Fetal Lung Maturity Research Articles

CORTICOTERAPIA ANTENATAL TARDIA, RISCOS E BENEFÍCIOS MATERNOS E FETAIS: UMA REVISÃO DE LITERATURA

This article addressed late antenatal corticosteroid therapy, a treatment that has been adopted in pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation, and who are at high risk of premature birth. One of the main complications and causes of morbidity in late preterm neonates is respiratory distress syndromes, and corticosteroids can aid in fetal lung maturation, preventing and/or reducing complications of this nature. However, the use of these drugs in the late antenatal period can pose some risks to the well-being and health of the mother-baby binomial. Therefore, the general objective of this article was to analyze the literary evidence about the efficacy of late antenatal corticosteroid therapy, both for the fetus and the pregnant woman. The specific objectives were to understand how corticosteroids should be administered, and whether the benefits provided outweigh the potential risks of their use at this stage of pregnancy. A literature review on the topic was developed, including scientific articles published in the last five years (2019-2024). Data collection was carried out through PubMED. The results confirmed that late antenatal corticosteroid therapy is effective in reducing pulmonary complications and should be considered in cases of high risk of premature birth. The main risks are increased chances of maternal hyperglycemia and, consequently, fetal hypoglycemia. Some studies also point to psychological and neurocognitive problems for the baby in the future. However, it was concluded that the benefits brought by corticosteroids to lung maturity outweigh the potential maternal and fetal risks, but treatment should be carried out with caution, evaluating each case individually and monitoring the long-term repercussions.

Abstract 4117594: Fetal Synthetic Glucocorticoid (sGC) Exposure Results in Later Life Cardiac Dysfunction and Ventricular Remodeling in Male Baboon Offspring

The “theory of developmental origins of health and disease” posits that stress in critical developmental periods will program life-course health and may affect cardiovascular (CV) health. Mothers at risk for premature delivery receive synthetic glucocorticoids (sGC) to enhance fetal lung maturation and manage fetal respiratory distress, but sGC exposure is linked to long-term CV dysfunction in offspring. Four groups of male baboons were studied: sGC exposed in utero at middle age (sGC-MA, 13.8±0.2Y), older sGC exposed in utero (sGC-O, 17.1±0.4Y), middle age unexposed (CTR-MA, 13.5±0.6Y), and older, unexposed baboons (CTR-O, 17.4±0.4Y). Gated, breath-hold, cine cardiac magnetic resonance imaging was performed at 3 Tesla (Siemens TIM Trio) to assess left ventricular (LV) function and myocardial strain, analyzed using cvi42® software. Mitochondrial electron transport chain (ETC) complex activity was analyzed using LV tissue from sGC-O and CTR-O euthanized baboons. Protein quantification was used to measure mitochondrial function and RNA-seq assessed differential gene expression and gene ontology (GO) enrichment. Unpaired t-tests were used. Data are reported as mean ± SD. Stroke volume and ejection fraction were similar in the elderly groups (4 sGC-O, 8 CTR-O). However, higher end-systolic and end-diastolic sphericity indexes (SI) and shorter LV axis lengths indicated remodeling. Also, global longitudinal and radial strains were reduced (both p<0.04) in sGC-O vs. CTR-O. Reduced LV cardiac output (p=0.005) was found in 5 sGC-MA animals vs 4 sGC-O animals, but not in 5 CTR-MA vs 8 CTR-O. In sGC-MA vs sGC-O, but not CTR-MA vs CTR-O, significant increases in SI (p=0.001), radial strain (p=0.02), and longitudinal (p=0.03) strain were found, but LV axis length (p=0.03) was reduced. LV mitochondrial analysis in 4 sGC-O vs 4 CTR-O myocardial samples revealed 33.5% less ETC activity (p=0.002) and 19.8% less complex I expression (p=0.048) in sGC. LV RNA-seq identified 63 upregulated and 20 downregulated genes in the sGC-O samples. GO pathway enrichment included changes in heart contraction, wounding responses, and leukocyte regulation pathways. These findings indicate that fetal sGC exposure developmentally programs offspring with LV remodeling and long-term cardiac and gene expression changes in male baboons, the closest available experimental nonhuman primate species to man. Future studies on females will probe sexual dimorphism in developmental programming.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

