Fetal Maturity Research Articles

МикроРНК: проблемы консервации в сцеженном грудном молоке

This review focuses on the issues of preservation of the qualitative characteristics of expressed breast milk with different methods of its conservation. The separation of a mother from her child hospitalized in the intensive care unit due to severe neonatal pathology fundamentally changes the pattern of interaction in the mother-child dyad. The realization of breastfeeding, which is optimal for a newborn, is often complicated by a complex set of medical and social problems. At the same time, providing a child with expressed breast milk while maintaining lactation is a technical burden that is imposed on the staff of medical institutions, particularly the neonatal intensive care and nursing units. Today, many neonatal institutions have organized breastfeeding units with breast milk jars, which solves this problem, but current research on the composition of breast milk poses new challenges to practitioners in preserving the quality of breast milk. Discoveries made in the last decade point to a more expanded structure and profound impact of breast milk on the growth, maturation, and formation of organs and structures of the newborn. MicroRNA is one of the important biologically active molecules. These molecules mediate the expression of about 60% of human genes. The results obtained in recent decades suggest a direct and indirect effect of microRNAs on the formation and maturation of fetus in intrauterine and extrauterine conditions through the mother-to-child information transmission by breast milk. The preservation of these molecules during the conservation of breast milk represents a significant task that implies a deeper understanding of the interaction in the mother-infant system. Key words: newborns, microRNA, microbiota, exovesicles, breast milk storage, breastfeeding, expressing milk, storage technologies

RETRACTED ARTICLE: Impacts of lipopolysaccharide on fetal lung developmental maturity and surfactant protein B and surfactant protein C protein expression in gestational diabetes mellitus rats

Statement of Retraction Yue Gao, Ziwei Zhang, Yan Wang, Dayong Zhou, Jinghua Zhou, Jinghua Zhang, Xiaoyu Chen, Xin Li, and Qingliang Shao- 2022, Impacts of Lipopolysaccharide on Fetal Lung Developmental Maturity and Surfactant Protein B and Surfactant Protein C Protein Expression in Gestational Diabetes Mellitus Rats, Bioengineered 13(1), doi: 10.1080/21655979.2021.2013099 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Successful Pregnancy Outcome after Amnioreduction Treated Acute Polyhydramnios Caused by Duodenal Atresia.

The aim of our manuscript is to report of a successful perinatal outcome after treatment of acute polyhydramnios caused by duodenal atresia. A 34-year-old G3P1 was referred due to polyhydramnios in the 30th week of pregnancy. Ultrasound revealed polyhydramnios, amniotic fluid index (AFI) 28, and a double bubble sign that indicated duodenal atresia and dilatated oesophagus. In the 32nd week of gestation, the volume of amniotic fluid increases, AFI 35, along with symptoms of dyspnea and abdominal pain. Due to the clinical picture and the early gestational age, it was decided to perform an amnioreduction. In the 36th week of gestation cesarean section was performed. The baby was taken for exploratory laparotomy and found to have a simultaneous complete duodenal atresia and annular pancreas with associated dilated the first portion of the duodenum and the stomach. A side-to-side duodenoduodenostomy via single-layer hand-sewn anastomosis was performed over a transanastamotic feeding tube (TAFT). The postoperative course was uneventful. Amnioreduction is useful and safe in the treatment of acute polyhydramnios caused by duodenal atresia and thus has a significant role in prolonging gestation until fetal maturity.

Effects of Ponderal Index on Neonatal Mortality and Morbidities in Extremely Premature Infants.

BackgroundTo evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes.MethodsWe selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270).ResultsThe mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively; P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants.ConclusionThe MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.

