Mechanism of neonatal hypoglycemia after late preterm steroids: are fetal metabolic effects responsible?
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ABSTRACT:
SUBMITTER: Battarbee AN
PROVIDER: S-EPMC9308675 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Mechanism of neonatal hypoglycemia after late preterm steroids: are fetal metabolic effects responsible?
Battarbee Ashley N AN Sandoval Grecio J GJ Gyamfi-Bannerman Cynthia C Blackwell Sean C SC Tita Alan T N ATN Reddy Uma M UM Jain Lucky L
American journal of obstetrics and gynecology 20220329 2
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Project description:ObjectiveIn the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia.Study designSecondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate.ResultsOf 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18).ConclusionIn this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure.Key points· Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..
| S-EPMC8626537 | biostudies-literature
Project description:ImportanceThe Antenatal Late Preterm Steroids (ALPS) trial demonstrated a 20% reduction in the risk of respiratory complications in neonates at risk for a late-preterm birth who were exposed to antenatal corticosteroids compared with those who were not.ObjectiveTo assess whether new evidence of steroid administration for neonatal respiratory benefit in the late-preterm period is associated with changes in obstetric practice and the use of assisted ventilation for the neonate after delivery.Design, setting, and participantsThis cross-sectional study of US births from February 1, 2015, to October 31, 2017, as ascertained from US natality data, included live-born, singleton neonates born between 34 and 36 completed weeks of gestation to people without pregestational diabetes. An interrupted time series analysis using Poisson regression models was conducted. Data were analyzed from July 11, 2022, to November 9, 2022.ExposuresPublic dissemination of the ALPS trial results, which occurred during a 9-month period from February 1, 2016 (first published online), to October 31, 2016 (time of the last major professional society's guideline update in the months after the trial's publication).Main outcomes and measuresSteroid use, any assisted ventilation use, and assisted ventilation use for more than 6 hours immediately after the dissemination period.ResultsA total of 707 862 births were included, divided among the 12-month predissemination period (n = 250 643), dissemination period (n = 195 736), and 12-month postdissemination period (n = 261 493). Most births were at 36 weeks of gestation (53.9% in the predissemination and postdissemination period; P = .10). Small but significant differences were found between the predissemination and postdissemination period cohorts: there were more individuals 35 years or older (19.5% vs 17.9%), fewer White individuals (67.8% vs 69.8%), and more publicly insured individuals (50.5% vs 50.1%) in the postdissemination period compared with the predissemination period, respectively (P < .001 for all). Compared with what rates were expected based on the predissemination trends, the adjusted rate of steroid use increased from 5.0% to 11.7% (adjusted incidence rate ratio [IRR], 2.34; 95% CI, 2.13-2.57), and assisted ventilation use decreased from 8.9% to 8.2% (adjusted IRR, 0.91; 95% CI, 0.85-0.98) after the dissemination period. No change was observed in assisted ventilation use for more than 6 hours (adjusted IRR, 0.98; 95% CI, 0.87-1.10).Conclusions and relevanceThese findings suggest that there was an immediate change in practice of administering antenatal steroids and a reduction in neonatal morbidity among late-preterm births associated with the dissemination of the ALPS trial, suggesting that this evidence may be translating into a reduction in immediate respiratory morbidity outside the context of a clinical trial.