Lamellar Body Count (LBC) in amniotic fluid for prediction of fetal lung maturity

Background: Neonatal respiratory distress syndrome (RDS) is a disorder due to pulmonary immaturity with a high mortality characterized by low levels of pulmonary surfactant. RDS is one of the important causes of mortality in neonates. Objective: The aim of the study is to determine the lamellar body count (LBC) cutoff value for foetal lung maturity and to evaluate the clinical usefulness of LBC in predicting the neonatal respiratory distress syndrome (RDS) and to find if the Measurement of LBC can replace the conventional Lecithin/Sphingomyelin ratio. Methods: This prospective observational study was performed on total 47 pregnant women divided as 19 patients with premature labor and 28 patients with healthy full-term singleton pregnancy as controls, with gestational age between 28 – 41 weeks at Ain Shams university maternity hospital in period between April 2014 and January 2015 with inclusion and exclusion criteria. Results: RDS was diagnosed in 20 neonates, two neonates in the 1st group (7.1%) While 18 neonates in 2nd (94.7%) showed development of RDS. Mean lamellar body count in newborns with RDS: 39,200 ± 12,438 with median 37,500 and p-value was <0.0001. ROC (receiver operator characteristics) curve showed that by using 51000/µL as a cut-off point for LBC it is a good predictor for fetal lung maturity with sensitivity 95% and specificity 96.3%. There is a direct relationship between the gestational age and the lamellar body count as the lamellar body count increases as long as the gestational age proceeds with a highly significant positive correlation (p value <0.0001). Conclusion: As evident from the current study, LBC count now replacing the conventional Lecithin/Sphingomyelin ratio because the test can be performed with equipment found in most clinical analysis laboratories and is reliable in predicting foetal lung maturity. This study suggests that LBC cutoff value of ≥51,000/µL can predict pulmonary maturity and reduce the risk of neonatal respiratory distress syndrome.

Comparative Study between the Accuracy of Transcerebellar Diameter versus Femur Length and Biparietal Diameter Measurements in Estimation of Gestational Age during Third Trimester

Abstract Background Knowledge of accurate gestational age is of great importance in obstetric practice. Pregnancy complications as low birth weight, preterm labor are very common in pregnancies with unknown and inaccurate estimated gestational age, gestational age estimation is essential for proper prenatal care and determining whether the fetal size is appropriate-for- gestational age. Moreover, it is essential for many prenatal interventions, such as fetal lung maturation, use of magnesium for neuroprophylaxis in preterm infants, induction of delivery and neonatal resuscitation. Optimal assessment requires good judgment by the obstetrician caring for the patient. Objective To compare the accuracy of transcerebellar diameter versus the current fetal biometrics including (femur length and biparietal diameter) in estimation of the gestational age during the third trimester according to last menstrual period. Patients and Methods The study was conducted in clinic of Obstetrics and Gynaecology Department- MUST University Hospital. This study included 120 pregnant females. They were divided equally into three equal groups each contained 40 patients; Group I: Biparietal diameter measured group, Group II: Femur Length measured group, and Group III: Transcerebellar measured group. Results The comparison in 1 week proved that the TCD gave correct assessment of gestational age in 107 patients (89.17%), the BPD gave correct assessment of gestational age in 73 patients (60.83%) and the FL gave correct assessment of gestational age in 97 patients (80.83%). Conclusion Transcerebellar diameter is the most accurate and reliable method for assessment of gestational age in third trimester followed by FL and the least accurate is the BPD.

