[Analysis of clinical characteristics and risk factors of postoperative complications in infants with early-onset necrotizing enterocolitis after enterostomy].

Objective: To investigate the clinical characteristics of children with early-onset necrotizing enterocolitis (NEC) undergoing enterostomy and analyze the risk factors for postoperative complications. Methods: Retrospective analysis was conducted on the clinical data (perinatal conditions, clinical characteristics, clinical outcomes, etc.) of NEC patients who underwent enterostomy at Beijing Children's Hospital from May 2016 to May 2023. The patients were divided into two groups based on the age of onset: an early-onset enterostomy group (<14 days) and a late-onset enterostomy group (≥14 days). Furthermore, the children with NEC were categorized into complication group and non-complication group based on whether there were complications after enterostomy. The differences in clinical data between these groups were analyzed, and the clinical characteristics of children with early-onset NEC and enterostomy were summarized. Multivariate logistic regression model was employed to analyze the risk factors for postoperative complications in NEC children with enterostomy. Results: A total of 68 cases were enrolled, including 43 cases in the early-onset enterostomy group [26 males and 17 females, aged (6.5±3.0) days] and 25 cases in the late-onset enterostomy group [15 males and 10 females, aged (21.0±3.0) days]. There were 28 cases (17 males and 11 females), age [M (Q1, Q3)] 9 (5, 14) days in the complication group and 33 cases (22 males and 11 females), aged of 14 (6, 21) days in the non-complication group. Compared to the late-onset enterostomy group, the early-onset enterostomy group had significantly higher rates of intraventricular hemorrhage [30.2% (13/43) vs 8.0% (2/25)], hemodynamically significant patent ductus arteriosus [37.2% (16/43) vs 12.0% (3/25)], mechanical ventilation≥72 hours after birth [39.5% (17/43) vs 16.0% (4/25)], stage Ⅲ NEC [(69.8% (30/43) vs 40.0% (10/25)], extensive NEC [27.9% (12/43) vs 8.0% (2/25)], and short-term postoperative complications [56.8% (21/37) vs 29.2% (7/24)] (all P<0.05).Multivariate logistic regression model analysis revealed that residual length of proximal small intestine was a protective factor for postoperative complications after enterostomy in NEC infants (OR=0.764, 95%CI: 0.648-0.901, P=0.001), but stage Ⅲ NEC was a risk factor (OR=1.042, 95%CI: 1.004-5.585, P=0.017). Conclusions: The incidence of postoperative complications is high, and the prognosis is poor in children with early-onset NEC enterostomy. The residual length of proximal enterostomy is a protective factor for postoperative complications of NEC enterostomy, but stage Ⅲ NEC is a risk factor.

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.

Spontaneous massive fetomaternal hemorrhage: two case reports and a literature review of placental pathology.

BACKGROUND: Massive fetomaternal hemorrhage (FMH) is a rare event during pregnancy that may cause severe fetal anemia or death. CASE PRESENTATION: This paper reports two cases of fetomaternal hemorrhage with unexplained reasons. Both cases required emergency caesarean sections for non-reassuring fetal status and were treated with neonatal blood transfusion. Fetomaternal hemorrhage was confirmed via maternal Kleihauer-Betke test. CONCLUSION: We found parenchymal pallor, increased nucleated red blood cells (nRBCs), and syncytial knots (SKs) in the placentas, which are compatible with fetal anemia. Immunohistochemical staining indicated VEGF, CD34, and CD31 expression in the endothelial cells of the capillaries, characteristic of massive FMH placenta. This article also reviews the particular histopathological changes in FHM placenta according to the placental lesion classification system.

Association Between Obesity and Fetal Acidosis at Scheduled Cesarean Delivery.