| S-EPMC9118048 | biostudies-literature
Project description:BackgroundLate preterm steroid administration can induce transient maternal and thus fetal hyperglycemia, which can increase production of fetal insulin and C-peptide. Infants delivered in this setting are subsequently at increased risk for hypoglycemia. Although maternal glycemic control before delivery is a key component of care for parturients with diabetes, this intervention has not been studied in the setting of late preterm steroid administration.ObjectiveThis study aimed to determine the effect of maternal screening for and treatment of hyperglycemia after late preterm steroid administration on fetal C-peptide levels and other metabolic markers.Study designThis was a multicenter, randomized trial (NCT03076775) of nondiabetic parturients with a singleton gestation receiving betamethasone at 34 0/7 weeks to 36 5/7 weeks for anticipated preterm birth. Participants randomized to maternal glycemic control received fasting and 1-hour postprandial or serial intrapartum capillary blood glucose screening with insulin treatment as indicated. Those randomized to expectant management did not receive any glucose screening or treatment. The primary outcome was fetal C-peptide level measured from umbilical cord blood at delivery. Secondary outcomes included other fetal metabolic markers and neonatal hypoglycemia (glucose level <40 mg/dL). Baseline characteristics and outcomes were compared between the groups. We estimated that we would need a sample size of 144 to provide >90% power to show a 1 ng/mL decrease in C-peptide concentration (±1.5 ng/mL) at ⍺=0.05 using a 2-sample t test and 1 interim analysis. After the interim analysis, the trial was stopped for futility.ResultsOf 491 screened parturients, 163 (33%) were deemed eligible and 86 (53%) were randomized to 1 of the treatment groups (June 2017 to February 2021). One person was lost to follow-up because of delivery at another hospital. Baseline characteristics were similar between groups. The median interval from betamethasone administration to delivery was 24 hours (interquartile range, 13-96 hours) and did not differ between groups (P=.82). Most (82%) randomized to maternal glycemic control had hyperglycemia: 80% had at least 1 fasting glucose level >95 mg/dL, 75% had at least one 1-hour postprandial glucose level >140 mg/dL, and 80% had at least 1 intrapartum glucose level >110 mg/dL. In addition, 15% had at least 1 glucose level >180 mg/dL. None had maternal hypoglycemia after insulin treatment. Compared with expectant management, maternal glycemic control did not affect the median fetal C-peptide level (1.02; interquartile range, 0.52-1.85 vs 1.09; interquartile range, 0.61-1.65; P=.97) or other metabolic markers. Maternal glycemic control also did not affect neonatal hypoglycemia (49% vs 51%; P=.83) or other secondary neonatal or maternal outcomes. There was no evidence of effect modification by gestational age or body mass index at randomization, indication for betamethasone, duration from betamethasone to delivery, maternal race or ethnicity, or neonatal sex. In addition, the results were unchanged in a sensitivity analysis using a per-protocol approach.ConclusionMaternal hyperglycemia was observed in most nondiabetic parturients after receiving late preterm betamethasone. However, there was no improvement in fetal metabolic status, neonatal hypoglycemia, or other neonatal or maternal outcomes with maternal glycemic control. Therefore, maternal glucose surveillance and treatment does not seem to be beneficial in nondiabetic parturients receiving late preterm steroids.
| S-EPMC9195161 | biostudies-literature
Project description:BackgroundThe external validity of randomised trials can be compromised when trial participants differ from real-world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real-world treatment benefits.ObjectivesTo estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real-world populations.MethodsIndividual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population-based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000-2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re-estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population-based (real-world) sample.ResultsThe real-world absolute risk reduction was estimated to be -2.2 (95% CI -4.6, 0.0) cases of respiratory morbidity per 100, compared with -2.8 (95% CI -5.3, -0.3) in original trial data. Corresponding NNTs were 46 in the real-world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of -3.7 vs. -1.2 per 100 respectively).ConclusionsThe absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real-world situation.
