Assessing the impact of pregnancy planning on obstetric and perinatal outcomes in women with pregestational diabetes mellitus.

AIMS: We investigated the role of pregnancy planning in improving glycemic control and its potential impact on the overall pregnancy outcomes, obstetric outcomes, and perinatal well-being in women with pregestational diabetes mellitus (PGDM). METHODS: A retrospective observational cohort study was conducted, including all pregnant women with PGDM treated in our center 2012 and 2018. RESULTS: Among 425 participants, 26.6 % had planned pregnancies. The lowest rate of pregnancy planning was observed in women with type 2 diabetes mellitus (6.5 %). Women with planned pregnancies had lower BMI. Both pregestational HbA1c levels (6.66 % vs. 7.61 %, p < 0.001) and HbA1c levels at the first prenatal visit (6.39 % vs. 7.24 %, p < 0.001) were significantly lower in the planned pregnancy group. These differences persisted until the end of pregnancy (6.09 % vs. 6.47 %, p = 0.006). Although better glycemic control was associated with a non-significant decrease in fetuses with birth weight over 4000 g (18.1 % vs. 22.1 %) and 4500 g (3.0 % vs. 4.2 %), we did not find significant effects on other morbidity events, maternal outcomes, or the cesarean section rate. CONCLUSIONS: Pregnancy planning in PGDM women improved glycemic control and HbA1c levels. Limited impact on obstetric and perinatal outcomes suggests scope for other focused interventions to optimize maternal and fetal health.

Long-Term Neurodevelopmental Outcome After Selective Fetoscopic Laser Therapy for Stage I Twin-Twin Transfusion Syndrome.

Twin-twin transfusion syndrome (TTTS) is a serious complication in monochorionic (MC) pregnancies. Fetoscopic laser surgery (FLS) is the primary treatment for advanced TTTS, but managing Quintero stage I TTTS is still controversial. We conducted an observational study evaluating the 2-year neurodevelopment of fetuses, which underwent FLS for stage I TTTS, compared with advanced TTTS and uncomplicated monochorionic diamniotic twins (MCDTs). The study included 156 children: 14 in stage I TTTS group, 28 in advanced TTTS group, and 114 in uncomplicated twin group. In stage I TTTS, 92.9% showed normal neurodevelopment, with no severe neurological impairments observed. These results were comparable with uncomplicated twins (92.1% normal neurodevelopment, P = .921, adjusted odds ratio [aOR] = 1.56, 95% confidence interval [CI] = 0.42-5.79; 1.8% severe impairment, P = .617). Advanced TTTS had a non-significant lower rate of normal neurodevelopment (89.3%, P = .710, aOR = 1.31, 95% CI = 0.12-14.87). In conclusion, FLS for stage I TTTS shows favorable long-term neurodevelopmental outcomes, similar to uncomplicated MC pregnancies.

Maternal and obstetric outcomes after Ex-Utero Intrapartum Treatment (EXIT): a single center experience.

BACKGROUND: The Ex-utero Intrapartum Treatment (EXIT) is a procedure developed to manage a range of fetal conditions, aiming to ensure the maintenance of neonatal airway and preserving the feto-placental circulation. Its goal is to enhance the neonatal ability to successfully transition and adapt to postnatal life, thereby reducing perinatal morbidity and mortality. However, EXIT has been associated with a high risk of maternal complications. This paper provides an overview of the indications and characteristics of the EXIT procedure, as well as the obstetric outcomes and maternal complications. METHODS: A retrospective analysis was conducted on a cohort of patients undergoing EXIT at our center between January 2007 and December 2022. Maternal outcomes, including demographic information, data related to the surgical procedure, surgical complications, and postoperative complications were analyzed. To assess the severity of the surgical complications, a modified Clavien-Dindo classification was used. Comparative analysis was performed by randomly selecting a sample from elective cesarean deliveries performed at our center. RESULTS: A total of 34 EXIT procedures were performed. According to the modified Clavien-Dindo classification, we observed no major complications, while minor maternal complications were present in 2.94% of cases. Compared to elective cesarean deliveries (n = 350), there were no significant differences in terms of maternal complications, highlighting the similarity observed in the mean decrease in postoperative hemoglobin (1.15 g/dL in EXIT vs. 1.2 g/dL in elective cesarean deliveries, p = 0.94). In EXIT group, there was a higher rate of polyhydramnios (26.47% vs 6.59%, p < 0.001), as well as the need for amnioreduction (14.71% vs 0%, p = 0.001) and preterm delivery (32.35% vs 6.02%, p = 0.001). There were no cases of endometritis, post-procedural fever, or abruptio placentae following EXIT. CONCLUSIONS: EXIT can be considered a safe procedure when performed under adequate conditions, including appropriate uterine access and proper anesthetic management. In our series, EXIT procedure was not associated with a higher incidence of maternal complications when compared to elective cesarean delivery. TRIAL REGISTRATION: Retrospectively registered.