Meconium - Stained Amniotic Fluid in Labour – its Significance and Correlation to Early Maternal and Neonatal Outcome – A Prospective Case Control Study in A Tertiary Care Center

Background: Meconium-stained amniotic fluid (MSAF) is a well-known factor which associated with significant adverse pregnancy outcomes. Meconium Aspiration Syndrome (MAS) occurs in about 5% of deliveries with MSAF and death occurs in about 12% of infants with MAS. The significance of meconium claimed to be varied from being entirely physiological, which exhibits sign of fetal maturity, to a sign of fetal distress as a response to hypoxic insult to the foetus. This study was carried out in a tertiary care centre; with the aim of detecting the significance of MSAF. Additionally, this study compares the fetal and maternal outcome in deliveries complicated by meconium-stained amniotic fluid and critically evaluates the associated predisposing maternal and fetal factors for MSAF. Method: This prospective case-control study was carried out in Colombo South Teaching Hospital (University Professorial Obstetrics Unit), Sri Lanka. Women who presented to the unit with pre-defined selection protocol were recruited to the study until the sample size (n = 216 in each arm) is achieved. The Sample was categorized in to two groups depend on the presence or absence of Meconium-stained amniotic fluid. Mean, standard deviation, median and 95% confidence interval are computed for quantitative variables. Chi-square test is applied for calculating the statistical significance of variables such as grades of meconium and Apgar score at 95% confidence interval. The p-value &lt;0.05 and 95% confident interval was utilised to assess the statistical significance. Results: Presence of diabetes in current pregnancy was a significant risk factor for meconium-stained amniotic fluid at delivery with odd ratio of 2.397 (95% Confident Interval 1.203 - 3.568) and p value of &lt;0.00.1. There is a statistically significant association between the mode of delivery and the nature of meconium with odd ratio of 3.029 (95% Confident Interval 1.887 – 3.136) and p value &lt; 0.001, when its moderate to thick meconium staining. Presence of moderate to thick meconium increase the risk of neonatal respiratory morbidity with increased NICU admissions, which is both statistically and clinically significant with odd ratio of 2.412 (95% Confident Interval 1.674 - 3.199) and p value 0.005 when compared with thin meconium staining. Overall, there is a 2-fold rise in operative vaginal deliveries and EM-LSCS (Emergency Lower Segment Caesarean Section) in the presence of MSAF which accountable for 67.3% of the deliveries compared to 37.2% in the clear liquor group. The follow up of neonates at one month and three months of life, revealed no statistically significant concerns on the development of these babies in either arm of the study population. Conclusion: Presence of meconium-stained amniotic fluid is one of the common indications for caesarean delivery. Therefore, the results of this study may help to reduce the number caesarean sections carried out when the meconium is detected during labour. Presence of thin MSAF can be physiological following gut maturation of term foetuses, thus utilization of continuous electronic fetal monitoring can reliably cut down the caesarean section rates without adding numbers to the adverse perinatal outcomes. On the other hand, timely interventions upon detection of abnormal Cardiotocography (CTG), such as operative vaginal delivery or EM-LSCS, can significantly minimise these adverse neonatal outcomes. Abnormal CTG in a clinical background of moderate to thick meconium is more alarming, which warrant urgent interventions compared to the presence of thin / lightly stained meconium.

Fetal adrenal cortex function in pregnancy, complicated by maternal insulin-dependent diabetes mellitus

Fetal adrenal cortex glucocorticoid andfetal hypophysial adrenocorticotropic function in normal pregnancy and pregnancy, complicated with maternal insulin dependent diabetes mellitus were examined in the present study. Statistically significant feta l hypercortisolemia was observed in pregnancies, complicated by insulin-dependent diabetes mellitus. Correlations between vascular complications o f maternal insulin-dependent diabetes mellitus and fetal cortisol andACTG levels were revealed during the investigation. Severe vascular lesions o f maternal diabetes have been associated with delayed feta l lung maturity. Fetal pulmonary maturity was significantly associated with fe ta l cortisol levels.