| S-EPMC9250943 | biostudies-literature
Project description:Despite India having a high burden of infant deaths and preterm birth, there is a clear lack of studies documenting association between preterm birth and infant mortality in India. Additionally, existing studies have failed to account for unobserved heterogeneity while linking preterm birth with infant mortality. Hence, the present study examines association of preterm birth with early neonatal death (ENND), late neonatal death (LNND), and postneonatal death (PNND) in India. We used the reproductive calendar canvassed in the cross-sectional National Family Health Survey 2015-16 (NFHS-4) to identify preterm births. We used multivariable logistic regression to examine the associations for all births, most-, second most-, and third most- recent births occurred in five years preceding NFHS-4. We use mother fixed-effect logistic regression to confirm the associations among all recent births. Among all births, preterm births were 4.2, 3.8, and 1.7 times as likely as full-term births to die during early neonatal, late neonatal, and postneonatal periods respectively. Among most recent births, preterm births were 4.4, 4.0, and 2.0 times as likely as full-term births to die during early neonatal, late neonatal, and postneonatal periods respectively. Preterm births were also associated with risk of only ENND, LNND, and PNND among the second most recent births. Preterm births were associated with risk of only ENND and LNND among the third most recent births. Preterm births were also associated with ENND, LNND, and PNND in the mother fixed-effects regressions. This study establishes associations of preterm birth with ENND, LNND, and PNND in India using over 0.2 million births that occurred in 5 years preceding one of the largest population-based representative household surveys conducted in any part of the world. Our findings call for programmatic and policy interventions to address the considerable burden of preterm birth in the country.
| S-EPMC10021707 | biostudies-literature
Project description:ObjectiveTo develop and validate a telesimulation scenario for nursing students in the care of late preterm infants with hypoglycemia.MethodsA methodological study conducted between August 2021 and May 2022 in a virtual environment involved constructing and validating the scenario with 10 experts, and testing it with 10 students. The content validity index assessed validity, with a threshold of 80% or higher, and suggestions were analyzed using semantic approximation.ResultsValidation confirmed the appropriateness of all 14 scenario items, with an overall index of 97.8% and clarity and relevance indices of 98.5%. During testing, the overall index was 99.7%, with the "resources" item receiving the lowest score. Adjustments were made to objectives, technical terms, resources, and target audience based on feedback.ConclusionTelesimulation is a widely accepted educational technology for training nursing students, with potential to enhance teaching quality and neonatal care.
| S-EPMC10704675 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pgph.0000205.].
| S-EPMC10072339 | biostudies-literature
Project description:Background: Infants born preterm or small for gestational age (SGA, due to fetal growth restriction) both show an increased risk of neonatal infection. However, it remains unclear how the co-occurrence of preterm birth and SGA may affect neonatal immunity and infection risk. We hypothesized that fetal growth restricted (FGR) preterm newborns possess impaired immune competence and increased susceptibility to systemic infection and sepsis, relative to corresponding normal birth weight (NBW) newborns. Methods: Using preterm pigs as a model for preterm infants, gene expression in lipopolysaccharide (LPS) stimulated cord blood was compared between NBW and FGR (lowest 25% birth weight percentile) preterm pigs. Next, clinical responses to a systemic Staphylococcus epidermidis (SE) challenge were investigated in newborn FGR and NBW preterm pigs. Finally, occurrence of spontaneous infections were investigated in 9 d-old FGR and NBW preterm pigs, with or without neonatal antibiotics treatment. Results: At birth, preterm FGR piglets showed diminished ex vivo cord blood responses to LPS for genes related to both innate and adaptive immunity, and also more severe septic responses following SE infection (e.g., higher blood lactate, decreased blood pH, neutrophil and platelet counts, relative to NBW pigs). After 9 d, FGR pigs had higher incidence and severity of spontaneous infections (e.g., higher bacterial densities in the bone marrow), increased regulatory T cell numbers, reduced neutrophil phagocytosis capacity, and impaired ex vivo blood gene responses to LPS, especially when receiving neonatal antibiotics. Conclusion: FGR at preterm birth is associated with poor immune competence, impaired infection resistance, and greater sepsis susceptibility in the immediate postnatal period. Our results may explain the increased morbidity and mortality of SGA preterm infants and highlight the need for clinical vigilance for this highly sensitive subgroup of preterm neonates.
| S-EPMC7438575 | biostudies-literature
Project description: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.
| S-EPMC11346182 | biostudies-literature