OBJECTIVE: To evaluate whether patients with obesity who undergo scheduled cesarean delivery under neuraxial anesthesia are at increased risk for umbilical artery pH less than 7.1 and base deficit 12 mmol or greater. METHODS: We conducted a multicenter, retrospective cohort study of individuals who delivered a term, singleton, nonanomalous neonate at one of four academic medical centers in New York City from 2013 to 2019 by scheduled cesarean under neuraxial anesthesia for whom fetal cord blood gas results were available. The primary study outcome was rate of fetal acidosis , defined as umbilical artery pH less than 7.1. This was compared between patients with obesity (body mass index [BMI] 30 or higher) and those without obesity (BMI lower than 30). Base deficit 12 mmol or greater and a composite of fetal acidosis and base deficit 12 mmol or greater were also compared. Secondary outcomes included neonatal intensive care unit admission rate, 5-minute Apgar score less than 7, and neonatal morbidity. Associations between maternal BMI and study outcomes were assessed using multivariable logistic or linear regression and adjusted for age, race and ethnicity, insurance type, cesarean delivery order number, and neuraxial anesthesia type. RESULTS: Of the 6,264 individuals who met inclusion criteria during the study interval, 3,098 had obesity and 3,166 did not. The overall rate of umbilical artery cord pH less than 7.1 was 2.5%, and the overall rate of umbilical artery base deficit 12 mmol or greater was 1.5%. Patients with obesity were more likely to have umbilical artery cord pH less than 7.1 (adjusted odds ratio [aOR] 2.7, 95% CI 1.8-4.2) and umbilical artery base deficit 12 mmol or greater (aOR 3.2, 95% CI 1.9-5.3). This association was not significantly attenuated after additional adjustments for potential mediators, including maternal medical comorbidities. We found no differences in secondary outcomes between groups. CONCLUSION: Maternal obesity is associated with increased odds of arterial pH less than 7.1 and base deficit 12 mmol or greater at the time of scheduled cesarean delivery under neuraxial anesthesia.

Identification and management of fetal anemia due to hemolytic disease.

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. AREAS COVERED: This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. EXPERT OPINION: In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause.

Diabetic Embryopathies.

Diabetic embryopathy is defined as congenital anomalies that are linked to maternal diabetes. The association between diabetes and fetal, neonatal, and long-term complications is well-established. These complications include organ or structural maldevelopment, fetal growth abnormalities, and learning/psychiatric comorbidities. Recent studies have elucidated the pathophysiology behind these conditions and outlined new management approaches. Caudal regression syndrome, also known as sacral agenesis, is a well-known but less described complication of maternal diabetes. The purpose of this review is to summarize existing research on common neonatal morbidities in infants of mothers with diabetes with a focus on caudal regression syndrome and its long-term associations.

Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization.

OBJECTIVE: The prenatal course of a rare case with fetal anemia caused by maternal anti-c alloimmunization was reported. CASE REPORT: A 39-year-old female with anti-c and anti-E antibodies against red cells had previously experienced a stillbirth. At her present pregnancy, titers of maternal antibodies and fetal middle cerebral artery peak systolic velocity (MCA-PSV) were frequently monitored to investigate the severity of fetal hemolytic anemia. Rather than manifesting as an increase in MCA-PSV, the anemic fetus was delivered at 32 weeks and one day of gestation with a sole presentation: polyhydramnios. Neonatal hospitalization course were compatible with hemolytic anemia. The baby was discharged at 48 days of age. CONCLUSION: This case illustrated the complexities of dealing with maternal red cell alloimmunization during pregnancy and the limitations of noninvasive diagnostic modalities for detecting fetal anemia, and highlighted that obstetricians should refer all available clinical parameters in order to offer appropriate perinatal care.

Red blood cell transfusions post diagnosis of necrotizing enterocolitis and the deterioration of necrotizing enterocolitis in full-term and near-term infants: a propensity score adjustment retrospective cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of serious gastrointestinal inflammatory diseases in newborn infants, with a high morbidity and mortality. Red blood cell transfusion (RBCT) plays a controversial and doubtful role in the treatment of NEC. In present study, we aim to analyze the association between RBCT and the deterioration of NEC. METHODS: This was a retrospective cohort study of near-term and full-term infants with a confirmed diagnosis of Bell's stage II NEC between Jan 1, 2010 and Jan 31, 2020. The maternal and infant baseline characteristics, treatment information and laboratory test for each case were collected. The eligible subjects were divided into two groups based on receiving RBCT post NEC diagnosis or not. The propensity score was used to eliminate potential bias and baseline differences. A multivariate logistic regression model was used to adjust the propensity score and calculate the odds ratio (OR) and 95% confidential interval (CI) of RBCT for the deterioration of NEC. RESULTS: A total of 242 infants were included in this study, 60 infants had a history of RBCT post NEC diagnosis, and 40 infants deteriorated from Bell's stage II to stage III. By adjusting the propensity score, RBCT post NEC diagnosis was associated with an increased risk for NEC deteriorating from stage II to III (adjusted OR 6.06, 95%CI 2.94-12.50, P = 0.000). CONCLUSIONS: NEC infants who required RBCT post NEC diagnosis were more likely to deteriorate from stage II to III in full-term and near-term infants.

Extremely Rare Case of Fetal Anemia Due to Mitochondrial Disease Managed with Intrauterine Transfusion.