Adnexal Torsion During the Second Trimester of Pregnancy: Mc Burney Incision and Management Strategy

A 33-year-old pregnant woman at 26 weeks gestation presented with abdominal pain in the right iliac fossa. She had a history of a left ovarian cyst. The current pregnancy was normal. The patient was apyretic. Laboratory testing revealed no inflammatory syndrome (leukocyte count of 10G/L and pro c reactive levels were 8 mg/L). In the absence of a diagnosis and given a non-contributory abdominal ultrasound, MRI was requested and revealed a right ovarian teratoma measuring 55 × 73 mm. A surgical exploration of the abdominal cavity (Mc Burney point) using tocolytic treatment with atosiban and after fetal maturation by intramuscular injection of betamethasone 12 mg was made. Pelvic exploration performed under general anesthesia found a right adnexal torsion. Anatomopathology found a 6 cm right ovarian cystic mature teratoma with no signs of malignancy. The rest of the pregnancy went smoothly. The patient gave birth at 39 SA + 4 days to a healthy boy weighing 3080 g

Effect of maternal hemoglobin and iron status on fetal hemoglobin, iron status, growth and maturity

Background: Iron deficiency anemia during pregnancy is a major health issue in India. However, the status of iron stores in infants born to iron depleted mothers remains controversial and inadequately investigated. The present study is therefore an attempt to understand whether maternal anemia and iron stores have any significant effect on iron status and growth of fetus.Methods: This is a prospective, cross-sectional, hospital based study conducted at Mata Chanan Devi Hosital, Janakpuri, New Delhi. Hemoglobin and iron profile of 100 newborns and their mothers were taken. Mothers were divided into anemic and non anemic group to see the effect of maternal anemia on fetus.Results: A total of 100 newborns and their mothers were analysed. Cord hemoglobin and iron profile was significantly reduced in anemic compared to non anemic group. Birth weight of newborn was significantly reduced only in moderately anemic group as compared to non anemic group but there was no difference seen in length and head circumference.Conclusions: Maternal serum ferritin levels should be measured for the diagnosis of occult iron deficiency in the fetus so that timely measures can be taken to prevent iron deficiency anemia in the newborn.

MATERNAL AND PERINATAL OUTCOMES WITH ANTENATAL CORTICOSTEROID ADMINISTRATION IN PRETERM DELIVERIES AT GOVERNMENT DISTRICT HOSPITAL, NANDYAL- AN OBSERVATIONAL STUDY

MATERNAL AND PERINATAL OUTCOMES WITH ANTENATAL CORTICOSTEROID ADMINISTRATION IN PRETERM DELIVERIES AT GOVERNMENT DISTRICT HOSPITAL, NANDYAL- AN OBSERVATIONAL STUDY

Life Course Impact of Glucocorticoids During Pregnancy on Muscle Development and Function.

Maternal stress, such as maternal obesity, can induce severe gestational disease and hormonal disorder which may disrupt fetal organ maturation and further cause endangered early or future health in offspring. During fetal development, glucocorticoids are essential for the maturation of organ systems. For instance, in clinical applications, glucocorticoids are commonly utilized to pregnant women with the risk of preterm delivery to reduce mortality of the newborns. However, exposure of excessive glucocorticoids at embryonic and fetal developmental stages can cause diseases such as cardiovascular disease and muscle atrophy in adulthood. Effects of excessive glucocorticoids on human health are well-recognized and extensively studied. Nonetheless, effects of these hormones on farm animal growth and development, particularly on prenatal muscle development, and postnatal growth, did not attract much attention until the last decade. Here, we provided a short review of the recent progress relating to the effect of glucocorticoids on prenatal skeletal muscle development and postnatal muscle growth as well as heart muscle development and cardiovascular disease during life course.

Comparison of fetal lung maturation in fetuses with intrauterine growth restriction with control group, using lung volume, lung/liver and lung/muscle signal intensity and apparent diffusion coefficient ratios on different magnetic resonance imaging sequences