Maternal and Neonatal Outcomes After Ex-Utero Intrapartum Treatment for Congenital Diaphragmatic Hernia: A Case Series.

INTRODUCTION: Despite advances in neonatal intensive care, fetuses with congenital diaphragmatic hernia (CDH) remain to have a poor prognosis. Exclusive postnatal treatment is inadequate in patients with moderate CDH (observed than expected lung-to-head ratio [O/E LHR] 26-45%) and can lead to respiratory failure at birth, requiring extracorporeal membrane oxygenation in 75% of cases. An ex-utero intrapartum treatment (EXIT) procedure may be beneficial in these cases, improving the fetal-neonatal transition. MATERIAL AND METHODS: We review all pregnancies with fetal isolated left CDH with moderate O/E LHR delivered by EXIT in our center from January 2007 to December 2022. Maternal and neonatal variables were analyzed. As primary outcomes, we included neonatal survival and mortality rates, surgical and infectious complications, uterine scar dehiscence, and blood loss during EXIT. As secondary outcomes, we studied recurrences of the diaphragmatic defect, long-term evolution, subsequent pregnancies, and mode of delivery. RESULTS: A total of 14 patients were delivered by the EXIT procedure, with a neonatal survival rate of 85.7%. All these children had optimal physical and neurocognitive development and no pulmonary morbidity. We found no major complications and 7.1% of minor maternal complications. There were no cases of surgical wound infection or endometritis. The median decrease in hemoglobin during the EXIT procedure was 1.9 mg/dL, and only one case required postoperative transfusion. Two out of the 14 women became pregnant again, and both pregnancies were uneventful. CONCLUSIONS: In our series, the EXIT procedure allows for adequate airway management associated with a high neonatal survival rate in patients with moderate O/E LHR CDH, with a low rate of neonatal and maternal complications.

Two Year Neurodevelopmental Outcome after Fetoscopic Laser Therapy for Twin-Twin Transfusion Syndrome: Comparison with Uncomplicated Monochorionic Diamniotic Twins.

BACKGROUND: Twin-twin Transfusion Syndrome (TTTS) represents a significant complication in monochorionic twin pregnancies, caused by an unbalanced shunting of blood through intertwin placental vascular anastomoses. Despite advances in fetoscopic laser surgery, TTTS is still associated with a high rate of cerebral injury. However, there are no studies comparing these pregnancies with uncomplicated monochorionic diamniotic (MCDA) twin pregnancies, establishing the baseline risk of neurodevelopmental impairment. The aim of this study is to evaluate the odds of neurodevelopmental impairment in MCDA twins who undergo fetoscopic laser surgery for twin-twin transfusion syndrome, in comparison to a cohort of uncomplicated MCDA twin pregnancies. STUDY DESIGN: This is a retrospective cohort study of children born from MCDA twin pregnancies at a single center between 2008 and 2019. A routine, standardized follow-up assessment was conducted at a minimum of 2 years after delivery. The primary outcome of this was a 2 year neurodevelopmental impairment. Neurological, motor, and cognitive development was assessed by using the revised Brunet-Lézine scale. RESULTS: 176 children met the enrolment criteria. Of these, 42 (24%; TTTS group) underwent fetoscopic laser surgery for TTTS during pregnancy, and 134 (76%; uncomplicated MCDA group) were uncomplicated MCDA pregnancies. The primary outcome was found in four children (9.52%) in the TTTS group and ten children (7.46%) in the uncomplicated MCDA group (p = 0.67, aOR 2.82, 95% CI 0.49-16.23). Major neurologic impairment was found in 2.38% after fetoscopic laser surgery and 1.49% in uncomplicated MCDA twins (p = 0.70, aOR 0.97, 95% CI 0.22-4.24). The data were adjusted by birth order, birth weight, and gestational age at birth. CONCLUSIONS: The outcome in MCDA twins who underwent fetoscopic laser surgery for TTTS is comparable to the outcome in uncomplicated MCDA twins. Our findings emphasize the need for long-term neurodevelopmental follow-ups in all children from monochorionic twin gestations.

