Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. Immunolabeling experiments and transmission electron microscopy of the sciatic nerve from one of the affected individuals revealed a lack of myelin. Functional tests using affected individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein. This is consistent with previous studies reporting arthrogryposis in Lgi4-deficient mice due to peripheral hypomyelination. This study adds to the recent reports implicating defective axoglial function as a key cause of AMC.

Vascular limb occlusion in twin-twin transfusion syndrome (TTTS): case series and literature review.

OBJECTIVE: The purpose of this study was to evaluate the phenomenon of vascular ischemic limb necrosis in twin-twin transfusion syndrome (TTTS). STUDY DESIGN: This was a multicenter retrospective review of ischemic limb necrosis in patients with TTTS. RESULTS: Twenty cases of fetal ischemic limb necrosis in association with TTTS were identified from 10 fetal medicine centers. The recipient was affected in 19 cases, and the lower limb was affected in 17 cases. The extent of the damage correlated with TTTS severity. Eighty percent of limb defects (16/20) clearly were unrelated to laser treatment (3 cases untreated, 7 cases after amnioreduction, 6 cases present at time of laser). The recipient was relatively polycythemic in 5 of 7 cases in which neonatal or fetal hemoglobin/hematocrit levels were available. CONCLUSION: Ischemic limb necrosis is a rare complication of TTTS. The lesion is unrelated to therapy and may be the result of polycythemia, hypertension, and vasoconstriction.

Successful Laparoscopic Management of Non-communicating Rudimentary Horn Pregnancy.

Unicornuate uteri are a type of Mullerian duct anomaly and the majority present with rudimentary horns. Rudimentary horn pregnancies are extremely rare and have a high risk of rupture. A high index of suspicion is needed to diagnose them early and unfortunately, the majority of cases are undetected until the patient presents with a ruptured uterus. Early diagnosis and management will reduce morbidities and mortality for patients. We present a case of a 29 year old who had a routine ultrasound scan in the first trimester that raised an index of suspicion for a rudimentary horn pregnancy. An MRI scan was performed and supplemented the ultrasound findings. The patient underwent laparoscopic management, and the non-communicating rudimentary horn, the foetus, and the attached tube were excised. The patient had a smooth recovery and had no complications.  Due to the rarity of rudimentary horn pregnancies, a high index of suspicion is needed for a diagnosis. Timely detection and intervention are crucial to prevent complications. Ultrasound scans and MRIs can aid in the diagnosis. Traditional management involved laparotomy, but with surgical advancements, laparoscopic surgery can be utilized as a less invasive alternative.

Intrathoracic displacement of pleuroamniotic shunt after successful in utero treatment of fetal hydrops secondary to hydrothorax. Case report and review of the literature.

BACKGROUND: Primary fetal pleural effusion can be associated with high perinatal morbidity and mortality, especially when it is associated with the presence of fetal hydrops. Pleuroamniotic shunting results in effective drainage and lung expansion which prolong the pregnancy and improve neonatal survival. Intrathoracic displacement of the shunt is a rare but a known complication of shunt insertion and can cause some infant morbidity. We present a case of successful antenatal treatment of primary fetal pleural effusion complicated with intrathoracic displacement of the shunt without any fetal and long-term infant morbidity. CASE REPORT: Our case presented with severe bilateral fetal pleural effusion, causing fetal hydrops treated successfully by pleuroamniotic shunting at 25 weeks of gestation which was complicated by dislodgement of the shunt into the fetal chest documented by antenatal ultrasound at 30 weeks. There was no recurrence of fetal pleural effusion or other antenatal complication. After delivery there were no postnatal complications, so removal of the shunt was not considered, and clinical follow-up of the infant to the age of 12 months was uneventful. CONCLUSION: The complication of intrathoracic displacement of a pleuroamniotic shunt can be recognized antenatally by ultrasound. Since there are no postnatal pulmonary complications related to the presence of the shunt inside the infant chest, conservative management in these cases appears to be a safe approach.

