Hepatocellular carcinoma in pregnancy: A systematic review.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy. MATERIAL AND METHODS: We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584). RESULTS: We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%). CONCLUSIONS: Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.

Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.

Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.822-5C>T) or compound heterozygous (c.[863dup];[1063G>A]) and (c.[521G>T];[890T>G]) variants in LFNG. Notably, the c.822-5C>T change, affecting the polypyrimidine tract of intron 5, is the first non-coding variant reported in LFNG. This study further refines the clinical and molecular features of spondylocostal dysostosis 3 and adds to the numerous investigations supporting the usefulness of trio-ES approach in prenatal and neonatal settings.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

An update of diagnostic efficacy of ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders.

PURPOSE OF REVIEW: Systematic screening and diagnosis of placenta accreta spectrum disorder (PAS) either by ultrasound or magnetic resonance imaging (MRI) would allow referral of high-risk women to specialized multidisciplinary teams. We aimed to report recent findings regarding the diagnostic accuracy of ultrasound and magnetic resonance imaging in the diagnosis of PAS. RECENT FINDINGS: Recent evidence from the literature shows that both ultrasound and MRI are good tests to identify PAS in high-risk populations. Ultrasound can also be used safely to guide management decisions, concentrating greater resources in patients with the higher risk of clinically significant PAS requiring complex peripartum management. Moreover, there are increasing data showing that routine contingent screening for PAS disorders based on the finding of a placenta implanted low in the uterine cavity and previous uterine surgery is effective in a public healthcare setting. A contingent screening strategy for PAS is feasible if placental location is routinely assessed during routine scans, and may even start from the first trimester of pregnancy. SUMMARY: Ultrasound is an effective tool to screen pregnancies at high risk of PAS. In such pregnancies, ultrasound and MRI are effective imaging modalities for guiding management.

Ultrasound and MRI appearance of abnormally adherent placenta in a woman with Asherman's syndrome.

Although 10% of pregnancies following treatment of Asherman's syndrome are estimated to have abnormal placental adhesion, there is a paucity of reports describing imaging features in such cases. We describe ultrasound and MRI features in one of such cases, showing a peculiar pattern of shallow but diffuse abnormally adherent placenta.

Timing of intra-fetal laser therapy for twin reversed arterial perfusion (TRAP) sequence: Retrospective series and systematic review and meta-analysis.

OBJECTIVE: To estimate the neonatal survival rate after intra-fetal laser (IFL) treatment for twin reversed arterial perfusion (TRAP) sequence, and to investigate the effect of gestational age at the time of procedure. METHODS: Retrospective cohort study of TRAP sequences followed at our institution from 2013-2020. Systematic review and meta-analysis of the neonatal survival rate after IFL was conducted. Both diamniotic and monoamniotic monochorionic pregnancies were included. A subgroup analysis to compare outcomes according to gestational age at procedure (<16+0 weeks or ≥16+0 weeks) was planned. RESULTS: Thirteen pregnancies were followed at our center and seven were treated with IFL: the survival rate was 57%. Ten studies published between 2008 and 2020 for a total of 156 cases were included in the meta-analysis. The overall neonatal survival after IFL was 79% (95% CI 0.72-0.86, I2 22%). A random-effects model comparing neonatal survival for IFL performed <16+0 weeks versus ≥16+0 weeks showed no significant difference between the two groups (OR = 0.93; 95% CI 0.37-2.33). CONCLUSION: IFL is a safe and minimally invasive technique for the treatment of TRAP sequence, with a survival rate of 79%. Gestational age at treatment (before or after 16 weeks) does not seem to affect neonatal survival rate.

Fetoscopic laser ablation therapy in monochorionic diamniotic twin pregnancies with twin-to-twin transfusion syndrome treated at a single centre over 10 years: a retrospective study.

