only contribute significantly to maternal mortality and morbidity, but also negatively impact upon post-natal recovery and wellbeing. This study explores patients' priorities in relation to CS recovery, focusing on their knowledge and experiences of infection prevention. The study formed part of the PREPS (Vaginal Preparation at caesarean section to Reduce Endometritis and Prevent Sepsis - a feasibility study of chlorhexidine) Trial; patients' views on the PREPS Trial were also sought. METHODS: Using qualitative methodology, two focus groups and six telephone interviews were carried out between September and October 2017 with a total of 21 women who had undergone a CS within the preceding six months. Focus groups and individual telephone interviews were audio-recorded and transcribed verbatim; a thematic analysis was conducted using NVivo 11. RESULTS: Women's priorities around CS recovery centred on pain (or the lack thereof), mobility and the ability to resume everyday activities, including caregiving. Those undergoing a CS for the first time reported not feeling confident in their ability to identify signs of infection and sought visiting health professionals' expertise and reassurance. Women were unable to recall whether they had received information regarding infection prevention and felt that they had not received sufficient advice. Some reported receiving general information regarding CS recovery, which ranged in quality. Prevention of womb infection is a major goal of the PREPS trial, however, the majority of women were not aware that womb (as opposed to wound) infection was a post CS risk. CONCLUSIONS: Women undergoing a CS want more information on what constitutes a 'normal' post-operative recovery and specifically would welcome written information and infection prevention advice. This should be a key element of improving post-CS maternal experiences and potentially reducing sepsis and infection rates. CS stigma negatively impacts women's recovery experiences and possibly information provision. The PREPS team incorporated findings regarding consent pathways for recruiting women into intrapartum research and developed two patient reported outcomes to collect in the main trial. TRIAL REGISTRATION: The PREPS trial has been registered with ISRCTN on the 10th July 2017 ( ISRCTN33435996 ).

Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study.

BACKGROUND: Twin-twin transfusion syndrome (TTTS) is a highly morbid condition in which treatment exists, but the pregnancy remains high-risk until delivery. It may have serious sequelae, including fetal death, and in the longer term, neurodevelopmental problems. The aim of this study is to assess antenatal and postnatal parental attachment and depressive symptoms in those with pregnancies affected by TTTS. METHODS: Couples attending for fetoscopic laser ablation treatment of TTTS were asked to complete Condon's Maternal/Paternal Antenatal/Postnatal Attachment Scale as appropriate, and the Edinburgh Depression Scale the day before ablation, 4 weeks post-ablation, and 6-10 weeks postnatally. RESULTS: 25/27 couples completed the pre-ablation questionnaire (median gestational age 19 + 3 weeks [interquartile range 18 + 2-20 + 6]). 8/18 eligible couples returned the post-ablation questionnaire. 5/17 eligible couples returned the postnatal questionnaire. There was no significant difference in parento-fetal attachment when mothers were compared to fathers at each time point, however parento-fetal attachment did increase over time in mothers (p = 0.004), but not fathers. Mothers reported more depressive symptoms antenatally compared to fathers (p < 0.02), but there was no difference postnatally. 50% women reported Edinburgh Depression Scale scores above the cut-off (≥15) 4 weeks post-ablation. Over time maternal depressive symptoms decreased (p = 0.006), however paternal depressive symptoms remained the same. CONCLUSIONS: This is the first attachment and depression study in a UK cohort of parents with pregnancies affected by TTTS. Although this was a small cohort and the questionnaires used had not been validated in these circumstances, the results suggest that centres caring for these couples should be aware of the risk of maternal and paternal antenatal depression, and screen and refer for additional psychological support. Further work is needed in larger cohorts. TRIAL REGISTRATION: ISRCTN 13114861 (retrospectively registered).

Early prognostic factors of outcomes in monochorionic twin pregnancy: systematic review and meta-analysis.