Impact of Corticosteroid Administration on Fetal Doppler Metrics and Neonatal Outcomes: A Comprehensive Review

Abstract Antenatal corticosteroid therapy is a crucial intervention to improve neonatal outcomes in pregnancies at risk of preterm birth. Corticosteroids such as betamethasone and dexamethasone enhance fetal lung maturation and reduce morbidity and mortality. To assess the effects of these drugs, we conducted a systematic review adhering to PRISMA guidelines. Data were located through extensive searches of PubMed, MEDLINE, Cochrane Library, Scopus, and Web of Science, using keywords such as “antenatal corticosteroids,” “fetal Doppler,” and “neonatal outcomes,” and applying filters for human studies published between 2013 and 2024. Studies were selected based on inclusion criteria that prioritized original research articles, systematic reviews, and meta-analyses in English. Screening and eligibility assessments were performed by independent reviewers, with full-text articles. Data extraction involved recording study designs, sample sizes, corticosteroid regimens, Doppler metrics assessed, and neonatal outcomes observed. The extracted data were synthesized qualitatively through narrative methods and quantitatively using meta-analysis where applicable. The review found that corticosteroid administration leads to transient reductions in the resistance and pulsatility indices of key fetal vessels, reflecting improved placental and cerebral perfusion. These Doppler changes correlate with better neonatal outcomes, including reduced respiratory distress syndrome and enhanced neurodevelopmental results. Despite these promising findings, limitations such as small sample sizes and short follow-up periods were noted. Future research should focus on larger, multicenter trials and long-term outcome assessments. Clinicians are advised to incorporate serial Doppler monitoring in high-risk pregnancies to optimize maternal-fetal management and neonatal outcomes.

Autoimmune thrombocytopenia refractory to prednisone during pregnancy: A case report

Immune thrombocytopenic purpura is a rare autoimmune hemorrhagic pathology. It’s association with pregnancy is also rare. The management of immune thrombocytopenic purpura in pregnancy can be a challenge in limited resource setting. We report the prenatal monitoring and delivery management of a patient with a severe form of immune thrombocytopenic purpura that became resistant to prednisone. The diagnosis was made at the 28th week of amenorrhea during a previous pregnancy. During this new pregnancy, severe biological signs appeared at 7th week of amenorrhea despite prednisone therapy. Betamethasone administered for fetal lung maturation in the 3rd trimester of the pregnancy showed in the same time a platelet count rebound which improved maternal and perinatal prognosis. This case report aims to show the interest of Betamethasone in the management of refractory immune thrombocytopenic purpura in pregnancy as an alternative therapy to prednisone with low cost and helped to minimize heavy platelet transfusions and gamma globulin in the peripartum period. Keywords: Immune thrombocytopenic purpura, pregnancy, Betamethasone, Niger.

The Potential of Ambroxol as a Panacea for Neonatal Diseases: A Scoping Review.