This report describes a rare case of fetal anemia, confirmed as a mitochondrial disease after birth, treated with intrauterine transfusion (IUT). Although mitochondrial diseases have been described in newborns, research on their prenatal features is lacking. A patient was referred to our institution at 32 gestational weeks owing to fetal hydrops. Fetal anemia was confirmed by cordocentesis. After IUT had been performed three times, the anemia and associated fetal hydrops showed improvement. However, after birth, the neonate had recurrent pancytopenia and lactic acidosis. He was eventually diagnosed with Pearson syndrome and died 2 months after birth. This is the first case report of fetal anemia associated with mitochondrial disease managed with IUT.

Prenatal diagnosis of a 46,XY karyotype female fetus with an SRY-associated gonadal dysgenesis, conceived through an intracytoplasmic sperm injection: a case report.

BACKGROUND: Permanent progression of paternal age and development of reproductive medicine lead to increase in number of children conceived with assisted reproductive techniques (ART). Although it is uncertain if ARTs have direct influence on offspring health, advanced paternal age, associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT), more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development, majority of which are associated with the SRY gene. CASE PRESENTATION: We report a case of a non-invasive prenatal testing and ultrasound sex discordance in a 46,XY karyotype female fetus with an SRY pathogenic variant, who was conceived through an intracytoplasmic sperm injection (ICSI) due to severe oligozoospermia of the father. Advanced mean age of ICSI patients is associated with risk of de novo mutations and monogenic disorders in the offspring. Additionally, ICSI patients have higher risk to harbour infertility-predisposing mutations, including mutations in the SRY gene. These familial and de novo genetic factors predispose ICSI-conceived children to congenital malformations and might negatively affect reproductive health of ICSI-patients' offspring. CONCLUSIONS: Oligozoospermic patients planning assisted reproduction are warranted to undergo genetic counselling and testing for possible inherited and mosaic mutations, and risk factors for de novo mutations.

Antenatal Three-Dimensional Printing for Ex Utero Intrapartum Treatment Procedures.

BACKGROUND: Prenatal ultrasonography allows for timely identification of fetal abnormalities that can have an effect on securing the neonatal airway at delivery. We illustrate the role of antenatal three-dimensional printing in cases with fetal airway obstruction. CASE: We present two cases that highlight the utility of a three-dimensional printing technique to aid in ex utero intrapartum treatment procedures during cesarean delivery. CONCLUSION: Three-dimensional printing plays a complementary role to standard imaging options in optimizing presurgical planning, prenatal parental counseling, personalized patient care, and education of the multidisciplinary team in cases of fetal congenital airway obstruction.

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

Etiology and Outcome of Isolated Fetal Ascites: A Systematic Review.

OBJECTIVE: To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops. DATA SOURCES: PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases were searched using the following keywords: "fetus" OR "foetal" OR "fetal" OR "foetus" AND "ascites" from inception to February 2020. The search was limited to the English language. METHODS OF STUDY SELECTION: A total of 1,983 articles were identified through the search strategy. All studies containing five or more cases of isolated fetal ascites were included. TABULATION, INTEGRATION, AND RESULTS: Eleven studies, involving 315 cases of isolated fetal ascites, were eligible for inclusion in this systematic review. All included studies were evaluated using the tool for evaluating the methodologic quality of case reports and case series described by Murad et al. Data were summarized using narrative review and descriptive statistics. Two-tailed Fisher exact P values calculated from hypergeometric distribution were used to compare outcome by etiology. CIs were calculated with Clopper-Pearson exact binomial interval. The etiologies of isolated fetal ascites are genitourinary (24%), gastrointestinal (20%), viral or bacterial infections (9%), cardiac (9%), genetic disorders not otherwise categorized (8%), chylous ascites (6%), metabolic storage disorders (3%), other structural disorders (4%), other causes (4%) and idiopathic (13%). Survival is most favorable for cases of isolated fetal ascites as a result of chylous (100%), idiopathic (90%), gastrointestinal (77%) and genitourinary (77%) etiologies. Survival is least favorable for fetuses with isolated fetal ascites as a result of structural disorders (25%), cardiac etiology (32%) and metabolic storage disorders (33.3%). When pregnancy terminations were excluded, survival rates were similar between fetuses diagnosed at or after 24 weeks of gestation compared with those diagnosed at less than 24 weeks (74% vs 61%, P=.06). Progression of fetal ascites to fetal hydrops occurred in 6.6% (95% CI 3.6-9.6%) (17/259) of cases when pregnancies that were terminated were excluded. CONCLUSION: Isolated fetal ascites has a diverse etiology. Outcome is related to the etiology of isolated fetal ascites. In the majority of cases, fetal ascites does not progress to fetal hydrops. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020213930.