BACKGROUND: Monochorionic twin pregnancies are high-risk, however at present, no screening test is available to predict which monochorionic twin pregnancy will develop complications. OBJECTIVE: We sought to assess ability of first-trimester pregnancy-related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies. DATA SOURCES: Data sources were MEDLINE, Embase, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to May 12, 2017. Gray literature and bibliographies of articles were checked. STUDY ELIGIBILITY CRITERIA: Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic-diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed, were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Quality assessment was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I2 and publication bias was visually assessed by funnel plots and quantitatively by Egger test. RESULTS: In all, 48 studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: nuchal translucency >95th centile in one/both fetuses and twin-twin transfusion syndrome (odds ratio, 2.29 [95% confidence interval, 1.05-4.96], I2 = 6.6%, 4 studies, 615 pregnancies); crown-rump length discordance ≥10% and twin-twin transfusion syndrome (odds ratio, 2.43 [95% confidence interval, 1.13-5.21], I2 = 14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and twin-twin transfusion syndrome (odds ratio, 2.12 [95% confidence interval, 1.17-3.83], I2 = 0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation. CONCLUSION: It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first-trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors.

Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis.

OBJECTIVES: To determine association, and predictive ability, of first trimester maternal serum pregnancy associated plasma protein A (PAPP-A) with adverse pregnancy outcomes. METHOD: Searches of Medline, Embase and CINAHL (inception September 2015) for studies including pregnant women with first trimester PAPP-A and assessment of pregnancy outcomes. Study characteristics, quality and results extracted. Meta-analysis of odds ratios (ORs), and likelihood ratios (LRs) and 95% confidence intervals (CI). RESULTS: Thirty-two studies including 175 240 pregnancies. PAPP-A <5th centile had a moderate association with: birth weight <10th centile OR 2.08 (95% CI 1.89-2.29), <5th centile OR 2.83 (95% CI 2.52-3.18); pre-eclampsia OR 1.94 (95% CI 1.63-2.30), preterm birth <37 weeks OR 2.09 (95% CI 1.87-2.33), and composite adverse outcome OR 3.31 (95% CI 1.80-5.11). The predictive ability was poor: Birth weight <10th centile LR + ve 1.96 (95% CI 1.58-2.43), LR-ve 0.93 (95% CI 0.89-0.98); birth weight <5th centile LR + ve 2.65 (95% CI 2.35-2.99), LR-ve 0.85 (95% CI 0.74-0.98); PTB <37 weeks LR + ve 1.84 (95% CI 1.41-2.39), LR-ve 0.92 (95% CI 0.87-0.98). CONCLUSIONS: First trimester low maternal serum PAPP-A is associated with adverse pregnancy outcome, but predictive values are poor. Further work should address PAPP-A as a continuous variable in combination with other prognostic markers as a prediction model. © 2016 John Wiley & Sons, Ltd.

The prediction, diagnosis and management of complications in monochorionic twin pregnancies: the OMMIT (Optimal Management of Monochorionic Twins) study.