Ambroxol, a commonly used mucolytic agent, has been extensively studied for its clinical effectiveness in managing respiratory conditions in pediatric and adult patients. The existing body of research on ambroxol demonstrates its safety and efficacy. However, its potential role in preventing and treating neonatal diseases still needs to be explored. This scoping review aims to shed light on the unexplored potential of ambroxol, particularly its applications in perinatal and neonatal care. We aim to offer valuable insights for healthcare professionals, researchers, and academics, thus presenting a positive perspective. Key scientific databases such as Google Scholar, PubMed, Cochrane Library, and Europe PMC were meticulously searched for relevant literature on ambroxol in perinatal and neonatal medicine. Gray literature was also surveyed, and the search encompassed all study designs and languages up to June 2024. Furthermore, citations and reference lists of relevant articles were scrutinized to identify additional pertinent literature. Ambroxol has demonstrated promising effects in preventing and managing respiratory distress syndrome (RDS). It can enter the placental circulation and rapidly build up in human lung tissue to a much greater extent than in plasma. It promotes fetal lung maturation, surfactant production, and alveolar expansion. Numerous studies have demonstrated the efficacy of antenatal and postnatal ambroxol in the prevention and treatment of RDS. Ambroxol has the potential to be administered intravenously or through nebulization, offering the hopeful possibility of reducing the high failure rate typically associated with non-invasive ventilation in extremely preterm infants, instilling a sense of hope and optimism about the potential of ambroxol. It also shows potential in treating bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal infections. Ambroxol has been observed to assist in the closure of patent ductus arteriosus in preterm infants by inhibiting vasodilator agents such as nitric oxide and exerting vasoconstrictive properties. However, these biological actions may raise concerns regarding the potential induction of pulmonary hypertension and an increased risk of necrotizing enterocolitis. The present scoping review also examines the clinical evidence and the potential of ambroxol in reducing the incidence of intraventricular hemorrhage in preterm infants. Ambroxol may have potential analgesic properties in managing neonatal pain, and as it can penetrate the blood-brain barrier, it suggests potential neuroprotective properties. These properties may encompass the modulation of microglial activation and the antagonistic impact on glutamate receptors. Ambroxol's attributes could contribute to a decreased susceptibility to neurological complications and have demonstrated anticonvulsant effects in preclinical studies. While low-to-moderate-quality evidence indicates potential applications of ambroxol in neonatal care, further research is needed to determine the drug's optimal dosing, timing, and safety profiles in this patient population. We need to investigate ambroxol's potential synergistic effects with antenatal steroids. Exploration is required to assess ambroxol's potential in reducing the high failure rate associated with non-invasive respiratory support for RDS. Lastly, comprehensive studies on the long-term neurodevelopmental outcomes of neonates exposed to ambroxol are essential.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation

BackgroundAntenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function.MethodsDate-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection.ResultsPreterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration (“Prion Disease”, “Alzheimer’s Disease”, “Arachidonic Acid metabolism”). Adverse changes were independent of respiratory function during ventilation.ConclusionsOur data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Does exogenous glucocorticoid administration during pregnancy precipitate the timing of labor? A scoping review.

To investigate whether synthetic (s) glucocorticoids (GCs) administered between the 24th and the 34th gestational weeks in pre-term labor might precipitate labor, studies on sGCs administration were reviewed. The physiology of endogenous glucocorticoid-related increase in fetal-maternal circulation and its association with labor, followed by a scoping review of studies on exogenous sGCs administered for fetal lung maturation and the timing of labor, were included. The methodology of systematic reviews was followed. MEDLINE, Cochrane Library, and Google Scholar databases were searched until October 2023, for original studies investigating the administration of sGCs in pregnancies risking pre-term labor. Duplicates were removed, and 1867 abstracts were excluded as irrelevant. Six controlled and four non-controlled studies were included. The index group consisted of 6001 subjects and 7691 controls in the former, while in the latter, the index group consisted of 2069 subjects. In three out of the six controlled studies, gestational age at labor was significantly lower in sGC-treated women than in controls, while in three studies, gestational age at labor was lower in sGC-treated women than in controls, with a trend toward statistical significance. In one study, gestational age at labor was significantly lower in controls than in sGC-treated women. In the non-controlled studies, the majority of women delivered less than 1 week from the day of sGC administration. In this scoping review, studies lack homogeneity. However, in the controlled studies, a pattern of earlier labor emerges among sGC-treated pregnant women. The use of multiple courses of antenatal sGCs appears to be associated with precipitated labor. Their use should be carefully weighed. Carefully designed trials should examine this ongoing scientific query.