Purpose To compare lung volume, lung apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) on different magnetic resonance imaging (MRI) sequences between intrauterine growth restriction (IUGR) fetuses and the control group. Materials and methods 49 IUGR and 58 non-IUGR fetuses were imaged using 3 Tesla MRI units. Total lung volume (TLV), lung/liver SIR (LLSIR) and lung/muscle SIR (LMSIR) in T1 and T2-weighted sequences and lung/liver ADC ratio (LLADCR) and lung/muscle ADC ratio (LMADCR) were assessed. Results LLSIR and LMSIR were significantly higher in the T1-weighted sequence (p-value: .03) and LLADCR and LMADCR were significantly lower on diffusion-weighted imaging (DWI) in IUGR fetuses compared to the control group (p-value: .01). There was no significant difference in SIRs in the T2-weighted sequence between the two groups. Although TLV was increased with gestational age in both groups, it was significantly lower in the IUGR group (mean: 82 ± 22.7 ml vs. 110.8 ± 18 ml, p-value: <.001). Conclusion The T1-weighted sequence and DWI seem to be better than the T2-weighted sequence for assessing the faint difference of lung maturity between groups. However, SIR differences were not as meaningful as TLV differences and this could be related to the complex maturation process in IUGR fetuses as the effect of higher endogenous corticosteroids.

Abstract 9810: Acute Exposure to Vaping E-Liquid Induces Multiple Cardiotoxic Effects on Fetal-Like Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Epicardial Cells

Introduction: Cardiomyocytes (CM) and epicardial (EPI) cells are key to orchestrating proper heart development. Vaping during pregnancy is rising, however, its implications on the prenatal heart are not fully understood. We exploited the immature phenotype of human induced pluripotent stem (iPS)-derived CM (iCM) and EPI (iEPI) cells to investigate the acute effect of e-cigarette liquid (e-liquid) on early cardiogenesis. Hypothesis: E-liquid exposure triggers dysfunction in fetal-like cardiac cells via distinct mechanisms. Methods: Human iCM and iEPI cultures were exposed to heated e-liquid for 20 minutes, twice daily, for 3 weeks; controls were performed in parallel. Video microscopy monitored morphological alterations and contractions. Immunostaining/flow cytometry of cell markers, Annexin V, EdU incorporation quantified protein expression, cell viability and proliferation, respectively. Mean fluorescence intensity measured reactive oxygen species (ROS). Wound healing assays assessed cell migration. Data reported as mean±SD (n=4/study). Results: Human iPSCs were differentiated into cTnT + iCM and Wt1 + iEPI cells with ≥83% purity. Addition of e-liquid progressively pruned the iCM syncytium, and slowed contractions in small regions from day 12. E-liquid treatment dysregulated HIF1α/p53 signaling in iCM relative to control. This enhanced apoptosis (49±5% vs. 21±6%) and disrupted G 1 /S cell cycle progression (5±1% vs. 15±3% in S-phase). Sustained elevation of ROS production by 35±7% led to ~20% decline in NKX2.5 + progenitors (p&lt;0.05 for all). E-liquid treatment also impaired iEPI motility (77±5% vs. 30±7% of open wound area), and reduced the proportion of iEPI-derived PFGFRβ + pericytes and αSMA + smooth muscle cells by ≥31% (p&lt;0.05 for all). This was attributed to N-cadherin repression and E-cadherin upregulation, which promoted defective epicardial epithelial-to-mesenchymal transition that affected vascular mural cell differentiation. Conclusions: Acute e-liquid exposure is detrimental to iCM and iEPI cell survival, behavior and fate trajectories. Our study suggests that long-term maternal vaping may compromise fetal cardiovascular integrity and maturation, heightening the risk of developing congenital heart disease.

Spontaneous labor curve based on a retrospective multi-center study in Japan.

AimIn Japan, the criteria of the latent and active phases of the first stage of labor have not been decided. The Japan Society of Obstetrics and Gynecology (JSOG) Perinatal Committee conducted a study to construct a spontaneous labor curve in order to determine the point of onset of the active phase.MethodsThe participants were women who had spontaneous deliveries at four health facilities in Japan between September 1, 2011, and September 31, 2019. Spontaneous delivery was defined as the spontaneous onset of labor at term (37 weeks, 0 days to 41 weeks, 6 days) with vaginal delivery of a mature fetus in a cephalic position without uterotonic agents or epidural analgesia. The time points for each “cm” of dilation were collected starting from the time of full dilation retrogradely. The relationship between time since labor onset and cervical dilation was expressed as a curve using a smoothing B‐spline.ResultsA total of 4215 primiparous and 5266 multiparous women were included in this study. The spontaneous labor curve showed that in both primiparous and multiparous women, labor progress was slow until 5 cm cervical dilation, accelerating between 5 and 6 cm dilation, and steadily progressed after 6 cm dilation.ConclusionWe propose that the active phase of the first stage of labor be defined as starting at 5 cm dilation of the cervix, and that it be divided into an acceleration phase (5–6 cm dilation) and a maximal phase (>6 cm dilation).