BACKGROUND: Monochorionic twin pregnancies are at increased risk of complications due to sharing a single placenta and potentially developing unbalanced vascular anastomoses. Complications include twin-twin transfusion syndrome (TTTS) which affects 10-15% monochorionic twins, and if untreated has a 70-90% perinatal loss rate. We are currently unable to predict which twins will develop complications or to what severity. We have previously shown differences in angiogenic and placental growth factors in maternal blood in pregnancies complicated by TTTS compared to twin pregnancies not complicated by TTTS but matched for gestation. There is also evidence to suggest that abnormal ultrasound measurements recorded in the first trimester (nuchal translucency and crown-rump length) may be associated with severe TTTS later in pregnancy, however the detection rate is only reported as 52%. We hypothesize that if these changes precede the development of the clinical syndrome, this may increase the sensitivity and specificity of detecting adverse pregnancy outcomes. METHODS: This cohort study has retrospective and prospective elements. In the retrospective cohort we will measure factors (decided based on preliminary work and a systematic review and meta-analysis) in stored maternal blood samples taken in the first-trimester, extract first-trimester ultrasound measurements and match these to pregnancy outcome. The prospective cohort will be divided into a "screening" cohort and "complicated" cohort. The screening cohort will undergo serial maternal blood sampling at 12, 16 and 20 weeks; we will extract ultrasound measurements and match to pregnancy outcome. The complicated cohort will comprise of women referred to the Fetal Medicine Centre with complications of monochorionicity. If the decision is taken to undergo fetoscopic laser ablation we will take maternal blood samples and amniotic fluid samples pre- and post-laser treatment. The same factors will be measured in the prospective cohort as informed by the retrospective study. DISCUSSION: This study aims to increase knowledge surrounding the pathology of complications in monochorionic twins, to aid future diagnosis and management. TRIAL REGISTRATION: ISRCTN 13114861 (retrospectively registered).

Fetal Brain Injury in Survivors of Twin Pregnancies Complicated by Demise of One Twin: A Review.

Perinatal mortality is increased considerably in multiple pregnancies compared to singleton pregnancies, with single intrauterine fetal demise (sIUFD) presenting a rare but unique perinatal problem. Monochorionic pregnancies are at particular risk of sIUFD due to bidirectional inter-twin placental vascular anastomoses. The resulting inter-twin blood flow can become unbalanced, causing acute and chronic inter-twin transfusion and profound anemia secondary to fetal exsanguination into the low-pressure circulation of the dead fetus. If the sIUFD occurs after 14 weeks' gestation it is believed to have the most significant effect on the continuing pregnancy as the co-twin is at increased risk of preterm delivery, long-term neurological complications, and death. This article will focus on fetal brain injury in the surviving co-twin in the case of sIUFD, as it is the most common kind of injury in sIUFD, and one which concerns parents and may be the basis for terminating the pregnancy. We will outline how these brain injuries are thought to occur and describe potential pathophysiological mechanisms. We will discuss risk factors for brain injury in cases of sIUFD, including: chorionicity, cause of the sIUFD (spontaneous or secondary to an underlying pathological process such as twin-to-twin transfusion syndrome), gestation of delivery and how to prevent brain injury in the co-twin. We also review modes of imaging, discuss the difficulties in predicting the long-term outcome for co-twin survivors, and highlight the dearth of research in this area.

Induction of labour care in the UK: A cross-sectional survey of maternity units.

OBJECTIVES: To explore local induction of labour pathways in the UK National Health Service to provide insight into current practice. DESIGN: National survey. SETTING: Hospital maternity services in all four nations of the UK. SAMPLE: Convenience sample of 71 UK maternity units. METHODS: An online cross-sectional survey was disseminated and completed via a national network of obstetrics and gynaecology specialist trainees (October 2021-March 2022). Results were analysed descriptively, with associations explored using Fisher's Exact and ANOVA. MAIN OUTCOME MEASURES: Induction rates, criteria, processes, delays, incidents, safety concerns. RESULTS: 54/71 units responded (76%, 35% of UK units). Induction rate range 19.2%-53.4%, median 36.3%. 72% (39/54) had agreed induction criteria: these varied widely and were not all in national guidance. Multidisciplinary booking decision-making was not reported by 38/54 (70%). Delays reported 'often/always' in hospital admission for induction (19%, 10/54) and Delivery Suite transfer once induction in progress (63%, 34/54). Staffing was frequently reported cause of delay (76%, 41/54 'often/always'). Delays triggered incident reports in 36/54 (67%) and resulted in harm in 3/54 (6%). Induction was an area of concern (44%, 24/54); 61% (33/54) reported induction-focused quality improvement work. CONCLUSIONS: There is substantial variation in induction rates, processes and policies across UK maternity services. Delays appear to be common and are a cause of safety concerns. With induction rates likely to increase, improved guidance and pathways are critically needed to improve safety and experience of care.