OBJECTIVES: To review experience with fetoscopic laser ablation of placental anastomoses to treat monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) in a single centre over a ten-year period. METHODS: A retrospective study on 142 MCDA twin pregnancies complicates by TTTS treated with equatorial laser ablation of placental anastomoses (2008-2018). Solomon technique was also applied after 2013. Survival rates, neonatal outcome, intraoperative and post-laser complications were recorded, and prognostic factors analysed. RESULTS: A total of 133 cases were included in the final analysis; 41 patients were at stage II (30.8%), 73 were at stage III (62.9%), while only 12 (9%) at stage I and two patients (1.7%) at stage IV. Solomon technique was applied in 39 cases (29.3%). Survival of both twins was 51.1% (68/133), of a single twin 20.3% (27/133), and of at least one 71.5% (95/133), with an overall survival of 61.3% (163/266). TAPS and recurrent TTTS occurred in 8 (6%) and 15 (11.3%) patients. Survival of both fetuses increased over time (44.6 vs. 57.3%). A posterior placenta (p<0.003) and the use of the Solomon technique (p<0.02) were more frequent in cases with survival of both fetuses, while TTTS recurrence was significantly associated to the loss of one or two fetuses (p<0.01). Such associations were confirmed at logistic regression analysis. CONCLUSIONS: Survival of both twins can improve over time and seems to be favourably associated with a placenta in the posterior location and the use of the Solomon technique.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. 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. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

Opportunistic salpingectomy during postpartum contraception procedures at elective and unscheduled cesarean delivery.

OBJECTIVE: To compare intra- and postoperative surgical complications of opportunistic bilateral total salpingectomy during postpartum permanent contraception procedures in elective and unscheduled cesarean delivery. STUDY DESIGN: We conducted a retrospective cohort study (2010-2017) of women who had postpartum permanent contraception procedures during cesarean delivery, and we collected baseline characteristics, scheduling of delivery (elective versus unscheduled), operative time, estimated blood loss (EBL) and surgical complications (bleeding, iatrogenic injury, infection, anemia and relaparotomy). We classified patients according to contraceptive technique: bilateral total salpingectomy, bilateral partial salpingectomy with or without fimbriae, and other methods. RESULTS: Five hundred twenty-eight women underwent postpartum permanent contraception procedures, 245 (46.4%) had bilateral total salpingectomy, 239 (45.3%) had bilateral partial salpingectomy, and 48 (8.3%) underwent other methods. We did not find differences in baseline characteristics, operative time and EBL among postpartum permanent contraception groups. Unscheduled cesarean delivery did not influence the choice of postpartum permanent contraception technique (p=.22). Postpartum permanent contraception-related intraoperative bleeding occurred in 1 (0.4%) and 2 (0.9%) patients, respectively, in bilateral total and partial salpingectomy group (p=.23). Postoperative complications were 13 (5.3%) and 6 (2.5%), respectively, in bilateral total and partial salpingectomy groups (p=.11). Subgroup analysis confirmed no differences for intra- and postoperative complications during unscheduled cesarean delivery. We noted a 4.3-min increase in operative time for total salpingectomy after multivariate analysis (p<.01). CONCLUSION: At maternal request for postpartum permanent contraception during cesarean delivery, bilateral total salpingectomy can be a safe and feasible method even in case of unscheduled cesarean delivery. IMPLICATIONS STATEMENT: Our results suggest that bilateral total salpingectomy during any cesarean delivery may be an acceptable choice for its higher contraceptive efficacy and risk-reduction effect for ovarian cancer, at the price of a small increase in operative time.

Fetal anemia: Diagnosis and management.

Fetal anemia has been known for many years as a dangerous complication of pregnancy. Its most common causes are maternal alloimmunization and parvovirus B19 infection, although it can be associated with many different pathological conditions including fetal aneuploidies, vascular tumors, and arteriovenous malformations of the fetus or placenta and inherited conditions such as alpha-thalassemia or genetic metabolic disorders. Doppler ultrasonographic assessment of the peak velocity of systolic blood flow in the middle cerebral artery for the diagnosis of fetal anemia and intravascular intrauterine transfusion for its treatment are the current practice standards. Live birth rates as high as 95% have been reported in recent years. The additional role of intravenous immunoglobulin therapy and the long-term consequences of the condition are the subjects of active ongoing research.

Etiology and Prognosis of Severe Ventriculomegaly Diagnosed at Late Gestation.