VP24.04: The delayed fetal neurological maturation in women with threatened preterm labour

VP24.04: The delayed fetal neurological maturation in women with threatened preterm labour

ANGIOVAC USE IN ENDOCARDITIS DURING PREGNANCY: A NOVEL APPROACH FOR RECURRENT DEBULKING OF TRICUSPID INFECTIVE VEGETATIONS IN A 27-YEAR-OLD WOMAN IN HER 22ND AND 26TH WEEKS OF PREGNANCY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Infective endocarditis (IE) during pregnancy is a rare and life-threatening disease with maternal and fetal mortality rates as high as 33% and 29%, respectively. Intravenous (IV) antibiotics with or without surgical modalities are mainstays of treatment. The use of AngioVac offers a less invasive procedure for the removal of thrombi and emboli in patients with contraindications to surgery. While its use has not yet been reported or approved in pregnancy, we present a case where AngioVac was used for debulking vegetations in a patient with tricuspid endocarditis during pregnancy. CASE PRESENTATION: A 27-year-old G2P1001 woman at 21-weeks-gestation with a history of IV drug use, untreated hepatitis C, and hypertension presented to the hospital with 3 weeks of worsening lower extremity edema, palpable purpura, dyspnea, leukocytosis, and fever. Diagnostic workup revealed methicillin-resistant Staphylococcus aureus bacteremia and transthoracic echocardiography showed severe tricuspid valve regurgitation with two vegetations of 2.4 x 1.2 cm and 1.4 x 0.7 cm. Although she met surgical criteria, she was a poor surgical candidate due to septic shock and multi-organ failure. Despite medical management, her symptoms persisted, and she developed pulmonary septic emboli, hemoptysis, and sacroiliitis. Alternatively, the patient was offered an AngioVac procedure at 22 weeks and subsequently at 26 weeks for decompensation with recurrence of valve vegetations. This allowed for nonoperative treatment of her endocarditis and delivery at 33 weeks via cesarean section for superimposed preeclampsia. Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. Newborn's weight was 2000 grams. DISCUSSION: In IE during pregnancy, surgical management is generally avoided due to maternal/fetal morbidity and mortality. Unfortunately, our patient failed medical therapy and surgery carried an unacceptable risk. Current guidelines do not address IE in pregnancy. This may be due to the low incidence or reporting bias. The use of AngioVac proved beneficial. The debulking of vegetations on two occasions reduced the bacterial inoculum, thereby enhancing antibiotic therapy, gaining time for fetal maturation, and allowing the patient to survive to successful delivery. AngioVac device has been described for the treatment of right-sided endocarditis with vegetations, mainly through case reports in experienced centers, but not in pregnancy. This case carried significant challenges and a multidisciplinary discussion and strategy were key in optimizing patient and fetal outcomes. CONCLUSIONS: AngioVac debulking of IE vegetations is a novel approach and was safely used in our pregnant patient. Multidisciplinary discussion and strategy are imperative in the management of IE during pregnancy. More data is needed to widely establish the use of AngioVac in pregnancy. REFERENCE #1: Luo L, Sun Q, Chen L, Ying D, Wu X, Chen Z. Survival of the fetus during maternal thoracotomy under cardiopulmonary bypass for infective endocarditis. J Obstet Gynaecol Res. 2017 Oct;43(10):1634-1638. REFERENCE #2: Divekar A, Scholz T, and Fernandez J. Novel percutaneous transcatheter intervention for refractory active endocarditis as a bridge to surgery-AngioVac aspiration system. Catheterization and Cardiovascular Interventions. 2013;81:1008–1012. REFERENCE #3: Anitha J, Gurley F, et al. Cardiopulmonary bypass during pregnancy. Ann Thorac Surg 2011;91:1191-1197. DISCLOSURES: No relevant relationships by Vira Ayzenbart, source=Web Response No relevant relationships by Sameh Aziz, source=Web Response No relevant relationships by Fernando Fuentes, source=Web Response No relevant relationships by Heather Fuentes, source=Web Response Consultant relationship with Angiodynamics Please note: 5/2020-present Added 04/26/2021 by Mark Joseph, source=Web Response, value=Consulting fee

Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes

The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In vivo, in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytes in vitro, was also downregulated in fetal hearts at E17.5, 24h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC-1α were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility. KEY POINTS: Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart. In fetal cardiomyocytes in culture, glucocorticoids promote mitochondrial fatty acid oxidation, suggesting they facilitate the perinatal switch from carbohydrates to fatty acids as the predominant energy substrate. Administration of a synthetic glucocorticoid in late pregnancy in mice downregulates the glucocorticoid receptor and interferes with the normal increase in genes involved in fatty acid metabolism in the heart. In a sheep model of preterm birth, antenatal corticosteroids (synthetic glucocorticoid) downregulates the glucocorticoid receptor and the gene encoding PGC-1α, a master regulator of energy metabolism. These experiments suggest that administration of antenatal corticosteroids in anticipation of preterm delivery may interfere with fetal heart maturation by downregulating the ability to respond to glucocorticoids.

Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth.

Cholesterol and fatty acids are essential lipids that are critical for membrane biosynthesis and fetal organ development. Cholesteryl esters (CE) are degraded by hormone-sensitive lipase (HSL) in the cytosol and by lysosomal acid lipase (LAL) in the lysosome. Impaired LAL or HSL activity causes rare pathologies in humans, with HSL deficiency presenting less severe clinical manifestations. The infantile form of LAL deficiency, a lysosomal lipid storage disorder, leads to premature death. However, the importance of defective lysosomal CE degradation and its consequences during early life are incompletely understood. We therefore investigated how defective CE catabolism affects fetus and infant maturation using Lal and Hsl knockout (-/-) mouse models. This study demonstrates that defective lysosomal but not neutral lipolysis alters placental and fetal cholesterol homeostasis and exhibits an initial disease pathology already in utero as Lal-/- fetuses accumulate hepatic lysosomal lipids. Immediately after birth, LAL deficiency exacerbates with massive hepatic lysosomal lipid accumulation, which continues to worsen into young adulthood. Our data highlight the crucial role of LAL during early development, with the first weeks after birth being critical for aggravating LAL deficiency.

Antenatal corticosteroids in COVID-19 perspective.

The aim of this manuscript is to discuss the practice of antenatal corticosteroids administration for fetal maturation in severe acute respiratory syndrome coronavirus 2 positive pregnant women. Recent high-quality evidence supports the use of dexamethasone in the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Randomized disease outcome data have identified an association between disease stage and treatment outcome. In contrast to patients with more severe forms who benefit from dexamethasone, patients with mild disease do not appear to improve and may even be harmed by this treatment. Therefore, indiscriminate usage of fluorinated corticosteroids for fetal maturation, regardless of disease trajectory, is unadvisable. Obstetrical care needs to be adjusted during the COVID-19 pandemic with careful attention paid to candidate selection and risk stratification.

Associations between maternal antenatal corticosteroid treatment and mental and behavioral disorders in children