Nrf2 deficiency exacerbated pulmonary pyroptosis in maternal hypoxia-induced intrauterine growth restriction offspring mice

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5 % O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

Peripartum Torpor: A Chilling Case Report and Review of the Literature

Purpose: To report a rare case of peripartum maternal hypothermia and bradycardia. Methods: Case report. Results: Torpor is a transient state of hibernation with hypothermia and bradycardia. Hypothermia is defined as an abnormally low core body temperature less than 36°C.1 Sinus bradycardia is defined as less than 60 beats/min. While occasionally hypothermia or bradycardia is seen in obstetric patients undergoing vaginal delivery, when combined together, it can be a rare, life-threatening state that requires prompt intervention to prevent adverse maternal and fetal outcomes. A 23 year-old G2P0102 at 33+3 weeks of gestation was admitted to the high risk obstetric service for preterm labor complicated by fetal growth restriction. She had a history of preeclampsia in a previous pregnancy, but otherwise denied any chronic medical problems. Upon arrival, her vital signs showed a temperature of 37°C, a pulse of 53 bpm, and blood pressure of 126/62 mmHg. Her white blood cell count was 12.4 x 109/L and hemoglobin was 11.3 g/dL. She received betamethasone for fetal lung maturity and penicillin for Group B streptococcus prophylaxis. As her cervix continued to dilate, she received an epidural for pain management. Once she was in active labor, she became bradycardic with a pulse in the 30s-40s bpm, as confirmed by EKG. She was completely asymptomatic at this time, and fetal heart tones were reassuring with a baseline between 110’s-130’s bpm. She delivered vaginally with 150 mL of estimated blood loss, and her bradycardia continued postpartum even after the epidural was discontinued. When she complained of feeling cold, multiple attempts with different oral and axillary thermometers could not obtain a reading. She was warmed with forced-air warming blankets, warmed blankets, and hot packs in her groin and axilla. During this time, discussion with the NICU staff revealed that her baby was also hypothermic at 33.3°C and hypoglycemic at 28 mg/dL at birth. Other than feeling cold, the patient continued to be asymptomatic despite hypotension and bradycardia. She appeared somnolent but was responsive to questions. Her uterus was firm with minimal vaginal bleeding and no purulent or foul-smelling vaginal discharge. Repeat laboratory testing revealed a white blood count of 19 x 109/L and lactate was 3.3 mmol/L. Her comprehensive metabolic panel was unremarkable. A chest x-ray was clear. A C-reactive protein was &lt; 0.3 mg/dL and sedimentation rate was 14 mm/h. A rectal continuous thermometer was placed, which eventually recorded a temperature at 33.3°C and upon recheck was 31.7°C. A multidisciplinary team, including Anesthesia, Internal Medicine, and Neurology, evaluated the patient due to concern for a central nervous system insult. She received fluid resuscitation and broad-spectrum antibiotics for sepsis protocol. Due to the concern for potential septic shock, the decision was made to transport her to the Medical ICU for further management. As she was leaving Labor &amp; Delivery, her temperature had increased to 36.9°C and her pulse to 61. Thyroid studies the next day revealed a normal Free T4 of 1.00 ng/dL and a high thyroid stimulating hormone level of 9.55 uIU/mL. However, despite an extensive workup, no clear etiology of her hypothermia and bradycardia was identified. Intervention with fluids and application of forced-air warming system resolved the hypothermia in less than 6 hours without relapse. Antibiotics were discontinued after one day due to low suspicion for systemic infection. She remained vitally stable and was discharged on postpartum day 2 without further complications. Conclusions: Maternal hypothermia is relatively common during cesarean delivery; however, very few cases report maternal hypothermia during vaginal delivery. An English language literature search for maternal hypothermia during vaginal delivery yielded less than 10 case reports – few of which identified a cause of the hypothermia – and none of which reported simultaneous maternal bradycardia. While our case is a very rare presentation and the etiology is still unknown, it highlights the importance of prompt recognition of vital sign derangements in peripartum patients as well as multidisciplinary attention.

Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow-up study.

Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence. Prospective observational follow-up study involving twenty-one 14- to 15-year-old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty-five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention-deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus-pituitary-adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference -2.0, 95% confidence interval [CI]: -7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress-induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency-adjusted means: 16.0 Hz vs 17.8 Hz, mean difference -1.83 Hz, 95% CI: -3.21 to -0.45, p = 0.01). In 14- to 15-year-old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow-up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.

The Proportions of Term or Late Preterm Births After Exposure to Early Antenatal Corticosteroids, and Outcomes: Systematic Review and Meta-Analysis of 1.6 Million Infants

(BMJ. 2023;382:e076035 | doi: 10.1136/bmj-2023-076035 l. http://dx.doi.org/10.1136/bmj-2023-076035) Preterm birth is a major cause of morbidity and mortality in both newborns and children. Women at risk of preterm delivery often receive antenatal corticosteroids, depending on their gestational age. These steroids enhance fetal lung maturation; however, unnecessary corticosteroid exposure is a concern. Guidelines recommend tracking and minimizing such exposure to discourage overuse. Animal studies indicate potential risks to fetal brain development and long-term health. This systematic review explored the outcomes of infants exposed to early antenatal corticosteroids, emphasizing the importance of their reasonable use in mitigating risks.

Systematic Quantitative Analysis of Fetal Dexamethasone Exposure and Fetal Lung Maturation in Pregnant Animals: Model Informed Dexamethasone Precision Dose Study.

Dexamethasone (DEX) was applied in neonatal respiratory distress syndrome treatment of pregnant women. We established a pharmacokinetics (PK)/pharmacodynamics(PD)/end point model of pregnant animals based on published data and then extrapolated to simulate fetal exposure and lung maturation in pregnant women. We first established the PK/PD/end point model for DEX in pregnant sheep. We considered the competitive effect of cortisol (Cort) and DEX binding with glucocorticoid receptor and then used the indirect response model to describe disaturated-phosphatidylcholine (DSPC) dynamics. Based on that, we established a regression relationship between DSPC and fetal lung volume (V40). We then extrapolated the PD/end point model of pregnant sheep to pregnant monkeys by corrected stages of morphologic lung maturation in two species. Finally, we utilized the interspecies extrapolation strategy to simulate fetal exposure (AUC0-48h) and V40 relationship in pregnant women. The current model could well describe the maternal-fetal PK of DEX in pregnant animals. Simulated DEX AUC0-24h values of the umbilical venous to maternal plasma ratio in pregnant sheep and monkeys were 0.31 and 0.27, respectively. The simulated Cort curve and V40 in pregnant sheep closely matched the observed data within a 2-fold range. For pregnant monkeys, model-simulated V40 were well fitted with external verification data, which showed good interspecies extrapolation performance. Finally, we simulated fetal exposure-response relationship in pregnant women, which indicated that the fetal AUC0-48h of DEX should not be less than 300 and 100 ng/mL·hr at GW28 and GW34 to ensure fetal lung maturity. The current model preliminarily provided support for clinical DEX dose optimization.

Comparison of Hyperglycemic Effects of Antenatal Administration of Dexamethasone in Gestational Diabetes: A Study of Recommended Versus Predicted Split Doses Regimens

Objective: To compare three consecutive days of hyperglycemic response following antenatal Dexamethasone regimens of 12mg or 6mg in diet-controlled gestational diabetes, administered for fetal lung maturity. Study Design: Quasi-experimental study Place and Duration of Study: Department of Obstetrics and Gynaecology, Combined Military Hospital, Kharian Pakistan, from Oct 2020 to Mar 2021. Methodology: Forty women who met inclusion criteria were selected and assigned to two Groups. Group-A was administered quartered 24 mg steroids 6 hours daily, and Group-B was administered halved 24mg 12 hours daily. Blood sugar levels (BSL) were recorded before and after meals, thrice a day for three consecutive days, and on proforma. Results: Among the selected patients, the mean age was 25.5±2.9 years, and the mean gestational age (duration of pregnancy) was 30.3±2.0 weeks. Out of six blood sugar levels recorded daily for three consecutive days, the episodes of hyperglycemia in the (Group-B) 12-hourly steroid dose were found to be less significant than those in the (Group-A) split 6-hourly dose. Conclusion: The recommended 12 mg, twice-a-day regimen of antenatal corticosteroids was better than the proposed 6mg, four times a day regimen as it caused fewer hyperglycemic episodes in gestational diabetics.