OBJECTIVES: We sought to assess the causes and outcomes of severe VM diagnosed de novo after 24 weeks of gestation where a mid-trimester anomaly scan was described as normal. METHODS: Multicenter retrospective study of five European fetal medicine centers. The inclusion criteria were normal anatomy at the mid-trimester scan, uni/bilateral finding of posterior ventricle measuring ≥ 15 mm after 24 weeks with neonatal and postnatal pediatric and/or neurological assessment data. RESULTS: Of 74 potentially eligible cases, 10 underwent termination, the outcome was missing in 19 cases and there was 1 neonatal death. Therefore, 44 formed the study cohort with a median gestation at diagnosis of 32 + 0 weeks (25 + 6 - 40 + 5). VM was unilateral in five cases. Agenesis of the corpus callosum (ACC) and grade III/IV intraventricular hemorrhage (IVH) accounted for 14 cases each. ACC was isolated in 9 fetuses. Obstructive abnormalities included 5 arachnoid and 1 cavum velum interpositum cyst. Four fetuses had an associated suspected or confirmed genetic condition, 2 congenital infections, 1 abnormal cortical development and the etiology was unknown in 3/44. Postnatal assessment at median 20 months (3 - 96) showed 22/44 (50 %) normal, 7 (16 %) mildly abnormal and 15 (34 %) severely abnormal neurodevelopmental outcomes. CONCLUSION: One half of babies with severe VM diagnosed after 24 weeks have normal infant outcome with ACC and IVH representing the most common causes. Etiology is the most important factor affecting the prognosis of fetuses with severe VM diagnosed at late gestation.

Endometriosis, endometrioma, and ART results: Current understanding and recommended practices.

Endometriosis and infertility are linked in a complex relationship, and a number of different pathogenetic mechanisms may associate the two. Endometriosis is diagnosed in 6-8% of women undergoing ART. Women with endometriosis appear to have similar ART outcomes compared to controls in terms of live birth rates, despite a lower oocyte quality. Laparoscopy should not be routinely performed before ART with the only aim to diagnose mild or moderate endometriosis, but if the latter is found, surgical removal can be considered, as it might improve pregnancy rates. In case of more severe forms of the disease (endometrioma and deep infiltrating endometriosis), the benefits of surgery before ART are uncertain and must be balanced against risks. Management decisions should be individualized based on patient choice, age, associated symptoms, and the risk of repeat surgery.

TRAP Sequence in Monochorionic/Monoamniotic (MC/MA) Discordant Twins: Two Cases Treated with Fetoscopic Laser Surgery.

INTRODUCTION: Ablation of the acardiac twin umbilical cord in the TRAP protects the normal donor twin. MATERIALS AND METHODS: Two case descriptions, one of interstitial laser photocoagulation and one of laser umbilical cord occlusion (L-UCO) of the acardiac twin in monochorionic monoamniotic pregnancies are reported. RESULTS: L-UCO in two pregnancies with TRAP syndrome in the second trimester resulted in intrauterine fetal death in both cases after 1 month. Case 1 had no detectable cause of fetal death. Case 2 had rupture of the amniotic sac causing anhydramnios and acute chorioamnionitis. A groove on the umbilical cord of the normal twin indicated a cord stricture due to cord entanglement. CONCLUSION: Our experience confirms that the best timing and optimal treatment of MC/MA twins complicated by TRAP sequence still remains a controversial clinical issue. Cord entanglement may continue be a potential clinical risk factor for adverse perinatal outcome even after ablation therapy.

Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis.

OBJECTIVE: The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2). METHOD: The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007-2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis. RESULTS: TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies. CONCLUSION: Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.

The effects of surgery for endometriosis on pregnancy outcomes following in vitro fertilization and embryo transfer: a systematic review and meta-analysis.