Importance Maternal antenatal corticosteroid treatment is standard care to accelerate fetal maturation when birth before 34 weeks is imminent. Recently, expansion of the indications beyond 34 gestational weeks has been debated. However, data about long-term outcomes remain limited, especially among infants who after treatment exposure are born at term. Objective To study if antenatal corticosteroid treatment is associated with mental and behavioral disorders in children born at term (≥37 weeks 0 days’ gestation) and preterm ( Design, Setting, and Participants Population-based retrospective cohort study using nationwide registries of all singleton live births in Finland surviving until 1 year and a within-sibpair comparison among term siblings. Children were born between January 1, 2006, and December 31, 2017, and followed up until December 31, 2017. Exposures Maternal antenatal corticosteroid treatment. Main Outcomes and Measures Primary outcome was any childhood mental and behavioral disorder diagnosed in public specialized medical care settings. Results Of the 674 877 singleton children born in Finland during the study period, 670 097 were eligible for analysis. The median length of follow-up was 5.8 (interquartile-range, 3.1-8.7) years. Of the 14 868 (2.22%; 46.1% female) corticosteroid treatment–exposed children, 6730 (45.27%) were born at term and 8138 (54.74%) were born preterm; of the 655 229 (97.78%; 48.9% female) nonexposed children, 634 757 (96.88%) were born at term and 20 472 (3.12%) were born preterm. Among the 241 621 eligible term-born maternal sibpairs nested within this population, 4128 (1.71%) pairs were discordant for treatment exposure. Treatment exposure, compared with nonexposure, was significantly associated with higher risk of any mental and behavioral disorder in the entire cohort of children (12.01% vs 6.45%; absolute difference, 5.56% [95% CI, 5.04%-6.19%]; adjusted hazard ratio [HR], 1.33 [95% CI, 1.26-1.41]), in term-born children (8.89% vs 6.31%; absolute difference, 2.58% [95% CI, 1.92%-3.29%]; HR, 1.47 [95% CI, 1.36-1.69]), and when sibpairs discordant for treatment exposure were compared with sibpairs concordant for nonexposure (6.56% vs 4.17% for within-sibpair differences; absolute difference, 2.40% [95% CI, 1.67%-3.21%]; HR, 1.38 [95% CI, 1.21-1.58]). In preterm-born children, the cumulative incidence rate of any mental and behavioral disorder was also significantly higher for the treatment-exposed compared with the nonexposed children, but the HR was not significant (14.59% vs 10.71%; absolute difference, 3.38% [95% CI, 2.95%-4.87%]; HR, 1.00 [95% CI, 0.92-1.09]). Conclusions and Relevance In this population-based cohort study, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children. These findings may help inform decisions about maternal antenatal corticosteroid treatment.

Mapping Human Fetal Brain Maturation In Vivo Using Quantitative MRI.

On the basis of a single multidynamic multiecho sequence acquisition, SyMRI generates a variety of quantitative image data that can characterize tissue-specific properties. The aim of this retrospective study was to evaluate the feasibility of SyMRI for the qualitative and quantitative assessment of fetal brain maturation. In 52 fetuses, multidynamic multiecho sequence acquisitions were available. SyMRI was used to perform multidynamic multiecho-based postprocessing. Fetal brain maturity was scored qualitatively on the basis of SyMRI-generated MR imaging data. The results were compared with conventionally acquired T1-weighted/T2-weighted contrasts as a standard of reference. Myelin-related changes in T1-/T2-relaxation time/relaxation rate, proton density, and MR imaging signal intensity of the developing fetal brain stem were measured. A Pearson correlation analysis was used to detect correlations between the following: 1) the gestational age at MR imaging and the fetal brain maturity score, and 2) the gestational age at MR imaging and the quantitative measurements. SyMRI provided images of sufficient quality in 12/52 (23.08%) (range, 23 + 6-34 + 0) fetal multidynamic multiecho sequence acquisitions. The fetal brain maturity score positively correlated with gestational age at MR imaging (SyMRI: r = 0.915, P < .001/standard of reference: r = 0.966, P < .001). Myelination-related changes in the T2 relaxation time/T2 relaxation rate of the medulla oblongata significantly correlated with gestational age at MR imaging (T2-relaxation time: r = -0.739, P = .006/T2-relaxation rate: r = 0.790, P = .002). Fetal motion limits the applicability of multidynamic multiecho-based postprocessing. However, SyMRI-generated image data of sufficient quality enable the qualitative assessment of maturity-related changes of the fetal brain. In addition, quantitative T2 relaxation time/T2 relaxation rate mapping characterizes myelin-related changes of the brain stem prenatally. This approach, if successful, opens novel possibilities for the evaluation of structural and biochemical aspects of fetal brain maturation.