Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Comparison of Serial Amnioinfusion Strategies for Isolated Early-Onset Fetal Renal Anhydramnios.

INTRODUCTION: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. METHODS: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's χ2 or Fisher's exact tests for categorical variables and Student's t tests or Wilcoxon rank-sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. RESULTS: Eleven participants underwent 159 amnioinfusions (external pilot: 3 patients, 21 amnioinfusions; feasibility: 8 patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p = 0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p = 0.21), feasibility participants maintained amniotic fluid longer. CONCLUSION: Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

Management advances for congenital diaphragmatic hernia: integrating prenatal and postnatal perspectives.

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic.

BACKGROUND: We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. METHODS: We conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. RESULTS: At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6-86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (-13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1-89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (-3.0), p = 0.28] had declining scores. CONCLUSION: These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. LEVEL OF EVIDENCE: III.

The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

The genetic etiologies of bilateral renal agenesis.

OBJECTIVE: The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition. METHODS: A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex. RESULTS: We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes. CONCLUSION: Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA.

Maternal exposure to polyethylene micro- and nanoplastics impairs umbilical blood flow but not fetal growth in pregnant mice.

While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 106 ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.

Prediction of Preterm Birth with the Uterocervical Angle in Singleton Pregnancies Treated with a Cervical Pessary.

BACKGROUND: Cervical pessaries are an established therapy option for patients at risk for spontaneous preterm birth (sPTB). The uterocervical angle (UCA) remains a promising sPTB predictor. However, its clinical significance has yet to be described in patients treated with a pessary. METHODS: This study analyzed data of patients treated with a pessary because of cervical shortening in singleton pregnancies. The patients were divided into 2 groups according to transvaginal ultrasound findings: the funneling group (n = 68) and the no-funneling group (n = 42). Moreover, we analyzed patients within these prespecified groups according to the UCA < 95° and ≥ 95°. RESULTS: Delivery occurred significantly earlier in patients treated with a pessary and with a high UCA ≥ 95°(p = 0.006). The median gestational age at delivery in patients treated with a pessary and with no funneling and a UCA < 95° vs. ≥ 95° were 39.00 and 36.14 weeks, respectively (p = 0.005). In cases with funneling and a UCA < 95° vs. ≥ 95° the mean gestational age at delivery was 38.14 and 38.07 weeks respectively (p=1,00). There was a significant negative linear correlation between UCA and the gestational age at delivery in all patients (p = 0.04), which was even profound in the group without funneling (p = 0.0002). However, we found no significant correlation between cervical length and gestational age at delivery in all patients (p = 0.42) as well as in the group without funneling (p = 0.28). CONCLUSION: In spite of pessary treatment, patients with UCA ≥ 95° presented with a higher risk of sPTB compared to patients with UCA < 95°. This suggests that the UCA seems to be a better predictor of sPTB than the cervical length in patients receiving pessary treatment.

Precarious hope: Ethical considerations for offering experimental fetal therapies outside of research after initial studies in humans.

OBJECTIVE: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. METHOD: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. RESULTS: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. CONCLUSION: Considering these points may advance the interests of fetuses, future children, and their families.

Polystyrene micro- and nanoplastics cause placental dysfunction in mice†.

Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106 ng/L of 5 µm polystyrene microplastics or 106 ng/L of 50 nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls. Maternal exposure to both microplastics and nanoplastics resulted in evidence of placental dysfunction that was highly dependent on the particle size. The umbilical artery blood flow increased by 48% in the microplastic-exposed group and decreased by 25% in the nanoplastic-exposed group compared to controls (p < 0.05). The microplastic- and nanoplastic-exposed fetuses showed a significant decrease in the middle cerebral artery pulsatility index of 10% and 13%, respectively, compared to controls (p < 0.05), indicating vasodilation of the cerebral circulation, a fetal adaptation that is part of the brain sparing response to preserve oxygen delivery. Hemodynamic markers of placental dysfunction and fetal hypoxia were more pronounced in the group exposed to polystyrene nanoplastics, suggesting nanoplastic exposure during human pregnancy has the potential to disrupt fetal brain development, which in turn may cause suboptimal neurodevelopmental outcomes.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Maternal exposure to polystyrene nanoplastics alters fetal brain metabolism in mice.

INTRODUCTION: Plastics used in everyday materials accumulate as waste in the environment and degrade over time. The impacts of the resulting particulate micro- and nanoplastics on human health remain largely unknown. In pregnant mice, we recently demonstrated that exposure to nanoplastics throughout gestation and during lactation resulted in changes in brain structure detected on MRI. One possible explanation for this abnormal postnatal brain development is altered fetal brain metabolism. OBJECTIVES: To determine the effect of maternal exposure to nanoplastics on fetal brain metabolism. METHODS: Healthy pregnant CD-1 mice were exposed to 50 nm polystyrene nanoplastics at a concentration of 106 ng/L through drinking water during gestation. Fetal brain samples were collected at embryonic day 17.5 (n = 18-21 per group per sex) and snap-frozen in liquid nitrogen. Magic angle spinning nuclear magnetic resonance was used to determine metabolite profiles and their relative concentrations in the fetal brain. RESULTS: The relative concentrations of gamma-aminobutyric acid (GABA), creatine and glucose were found to decrease by 40%, 21% and 30% respectively following maternal nanoplastic exposure when compared to the controls (p < 0.05). The change in relative concentration of asparagine with nanoplastic exposure was dependent on fetal sex (p < 0.005). CONCLUSION: Maternal exposure to polystyrene nanoplastics caused abnormal fetal brain metabolism in mice. The present study demonstrates the potential impacts of nanoplastic exposure during fetal development and motivates further studies to evaluate the risk to human pregnancies.