Prenatal diagnosis of VACTERL association after early-first trimester SARS-COV-2 infection.

Organogenesis is a period of fetal development with a special vulnerability to biological and environmental agents. There are some viral infections whose transmission in the first trimester carries a significant risk for the development of congenital anomalies. Although the possibility of vertical transmission of SARS-CoV-2 during pregnancy has been demonstrated, there are no studies evaluating the impact of SARS-CoV-2 infection in the first trimester and its possible association with congenital anomalies. In this communication, we present the case of a pregnant woman with early SARS-CoV-2 infection, prenatally diagnosed with fetal VACTERL association by mid-trimester ultrasound. Further studies are needed to determine the causal association.

Mode of delivery, perinatal outcome and neurodevelopment in uncomplicated monochorionic diamniotic twins: a single-center retrospective cohort study.

BACKGROUND: There is no agreement on the effect of planned mode of delivery in the perinatal morbidity and neurodevelopment in uncomplicated monochorionic diamniotic as well as regarding the safest mode of delivery. In this paper we have aimed to analyze the impact of the mode of delivery in uncomplicated monochorionic diamniotic twins ≥ 32 weeks of gestation. MATERIAL AND METHODS: This study included 72 women, followed and attended at our department, with uncomplicated monochorionic diamniotic pregnancies who had a birth between 32.0 and 37.6 weeks of gestation from January 2012 to December 2018. Outcomes were recorded in women who underwent planned vaginal delivery (induced or spontaneous onset of labor), and women who underwent a planned cesarean section for any reason that excluded vaginal delivery. Primary outcomes included: (1) A composite of any of the following: neonatal death, 5-min Apgar score < 4, respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage, and necrotizing enterocolitis. (2) Neurodevelopmental status at 2 years of corrected age. RESULTS: In this period, 42 women (58.3%) had a planned vaginal delivery, and 30 women (41.7%) had a planned cesarean section. In the first group, 64.3% had a vaginal delivery. The rate of successful vaginal delivery was similar regardless the onset of labor. We did not find a higher composite perinatal morbidity in the planned vaginal delivery group (planned vaginal delivery: 3.6% vs. planned cesarean section: 8.3%, aOR 1.36, 95% CI 0.24-7.81). Considering the onset of labor, it was more frequent in the spontaneous subgroup (8.3% vs. 0%). The rate of neurodevelopmental impairment was higher in the planned cesarean section group, without reaching statistical significance [10.2% vs. 4.9%, aOR 1.53 (95% CI 0.37-6.29)]. CONCLUSIONS: In uncomplicated monochorionic diamniotic twins at ≥ 32 weeks of gestation, when the first twin is in vertex presentation, our results suggest that planned vaginal delivery is safe, with a successful outcome as well as high vaginal delivery rate.

Maternal effects induced by oral digoxin during treatment of fetal tachyarrhythmia: Case series and literature review.

OBJECTIVES: The aim of this study is to evaluate the prevalence of maternal complications derived from digoxin treatment and its relationship with digoxinemia, as well as its occurrence in relation to the different treatment doses and therapeutic schemes used. STUDY DESIGN: This is a retrospective observational study of women who received digoxin for the treatment of fetal tachyarrhythmia over a 10-year period at the University Hospital Virgen del Rocío (Seville). Data corresponding to the digoxin dose, its duration, serum digoxin levels and electrocardiographic parameters during follow-up were collected. Maternal side effects were reported, and its relationship to the treatment dose as well as digoxinemia. The study is accompanied by a narrative review of related literature. RESULTS: There were 10 cases eligible. During treatment, as least one symptom or sign was present in 30 % of cases, being in all cases digestive symptoms. In all those cases, the digoxin level was higher than established as therapeutic threshold (2 ng/mL), and all reversed within a maximum of 48 h after the dose decrease. Digoxinemia overdosing (> 2 ng/mL) was observed in 6 women (60 %), one of which reached the toxicity range (> 3 ng/mL). In all cases, normal range was achieved decreasing the dose of digoxin 0.25 mg every 24 h. No patient developed side effects with digoxinemia below 2 ng/mL. No electrocardiographic abnormalities appeared during treatment. CONCLUSION: Digoxin is a safe treatment for management of fetal tachyarrhythmias. Side effects appear frequently when serum digoxin level is over 2 ng/mL, but they are usually mild and self-limited. However, it remains advisable to monitor electrocardiographic changes and digoxinemia through the whole therapy to prevent serious complications related to digoxin toxicity.