Mothers working to prevent early stillbirth study (MiNESS 20-28): a case-control study protocol.

INTRODUCTION: In the UK, 1600 babies die every year before, during or immediately after birth at 20-28 weeks' gestation. This bereavement has a similar impact on parental physical and psychological well-being to late stillbirth (>28 weeks' gestation). Improved understanding of potentially modifiable risk factors for late stillbirth (including supine going-to-sleep position) has influenced international clinical practice. Information is now urgently required to similarly inform clinical practice and aid decision-making by expectant mothers/parents, addressing inequalities in pregnancy loss between 20 and 28 weeks. METHODS AND ANALYSIS: This study focuses on what portion of risk of pregnancy loss 20-28 weeks' gestation is associated with exposures amenable to public health campaigns/antenatal care adaptation. A case-control study of non-anomalous singleton baby loss (via miscarriage, stillbirth or early neonatal death) 20+0 to 27+6 (n=316) and randomly selected control pregnancies (2:1 ratio; n=632) at group-matched gestations will be conducted. Data is collected via participant recall (researcher-administered questionnaire) and extraction from contemporaneous medical records. Unadjusted/confounder-adjusted ORs will be calculated. Exposures associated with early stillbirth at OR≥1.5 will be detectable (p<0.05, ß>0.80) assuming exposure prevalence of 30%-60%. ETHICS AND DISSEMINATION: NHS research ethical approval has been obtained from the London-Seasonal research ethics committee (23/LO/0622). The results will be presented at international conferences and published in peer-reviewed open-access journals. Information from this study will enable development of antenatal care and education for healthcare professionals and pregnant people to reduce risk of early stillbirth. TRIAL REGISTRATION NUMBER: NCT06005272.

Childbirth Acquired Perineal Trauma study (CHAPTER): a UK prospective cohort study protocol.

INTRODUCTION: Childbirth-related perineal trauma (CRPT) is the most common complication of childbirth affecting 80% of women overall after vaginal birth. There remains a lack of comprehensive evidence relating to the prevalence of subsequent health problems. Current evidence is related to short-term outcomes, for example, pain, but there is less known about longer-term outcomes such as infection, wound dehiscence, pelvic floor function and psychological outcomes. This is a protocol for a cohort study assessing outcomes of women after CRPT. METHODS AND ANALYSIS: A multicentre, prospective UK cohort study aiming to include 1000 women. All women who have sustained CRPT will be eligible for inclusion and will be followed-up for 12 months after childbirth. The primary outcome will be perineal infection at 6 weeks post-birth. Secondary outcomes will include antibiotic use for perineal infection, wound breakdown, use of analgesia, the requirement for admission or surgical intervention, urinary and faecal incontinence, anxiety and depressive symptoms, sexual function and impact on daily activities. Outcomes will be measured at 6 weeks, 6 months and 12 months post partum, with some outcomes being measured at all time points and others at selected most appropriate time points only. Outcome data will be obtained from a review of clinical notes and from patient questionnaires. Simple descriptive statistics will be used to summarise characteristics and outcomes, with categorical variables expressed as percentages and continuous variables as mean averages, alongside the corresponding standard deviatons. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Research Ethics Council with reference 23/WA/0169. Data collected from the Childbirth Acquired Perineal Trauma (CHAPTER) cohort study will highlight the prevalence and type of complications after CRPT and which women are more at risk. After the conclusion of this study, findings will be used to work with governmental organisations and Royal Colleges to target resources and ultimately improve care.

Pregnancy outcomes in women following the Ross procedure.