Usefulness of a placental profile in high-risk pregnancies.

OBJECTIVE: Test the hypothesis that a placental function profile can reassure most high-risk women with normal test results yet accurately can identify a subset of women who are destined for major complications that will be attributable to placental disease. STUDY DESIGN: This was a prospective study of 212 high-risk pregnancies that used the placental profile (16- to 18-week maternal serum screening, 18- to 23-week uterine artery Doppler imaging, and placental morphologic condition). Odds ratios (95% CI) were derived for intrauterine fetal death (IUFD), preterm delivery at < 34 weeks of gestation, preeclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP) syndrome, small for gestational age delivery, and early-onset intrauterine growth restriction (IUGR); all normal test results (n =125) were compared with > or = 1 abnormal test results. RESULTS: The odds of the development of adverse outcomes were significantly less in women with all normal test results (preeclampsia/HELLP [odds ratio, 0.2; 95% CI, 0.1-0.4]), preterm delivery (odds ratio, 0.1; 95% CI, 0.06-0.3), small for gestational age delivery (odds ratio, 0.2; 95% CI, 0.09-0.3), early-onset IUGR (0), and IUFD (odds ratio, 0.05 [0.01-0.2]). Combining those women with two (n = 21) of 3 (n = 15) abnormal test results together predicted 14 of 19 severe IUGR and 15 of 22 IUFD cases. CONCLUSION: This placental function profile at 16-23 weeks of gestation can reassure women with normal test results by identifying a smaller subset of women who are at reduced risk of perinatal morbidity or death from severe IUGR.

Bupivacaine with meperidine versus bupivacaine with fentanyl for continuous epidural labor analgesia.

OBJECTIVE: To compare the efficacy of bupivacaine-meperidine and bupivacaine-fentanyl mixtures when continuously infused epidurally to relief the labor pain. METHODS: We performed this prospective double-blinded study at Jordan University Hospital, Amman, Jordan between October 2005 and April 2006. Sixty-seven American Society of Anesthesia physical status I parturients were randomly divided into 2 groups, Group M (n=34) received a continuous infusion of 1 mg/ml of bupivacaine mixed with 1 mg/ml meperidine, and Group F (n=33) received a continuous infusion of 1 mg/ml bupivacaine mixed with 2 micrometer/ml fentanyl. Efficacy of analgesia, degree of motor block, hemodynamic variability, incidence of nausea and vomiting, pruritus, sedation, and the neonatal outcome were all compared between the 2 groups. A p value <0.05 was considered to be significant. RESULTS: Highly effective analgesia was achieved in both groups with a similar incidence of motor block, sedation, pruritus, and neonatal outcome. The only significant difference was in the incidence of nausea and vomiting. Group M had 8 parturients with nausea, compared with only 2 parturients in Group F (p=0.003). CONCLUSION: Bupivacaine-meperidine in a continuous epidural infusion is as efficient as bupivacaine-fentanyl for pain relief during labor, but associated with a higher incidence of nausea and vomiting.

Second-trimester prediction of severe placental complications in women with combined elevations in alpha-fetoprotein and human chorionic gonadotrophin.

OBJECTIVE: The purpose of this study was to determine the ability of uterine artery Doppler and placental ultrasound to identify adverse clinical outcomes attributable to severe placental dysfunction in women with second-trimester unexplained elevated maternal serum screening of alpha-fetoprotein and human chorionic gonadotropin. STUDY DESIGN: Fifty singleton pregnancies with elevated alpha-fetoprotein (3.5 multiples of median [range 2.1 to 10.5]) and human chorionic gonadotropin (5.3 multiples of median [range 2.5 to 21.7]) and a normal fetal anatomical ultrasound were prospectively evaluated with placental ultrasound and uterine artery Doppler at referral between 19 and 23 weeks' gestation. RESULTS: Abnormalities in both placental ultrasound and uterine artery Doppler (n = 24) predicted preterm delivery less than 32 weeks from any cause (n = 24) (75% sensitivity, 75% positive predictive value; likelihood ratio positive 3.3 [1.6 to 6.8]), intrauterine fetal death (n = 12) (100% sensitivity, 50% positive predictive value; likelihood ratio positive 3.1 [2.0 to 5.0]), and intrauterine growth restriction with absent/reversed end-diastolic flow (n = 17) (sensitivity 94%, positive predictive value 67%, likelihood ratio positive 3.9 [2.0 to 6.2]) . Ischemic-thrombotic pathology was present in 88% of placentas examined (n = 32). CONCLUSION: Uterine artery Doppler and placental morphology identified most pregnancies with combined abnormal maternal serum screening destined to result in extremely premature delivery and/or perinatal death. Abnormal maternal serum screening reports could include a recommendation for placental ultrasound testing when no fetal explanation has been identified.