Correlation between cerebroplacental doppler ratio and neonatal respiratory disorders: A reference marker of fetal lung maturation.

The aim of this study was to investigate the role of cerebroplacental ratio (CPR) in the final prenatal care for neonatal respiratory diseases and to analyze the risk of relevant factors associated with neonatal respiratory disorders. A prospective cohort study of 795 singleton pregnancies was conducted. The pulsatility indices (PI) of the umbilical artery (UA) and the middle cerebral artery (MCA) were measured, and the MCA to UA ratio (CPR) was determined. The severity of the case is determined by whether or not the newborn has respiratory problems. Compare the CPR correlation between the two groups and examine the illness prediction factors through a binary logistic regression method. Of the 795 participants, 124 had neonatal respiratory disorders. The mean values of CPR between neonatal respiratory diseases group and control group were 1.78±0.6, 1.97±0.9, respectively (P < 0.001). Maternal age, abortion history, cesarean section history, placental thickness, placental maturity, and amniotic fluid index (AFI) were determined to have no significant link between the two groups after comparison analysis (P > 0.05). It could be found that compared with the control group, CPR MoM indicators of neonatal respiratory distress syndrome, neonatal pneumonia and wet lung disease all show significant decreases. In binary logistic regression analysis, among the variables included in the model, CPR (OR:2.90, P = 0.015), fetal heart monitoring (OR:5.26, P < 0.001), delivery mode (OR:2.86, P < 0.001) and gestational age of delivery (OR:0.92, P < 0.001) were statistically significant in both groups. The findings of this study showed that infant respiratory problems were substantially related to CPR value. The correlation indicates that CPR was a powerful reference marker for respiratory disorders.

Higher prenatal anxiety predicts lower neonatal hair cortisol

BackgroundPrenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. MethodPregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75–2.00). ResultsBoth higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: β = −0.614, p =.012; slope: β = −0.681, p =.006), but not general anxiety (intercept: β = −0.389, p =.114; slope: β = −0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. ConclusionCortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review.

Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

Validity of ductus arteriosus indices added to other ultrasound and Doppler parameters as markers of fetal lung maturity in pregnancy-induced hypertension

Abstract Aim of work To determine the relationship between the gestational age and the (PSV, RI and PI) of the ductus arteriosus and lung maturity and to determine the effect of pregnancy-induced hypertension on these parameters. Material and methods A prospective cohort study was carried out, in which 90 pregnant women at gestational age 34–40 weeks were selected, 50 as a control and 40 with pregnancy-induced hypertension (PIH). They underwent measurement of ductus arteriosus (DA) (PSV, RI and PI) and observing the percentage of the development of neonatal RDS in control and PIH cases. Results There was a direct correlation between the PSV, PI, RI of ductus arteriosus and development of neonatal RDS. A cutoff value for GA, PSV, RI and PI for prediction of the subsequent development of RDS was determined in control ((35.7, 89.9, 0.80, 2.14), with sensitivity (71.4, 100, 85.7, 85.7%) and specificity (93, 97.7, 97.7, 93%), respectively), and PIH (35.7, 91.1, 0.80, 2.14), with sensitivity (71.4, 100, 85.7, 100%) and specificity (71.7, 100, 85.7, 100%), respectively). Conclusions We concluded from our study that for the detection of fetal lung maturity in fetuses of GA from 34 to 40 weeks, it is better to combine GA, PSV, RI and PI of DA to detect lung maturity in control and PIH groups to get more accurate results.