INTRODUCTION: The Ross procedure, where a pulmonary autograft (neoaorta) replaces the aortic valve, has excellent long-term outcomes in patients with congenital aortic valve disease. However, there are reports of neoaortic dilatation and dissection. An increasing number of women are wishing to become pregnant following the Ross procedure, but little is known about the occurrence and risks of neoaortic dilatation and complications in pregnancy. We investigated neoaorta function and outcomes in pregnancy following the Ross procedure. METHODS: This retrospective study investigated women post-Ross procedure at a tertiary ACHD unit between 1997 and 2021. Imaging evaluated neoaortic root dimensions and regurgitation pre-, and post- pregnancy, compared with matched non-pregnant controls. Primary endpoints were change in neoaortic dimensions, degree of regurgitation and adverse maternal outcomes. RESULTS: Nineteen pregnancies in 12 women were included. The mean change in neoaortic root diameter post-pregnancy was 1.8 mm (SD 3.4) (p = 0.017). There was no significant change in neoaortic dimensions in matched controls during follow-up. There were no cases of dissection, arrhythmia, acute coronary syndrome, or maternal mortality. Three deliveries were pre-term, including one emergency Caesarean section due to maternal cardiac decompensation, requiring aortic root replacement post-partum but there were no neonatal deaths. CONCLUSIONS: Pregnancy following the Ross procedure is associated with neoaortic dilatation, and pregnancy is generally well tolerated. Although adverse maternal outcomes are uncommon, there are still rare cases of cardiac complications in and around the time of pregnancy. These findings emphasise the need for accessible pre-pregnancy counselling, risk stratification and careful surveillance through pregnancy by specialist cardio-obstetric multi-disciplinary teams.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Prenatal diagnosis of isolated right pulmonary agenesis using sonography alone: case study and systematic literature review.

Pulmonary agenesis is a rare congenital anomaly, estimated to complicate around 1 per 15,000 pregnancies, in which there is complete absence or severe hypoplasia of one or both lungs, frequently associated with other abnormalities. A prospective prenatal diagnosis is a challenge, and a substantial proportion of cases are diagnosed by fetal magnetic resonance imaging, postnatal computed tomography, or postmortem. Thus, there are only a few reported cases of prenatal diagnosis in the literature. We report the prenatal diagnosis of isolated right lung agenesis diagnosed with sonography alone at a relatively early gestational age. We also present a systematic review of the literature for this condition to accompany this case study.

Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section.

Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non-pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non-pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

The quality of reporting of primary test accuracy studies in obstetrics and gynaecology: application of the STARD criteria.

BACKGROUND: In obstetrics and gynaecology there has been a rapid growth in the development of new tests and primary studies of their accuracy. It is imperative that such studies are reported with transparency allowing the detection of any potential bias that may invalidate the results. The objective of this study was to determine the quality of reporting in diagnostic test accuracy studies in obstetrics and gynaecology using the Standards for Reporting of Diagnostic Accuracy--STARD checklist. METHODS: The included studies of ten systematic reviews were assessed for compliance with each of the reporting criteria. Using appropriate statistical tests we investigated whether there was an improvement in reporting quality since the introduction of the STARD checklist, whether a correlation existed between study sample size, country of origin of study and reporting quality. RESULTS: A total of 300 studies were included (195 for obstetrics, 105 for gynaecology). The overall reporting quality of included studies to the STARD criteria was poor. Obstetric studies reported adequately > 50% of the time for 62.1% (18/29) of the items while gynaecologic studies did the same 51.7% (15/29). There was a greater mean compliance with STARD criteria in the included obstetric studies than the gynaecological (p < 0.0001). There was a positive correlation, in both obstetrics (p < 0.0001) and gynaecology (p = 0.0123), between study sample size and reporting quality. No correlation between geographical area of publication and compliance with the reporting criteria could be demonstrated. CONCLUSIONS: The reporting quality of papers in obstetrics and gynaecology is improving. This may be due to initiatives such as the STARD checklist as well as historical progress in awareness among authors of the need to accurately report studies. There is however considerable scope for further improvement.