Impact of selective laser ablation of placental anastomoses on the cardiovascular pathology of the recipient twin in severe twin-twin transfusion syndrome.

OBJECTIVES: We investigated the impact of selective laser ablation on the cardiovascular pathology of the recipient twin in twin-twin transfusion syndrome. STUDY DESIGN: Fetal echocardiograms and medical records were reviewed from 22 pregnancies with severe twin-twin transfusion syndrome where echocardiography was performed before and after laser. RESULTS: Before laser, cardiomegaly associated with right and/or left ventricular hypertrophy without ventricular dilatation, was observed in most cases. Right ventricular and left ventricular systolic dysfunction (shortening fraction <28%) was present in 59% and 27%, respectively, and diastolic dysfunction (based on inflow and venous Dopplers) in 73%. Shortly after laser, biventricular systolic function improved significantly and diastolic function tended to improve (50%, P = .06). Functional pulmonary atresia, secondary to right ventricular systolic dysfunction, resolved in 2 of 2 cases at post-laser echocardiography. On serial assessment, diastolic function was normal in 7 of 10, hydrops regressed in 4 of 5, and neither progressive myocardial hypertrophy nor anatomical right ventricular outflow obstruction were found. CONCLUSIONS: Selective laser ablation in severe twin-twin transfusion syndrome acutely improves biventricular systolic function and tends to improve diastolic function in the recipient twin.

Elective non-removal of the placenta and prophylactic uterine artery embolization postpartum as a diagnostic imaging approach for the management of placenta percreta: a case report.

BACKGROUND: Placenta percreta, invasion of placental tissue through the uterine wall, is a rare but potentially fatal complication of pregnancy. Historically, the diagnosis was made at laparotomy, usually during Caesarean hysterectomy. CASE: We describe a case of placenta percreta, in which the placenta was allowed to remain fixed to the uterine wall. Antenatal ultrasound and magnetic resonance imaging techniques were used to establish the diagnosis and guide clinical management. Elective postoperative uterine artery embolization down balloon catheters was used to prevent postpartum hemorrhage and to promote involution and shedding of the placenta. After 6 months, the uterus had involuted to the nonpregnant state. CONCLUSION: New diagnostic imaging techniques may be used to guide conservative management of placenta percreta, thereby maintaining fertility and avoiding hemorrhage, blood transfusion, and hysterectomy.

Mutations in PYCR1 cause cutis laxa with progeroid features.

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.

Prenatal cardiovascular manifestations in the twin-to-twin transfusion syndrome recipients and the impact of therapeutic amnioreduction.