[Characterization of children born to mothers with Graves' disease]. / Caracterización de recién nacidos hijos de madres portadoras de enfermedad de Graves.

INTRODUCTION: Neonatal hyperthyroidism is a disease that can cause mortality and sequelae. To date, there is no clinical series of cases that allows us to know the local reality of this condition. OBJECTIVE: to charac terize the children of mothers with Graves' disease (GD) from a clinical and biochemical point of view. SUBJECTS AND METHOD: A prospective follow-up of all newborns (NB) of mothers with history of GD was performed in two public hospitals in Santiago, during 5 years. Clinical and laboratory variables of mother-child pairs and thyroid-stimulating hormone receptor antibodies (TRAbs) le vels were analyzed looking for associations between these variables and the development of neonatal hyperthyroidism. RESULTS: Seventy-six mother-child pairs were included (0.2% of all deliveries). Five neonates (6.6%) presented biochemical hyperthyroidism, and 3 of them developed clinical disease and required treatment. All 5 NBs who developed hyperthyroidism had mothers with positive or indeterminate TRAbs. No child of TRAbs-negative mothers developed the disease. TRAbs could be determined in only 65% of the mothers and 72% of the NBs. There was a significant correlation bet ween maternal TRAbs titers (p < 0.03), neonatal TRAbs titers (p < 0.008), and neonatal TSH between days 2-6 (p < 0.006), with the subsequent development of hyperthyroidism. All cases of neonatal hyperthyroidism were transient. There was no mortality in our series. CONCLUSIONS: This is the first national case series of children of mothers with GD. Maternal and neonatal TRAbs and TSH between days 2-6 of life were predictors of neonatal hyperthyroidism.

The protective effects of neural stem cells and neural stem cells-conditioned medium against inflammation-induced prenatal brain injury.

Intrauterine inflammation affects fetal development of the nervous system and may cause prenatal brain injury in offspring. Previously, neural stem cells have been extensively used as a therapeutic choice for nervous system diseases. Recently, the therapeutic ability of conditioned medium, harvested from cultured stem cells, has captured the attention of researchers in the field. Our study aimed to compare the therapeutic effect of neural stem cells (NSCs) or NSC-conditioned medium (NSC-CM) after prenatal brain injury. The animal model was induced by intraperitoneal injection of lipopolysaccharide into the pregnant mice and NSCs or NSC-CM were transplanted into the lateral ventricle of embryos in treatment groups. Inflammation and apoptosis were evaluated postpartum in offspring via measuring the expression of NLRP3 gene and protein, the expression and the activity of caspase-3, and the expression of pro-inflammatory cytokines by real-time PCR, immunohistochemistry, western blotting, ELISA, and colorimetric assay kit. A rotarod test was performed for motor function evaluation. Data showed that although NSC-CM fought against the inflammation and apoptosis and improved the motor function, NSCs acted more efficiently. In conclusion, the results of our study contend that NSCs have a better therapeutic effect than CM in prenatal brain injury.

Placental pathology in women with HIV.

Recognizing the importance of placental features and their unique functions can provide insight into maternal health, the uterine environment during the course of pregnancy, birth outcomes and neonatal health. In the context of HIV and antiretroviral therapy (ART), there have been great strides in the prevention of mother to child transmission of HIV. However, there is still paucity of data on the impact of HIV/ART exposure on placental pathology and studies available only examine specific patterns of placental injury, further justifying the need for a more defined and comprehensive approach to the differential diagnoses of HIV/ART-exposed placentae. The purpose of this review is to consolidate findings from individual studies that have been reported on patterns of placental injury in the context of HIV/ART exposure. In both the pre- and post-ART eras HIV and/or ART has been associated with placental injury including maternal vascular malperfusion as well as acute and chronic inflammation. These patterns of injury are further associated with adverse birth outcomes including preterm birth and current evidence suggests an association between poor placental function and compromised fetal development. With the ever increasing number of pregnant women with HIV on ART, there is a compelling need for full incorporation of placental diagnoses into obstetric disease classification. It is also important to take into account key elements of maternal clinical history. Lastly, there is a need to standardize the reporting of placental pathology in order to glean additional insight into the elucidation of HIV/ART associated placental injury.

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment.

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother's hypothalamic-pituitary-adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring's stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.