Ex-Utero Intrapartum Treatment (EXIT): indications and outcome in fetal cervical and oropharyngeal masses.

BACKGROUND: The "Ex-Utero Intrapartum Treatment" (EXIT) procedure allows to ensure fetal airway before completion of delivery and umbilical cord clamping while keeping uteroplacental circulation. Airway obstruction in fetal oropharyngeal and cervical masses can be life-threatening at birth. In those situations, controlled access to fetal airway performed by a trained multidisciplinary team allows safe airway management, while feto-maternal circulation is preserved. We aim to review the indications and outcome of the EXIT procedure in a case series of fetal cervical and oropharyngeal masses. METHODS: We have carried out a retrospective review of all patients with fetal cervical and oropharyngeal masses who underwent an EXIT procedure between 2008 and 2019. Variables evaluated included indication for EXIT, ultrasound and MRI findings, the need of amnioreduction, gestational age at EXIT, birth weight, complications, operative time, survival rate, pathological findings, and postnatal evolution. Five patients are included in this series. One additional case has already been published. RESULTS: The diagnosis were cervical teratoma (n = 1), epulis (n = 1) and lymphangioma (n = 3). Polyhydramnios was present in 2 patients, requiring amnioreduction in one of them. Mean gestational age at EXIT was 36-37 weeks (range, 34-38 weeks). Median EXIT time in placental support was 9 min (range, 3-22 min). Access to airway was successfully established in EXIT in all cases. All children born by EXIT are currently healthy and without complications. CONCLUSION: The localization and characteristics of the mass, its relationship to the airway, and the presence of polyhydramnios seem to be major factors determining indications for EXIT and clinical outcome.

Searching the second hit in patients with inherited retinal dystrophies and monoallelic variants in ABCA4, USH2A and CEP290 by whole-gene targeted sequencing.

Inherited Retinal Dystrophies are clinically and genetically heterogeneous disorders affecting the photoreceptors. Although NGS has shown to be helpful for the molecular diagnosis of these conditions, some cases remain unsolved. Among these, several individuals harboured monoallelic variants in a recessive gene, suggesting that a comprehensive screening could improve the overall diagnosis. In order to assess the contribution of non-coding variations in a cohort of 29 patients, 25 of them with monoallelic mutations, we performed targeted NGS. The design comprised the entire genomic sequence of three genes (USH2A, ABCA4 and CEP290), the coding exons of 76 genes and two disease-associated intronic regions in OFD1 and PRPF31. As a result, likely causative mutations (8 novel) were identified in 17 probands (diagnostic rate: 58.62%), including two copy-number variations in USH2A (one deletion of exons 22-55 and one duplication of exons 46-47). Possibly damaging deep-intronic mutations were identified in one family, and another with a monoallelic variant harboured causal mutations in a different locus. In conclusion, due to the high prevalence of carriers of IRD mutations and the results obtained here, sequencing entire genes do not seem to be the approach of choice for detecting the second hit in IRD patients with monoallelic variants.

Resolution of maternal Mirror syndrome after succesful fetal intrauterine therapy: a case series.

BACKGROUND: Mirror syndrome (MS) is a rare obstetric condition usually defined as the development of maternal edema in association with fetal hydrops. The pathogenesis of MS remains unclear and may be misdiagnosed as pre-eclampsia. CASE PRESENTATION: We report a case series of MS in which fetal therapy (intrauterine blood transfusion and pleuroamniotic shunt) resulted in fetal as well as maternal favourable course with complete resolution of the condition in both mother and fetus. CONCLUSIONS: Our case series add new evidence to support that early diagnosis of MS followed by fetal therapy and clinical maternal support are critical for a good outcome.