OBJECTIVE: We evaluated the cardiovascular pathologic condition in the recipient twin in twin-to-twin transfusion syndrome and the influence of amnioreduction. STUDY DESIGN: Fetal echocardiograms and medical records of 54 pregnancies that were complicated by twin-to-twin transfusion syndrome were reviewed. Recipient twin right and left ventricular wall thickness, diameters, systolic and diastolic function, valve regurgitation, and structural cardiac defects were assessed at examination and after amnioreduction. RESULTS: At examination (n = 28 pregnancies), cardiomegaly because of right ventricular and/or left ventricular hypertrophy was observed in 58% of recipient twins, and biventricular hypertrophy was observed in 33% of recipient twins, without ventricular dilation. Biventricular diastolic dysfunction was present in two thirds of recipient twins, and right ventricular systolic dysfunction and significant atrioventricular valve regurgitation was observed in one third of recipient twins. Serial assessment (n = 21 pregnancies) revealed progressive biventricular hypertrophy and right ventricular systolic and biventricular diastolic dysfunction in most recipient twins. Steeper progression of hypertrophy, diastolic dysfunction, and structural or functional right ventricular outflow disease (20% incidence) were associated with an increased perinatal mortality rate. CONCLUSION: In twin-to-twin transfusion syndrome, the recipient twin has progressive biventricular hypertrophy with predominant right ventricular systolic and biventricular diastolic dysfunction. Despite amnioreduction, the cardiovascular disease persists and even progresses in many recipient twins.

Fetal hepatic calcifications: prenatal diagnosis and outcome.

OBJECTIVE: The purpose of this study was to provide information on the causes and postnatal outcomes of fetal liver calcifications that were detected by ultrasound imaging. STUDY DESIGN: Cases with fetal liver calcifications that were encountered between 1992 and 2001 were evaluated. A detailed fetal ultrasound imaging for associated abnormalities, maternal STORCH (syphilis, cytomegalovirus, herpesvirus 1 and 2, rubella, and Toxoplasma ) analysis, parvovirus serologic condition, and parental cystic fibrosis mutations analysis were performed; amniocentesis was offered in all cases. All infants who were born alive were examined and followed up. RESULTS: Sixty-one pregnant women with fetal liver calcifications were identified. Forty of 61 patients had additional fetal abnormalities; 21 of 61 cases of fetal liver calcifications were isolated; 11/61 patients (18%) had abnormal karyotypes (trisomy 13, 4 patients; trisomy 21, 2 patients; trisomy 18, 1 patient; monosomy X (45,X), 1 patient; 4p-, 22q+, and 8p+, 1 patient). Ten of 11 patients with abnormal karyotypes had other abnormalities that were found on ultrasound imaging. Two patients had intrauterine infection, one patient had cytomegalovirus, and one patient had parvovirus B19 infection. Eighteen of 40 patients underwent pregnancy termination, one fetus died in utero, one newborn infant died, and two infants had neurologic sequelae. Of 21 patients with isolated liver calcifications, one fetus had parvovirus B19 infection and one infant had trisomy 21. The remainder of the infants each had a good outcome. CONCLUSION: Fetal liver calcifications are relatively common. Isolated cases have a good prognosis after aneuploidy and infection have been ruled out. However, additional major abnormalities present a risk for chromosomal abnormalities, mainly trisomy 13.

The fetal cardiovascular response to antenatal steroids in severe early-onset intrauterine growth restriction.

OBJECTIVE: Our aim was to study the hemodynamic effects of betamethasone on fetuses with intrauterine growth restriction (IUGR) with absent or reversed end-diastolic (ARED) umbilical artery flow. STUDY DESIGN: Color/pulsed Doppler waveforms were obtained before and after intramuscular injections of betamethasone in 19 consecutive fetuses with IUGR/ARED and 6 control fetuses. Peak velocities and pulsatility index (PI) values were obtained from the umbilical (UA) and middle cerebral (MCA) arteries and intrahepatic umbilical vein (UV). RESULTS: Ten ARED fetuses developed transient positive umbilical end-diastolic flow after steroids, whereas nine fetuses showed persistent ARED. The persistent ARED subgroup demonstrated increased UA and UV peak velocities after steroids, which may indicate fetal hypertension. Fetal death (n=2) and severe acidosis (n=2) were confined to the subgroup with persistent ARED. CONCLUSION: Preterm IUGR/ARED fetuses exhibit divergent cardiovascular responses to prenatal steroids. Intensive Doppler-based fetal monitoring may identify a subset of fetuses prone to decompensation after maternal steroid administration.