PURPOSE: To review the literature about the effect of endometriosis on in vitro-fertilization and embryo-transfer (IVF-ET). METHODS: A search in EMBASE, MEDLINE, ClinicalTrial.gov, reference lists from 2000 to 2013 was conducted. Inclusion criteria were: endometriosis confirmed with histologic examination, women undergoing IVF-ET, endometriosis treated or diagnosed by surgery. Women undergoing IVF-ET after surgical removal of endometriosic implants, or a surgical diagnosis of endometriosis without its removal, were compared to women without endometriosis. Main outcomes were clinical pregnancy and delivery rates. RESULTS: Thirteen studies were selected, including 980 women with endometriosis and 5934 controls. Clinical pregnancy rate was lower in women with endometriosis than in controls (OR 0.65; 95 % CI 0.44-0.96), but delivery rate was similar (OR 1.17; 95 % CI 0.69-1.98). When surgery was operative, clinical pregnancy rate after IVF-ET was lower in endometriosis than controls (OR 0.54; 95 % CI 0.34-0.85), but delivery rate was similar (OR 1.12; 95 % CI 0.60-2.07). When surgery was diagnostic, clinical pregnancy (OR 1.15; 95 % CI 0.46-2.84) and delivery rates (OR 1.65; 95 % CI 0.36-7.45) did not differ between the groups. Site of endometriosis was not related to IVF-ET outcomes. Clinical pregnancy rates were similar between stage I-II and controls (OR 0.99; 95 % CI 0.63-1.56) but lower in stage III-IV than controls (OR 0.45; 95 % CI 0.29-0.70), whereas delivery rate was not associated with stage. CONCLUSIONS: In the presence of endometriosis, the clinical pregnancy rate after IVF-ET is lower than in controls. The prognosis is better for mild endometriosis compared with more advanced stages. Even after surgical removal of endometriosis, IVF-ET results remain worse than in controls.

Fetal surgery: an overview.

In utero fetal surgery interventions are currently considered in selected cases of congenital diaphragmatic hernia, cystic pulmonary abnormalities, amniotic band sequence, selected congenital heart abnormalities, myelomeningocele, sacrococcygeal teratoma, obstructive uropathy, and complications of twin pregnancy. Randomized controlled trials have demonstrated an advantage for open fetal surgery of myelomeningocele and for fetoscopic selective laser coagulation of placental vessels in twin-to-twin transfusion syndrome. The evidence for other fetal surgery interventions, such as tracheal occlusion in congenital diaphragmatic hernia, excision of lung lesions, fetal balloon cardiac valvuloplasty, and vesicoamniotic shunting for obstructive uropathy, is more limited. Conditions amenable to intrauterine surgical treatment are rare; the mother may consider termination of pregnancy as an option for many of them; treatment can be lifesaving but in itself carries risks to both the infant (preterm premature rupture of the membranes, preterm delivery) and the mother. This makes conducting prospective or randomized trials difficult and explains the relative lack of good-quality evidence in this field. Moreover, there is scanty information on long-term outcomes. It is recommended that fetal surgery procedures be performed in centers with extensive facilities and expertise. The aims of this review were to describe the main fetal surgery procedures and their evidence-based results and to provide generalist obstetricians with an overview of current indications for fetal surgery.

Fetal abdominal wall defects.

The most common fetal abdominal wall defects are gastroschisis and omphalocele, both with a prevalence of about three in 10,000 births. Prenatal ultrasound has a high sensitivity for these abnormalities already at the time of the first-trimester nuchal scan. Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas omphalocele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases. Challenges in management of gastroschisis are related to the prevention of late intrauterine death, and the prediction and treatment of complex forms. With omphalocele, the main difficulty is the exclusion of associated conditions, not all diagnosed prenatally. An outline of the postnatal treatment of abdominal wall defects is given. Other rarer forms of abdominal wall defects are pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate anus, spina bifida complex, prune-belly syndrome, body stalk anomaly, and bladder and cloacal exstrophy; they deserve multidisciplinary counselling and management.

Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R.

Wave-shaped ribs were detected at prenatal ultrasound in a 20(+1) week female fetus. At birth, skeletal radiographs showed marked hypomineralization and suggested hypophosphatasia. However, elevated blood calcium and alkaline phosphatase excluded hypophosphatasia and raised the possibility of Jansen metaphyseal dysplasia. Molecular analysis of the PTH/PTHrP receptor gene (PTH1R) showed heterozygosity for a previously undescribed transversion variant (c.1373T>A), which predicts p.Ile458Lys. In vitro evaluation of wild type and mutant PTH/PTHrP receptors supported the pathogenic role of the p.Ile458Lys substitution, and confirmed the diagnosis of Jansen metaphyseal dysplasia. This disorder may present prenatally with wavy ribs and in the newborn with hypomineralization, and may therefore be confused with hypophosphatasia. The mottled metaphyseal lesions typically associated with this disease appear only in childhood.