Dichorionic diamniotic heterotopic twin gestation with cesarean section scar implantation and placenta increta.

Heterotopic cesarean scar pregnancy is an extremely rare form of pregnancy and is defined as an intrauterine pregnancy coexisting with an ectopic pregnancy implanted in the cesarean scar. Cesarean scar ectopic pregnancy can also be a precursor for placenta accreta spectrum, a potentially life-threatening condition in which the placenta is abnormally adherent to the uterine myometrium and possibly adjacent organs. Although cesarean scar ectopic pregnancies are rare, there has been an increase in their incidence due to the rise in cesarean deliveries. We present the case of a 35-year-old patient with a heterotopic pregnancy with ectopic implantation in a cesarean scar and associated placenta increta, as well as the radiologic evaluation of placenta accreta spectrum and subsequent management.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations.

BACKGROUND: Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. OBJECTIVE: This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. STUDY DESIGN: This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). RESULTS: There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. CONCLUSION: Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.

Potential higher risk of tethered spinal cord in children after prenatal surgery for myelomeningocele: A systematic review and meta-analysis.

INTRODUCTION: We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. MATERIAL AND METHODS: On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). CONCLUSION AND DISCUSSION: This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.

Hypertensive Disorders of Pregnancy and the Cardiovascular System: Causes, Consequences, Therapy, and Prevention.

Hypertensive disorders of pregnancy continue to be significant contributors to adverse perinatal outcome and maternal mortality, as well as inducing life-long cardiovascular health impacts that are proportional to the severity and frequency of pregnancy complications. The placenta is the interface between the mother and fetus and its failure to undergo vascular maturation in tandem with maternal cardiovascular adaptation by the end of the first trimester predisposes to hypertensive disorders and fetal growth restriction. While primary failure of trophoblastic invasion with incomplete maternal spiral artery remodeling has been considered central to the pathogenesis of preeclampsia, cardiovascular risk factors associated with abnormal first trimester maternal blood pressure and cardiovascular adaptation produce identical placental pathology leading to hypertensive pregnancy disorders. Outside pregnancy blood pressure treatment thresholds are identified with the goal to prevent immediate risks from severe hypertension >160/100 mm Hg and long-term health impacts that arise from elevated blood pressures as low as 120/80 mm Hg. Until recently, the trend for less aggressive blood pressure management during pregnancy was driven by fear of inducing placental malperfusion without a clear clinical benefit. However, placental perfusion is not dependent on maternal perfusion pressure during the first trimester and risk-appropriate blood pressure normalization may provide the opportunity to protect from the placental maldevelopment that predisposes to hypertensive disorders of pregnancy. Recent randomized trials set the stage for more aggressive risk-appropriate blood pressure management that may offer a greater potential for prevention for hypertensive disorders of pregnancy. KEY POINTS: · Optimal management of maternal blood pressure to prevent preeclampsia and its risks is undefined.. · Early gestational rheological damage to the intervillous space predisposes to preeclampsia and FGR.. · First trimester blood pressure management may need to aim for normotension to prevent preeclampsia..

The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia.

INTRODUCTION: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation. We describe the possible role of PCSK9 in lipid metabolism in all compartments of the parturient (maternal blood, placental tissue, and fetal blood) in pregnancies with and without preeclampsia. METHODS: This is an observational study examining PCSK9 levels in maternal sera, umbilical cord blood, and PCSK9 protein content in placental tissue in three different locations (maternal placental interface, fetal placental interface, and umbilical cord) in women with and without preeclampsia at >23 weeks gestation. RESULTS: 68 parturients with preeclampsia and 55 without preeclampsia were enrolled. Maternal serum LDL-c (116.6 ± 48.9 mg/dL vs 146.1 ± 47.1 mg/dL, p = 0.0045) and PCSK9 (83 [61.8127.6] ng/mL vs 105.3 [83.5142.9] ng/mL, p = 0.011) were also reduced in the preeclamptics versus controls. There were no differences in PCSK9 protein content between preeclamptics and controls at comparative placental interfaces. However, PCSK9 protein content increased between the preeclampsia maternal placental interface (1.87 ± 0.62) and the preeclampsia umbilical cord (2.67 ± 1.08, p = 0.0243). DISCUSSION: PCSK9 levels are lower in maternal sera in preeclampsia when compared to controls. Placental PCSK9 protein content in preeclampsia increases from the maternal interface to the umbilical cord; however, this is not seen in controls. This suggests a potential compensatory mechanism for PCSK9 which allows for higher circulating fetal LDL-c levels in preeclampsia.