Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy

doi:10.1067/mob.2000.108838

American Journal of Obstetrics and Gynecology

Volume 183, Issue 4, October 2000, Pages 810-814

https://doi.org/10.1067/mob.2000.108838 Get rights and content

Abstract

Objective: This study was undertaken to compare the effects of single versus multiple courses of betamethasone therapy on the frequencies of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. Study Design: We performed a nonconcurrent prospective analysis of singleton pregnancies delivered between 24 and 34 weeks’ gestation after antenatal betamethasone exposure. Patients were categorized into two groups according to betamethasone exposure: (1) two 12-mg doses in a 24-hour interval on admission (single-course group) and (2) repeated dosing after the initial single course (multiple-course group). All patients received prophylactic antibiotics for group B streptococci. Any patients with ruptured membranes for >24 hours before delivery were excluded. Data were analyzed with the Student t test, the χ² test, and the Fisher exact test. Multiple logistic regression analyses were performed to examine the effect of each steroid dosing regimen on early-onset neonatal sepsis and neonatal death. P < .05 was considered significant for all 2-tailed tests. Results: A total of 453 patients were included, with 267 in the single-course group and 186 in the multiple-course group. The two groups were similar with respect to maternal demographic characteristics, gestational age at delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization. Multiple courses were significantly associated with early-onset neonatal sepsis (odds ratio, 5.00; 95% confidence interval, 1.3-23.2), chorioamnionitis (odds ratio, 9.96; 95% confidence interval, 2.1-64.6), endometritis (odds ratio, 3.61; 95% confidence interval, 1.7-8.1), and neonatal death (odds ratio, 2.92; 95% confidence interval, 1.3-6.9). The frequencies of the other neonatal outcomes analyzed, including respiratory distress syndrome and grade III or IV intraventricular hemorrhage, were similar between the 2 groups. Multiple logistic regression analyses confirmed that multiple courses of antenatal betamethasone were independently associated with early-onset neonatal sepsis (odds ratio, 1.25; 95% confidence interval, 1.1-1.9) and neonatal death (odds ratio, 1.70; 95% confidence interval, 1.1-1.9). Conclusions: Multiple courses of antenatal betamethasone are associated with increased risks of perinatal infectious morbidity and neonatal death. (Am J Obstet Gynecol 2000;183:810-4.)

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During pregnancy, the maternal body undergoes a considerable transformation regarding the anatomy, metabolism, and immune profile that, after delivery, allows for protection and nourishment of the offspring via lactation. Pregnancy hormones are responsible for the development and functionality of the mammary gland for breast milk production, but little is known about how hormones control its immune properties. Breast milk composition is highly dynamic, adapting to the nutritional and immunological needs that the infant requires in the first months of life and is responsible for the main immune modeling of breastfed newborns. Therefore, alterations in the mechanisms that control the endocrinology of mammary gland adaptation for lactation could disturb the properties of breast milk that prepare the neonatal immune system to respond to the first immunologic challenges. In modern life, humans are chronically exposed to endocrine disruptors (EDs), which alter the endocrine physiology of mammals, affecting the composition of breast milk and hence the neonatal immune response. In this review, we provide a landscape of the possible role of hormones in the control of passive immunity transferred by breast milk and the possible effect of maternal exposure to EDs on lactation, as well as their impacts on the development of neonatal immunity.
The fetal fibronectin test is superior to cervical length measurement in predicting preterm birth in twin pregnancies: a retrospective observational study
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Citation Excerpt :
In addition, antenatal corticosteroids are considered to induce adverse maternal effects including adrenal suppression and altered glucose tolerance [4]; the degree of modification of the maternal fasting plasma glucose and insulin levels might also correlate with a twin pregnancy status [5]. It has been reported that multiple courses of glucocorticoids are associated with adverse perinatal outcomes [6], so that the indications for hospital admission with subsequent tocolysis and glucocorticoid prophylaxis should be questioned [7,8]. Furthermore, diminishing effects of glucocorticoids in inducing fetal lung maturation after 7 days are suggested.
Twin pregnancies have a higher likelihood to experience spontaneous preterm birth (PTB). Those with imminent PTB need to be determined in order to undergo fetal lung maturation with glucocorticoids and therewith improve neonatal outcomes. The aim of this study was to assess the predictive value of the fetal fibronectin (fFN) test and the measurement of cervical length in twin pregnancies with symptoms of imminent PTB.
We performed an observational study on all twin pregnancies at the Medical University Vienna. Women were admitted to the hospital either due to symptoms of imminent PTB or due to a shortening of the cervical length before completed 34 weeks of gestational age. Logistic regression analysis was performed to assess the predictive value of the fFN test and cervical length on imminent preterm birth.
The data of 82 women with twin pregnancies were eligible, of which 10 (12 %) had a positive, 45 (55 %) a negative, 21 (26 %) an unclear fFN result, and 6 (7 %) showed missing data. Cervical length ≤20 mm did not show any statistical significant prediction of PTB in our study cohort. After 7 days, 4/10 (40 %) pregnant women with positive fFN test gave birth, while 4/45 (9 %) women with a negative fFN test gave birth. Within 14 days after hospitalization, 6/10 (60 %) women with a positive fFN test gave birth, compared to 4/45 (9 %) with a negative fFN test. The positive fFN test was a statistically significant predictor of PTB within 7 days (p = 0.02) and 14 days (p = 0.004), respectively.
The fFN test has the potential to detect women with twin pregnancies, who are at risk of giving birth within the following days. Hence, the practice of hospitalizing women solely due to the shortening of the cervical length cannot be supported.
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A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial
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Citation Excerpt :
However, we did not collect process data to test such a hypothesis. Findings from both animals and human beings suggest that antenatal corticosteroids can affect fetal growth, especially if several courses are used.34,36 Additionally, reductions in birthweight associated with antenatal corticosteroids have been reported in infants born at a gestational age of 36 weeks or older in at least one study.3
Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries.
In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096.
The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47 394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50 743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87–1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33–2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02–1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48 219 women in the intervention group and 867 (2%) of 51 523 in the control group (OR 1·45, 1·33–1·58, p<0·0001).
Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased.
Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Effects of antenatal corticosteroids on neonatal outcomes in very-low-birth-weight preterm newborns: A 10-year retrospective study in a medical center
2012, Pediatrics and Neonatology
To evaluate the effects on neonatal outcomes between very-low-birth-weight (VLBW) preterm newborns with and without maternal use of antenatal corticosteroids (ACS).
We retrospectively reviewed medical records of VLBW premature infants who were admitted to Kaohsiung Medical University Hospital between 1999 and 2008. A total of 256 infants were enrolled in this study. A total of 174 neonates did not receive any ACS, and 82 neonates received ACS. A total of 37 neonates received one dose of ACS, and 45 neonates received more than one dose of ACS, referred to as “multiple-dose ACS.” In addition, these 82 infants were divided to betamethasone group (n = 8) and dexamethasone group (n = 50) with 24 infants excluded because of inadequate information.
Neonates with multiple-dose ACS had lower incidence of surfactant use and lower rate of intubation than neonates without ACS. There were no differences in the occurrences of intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and chronic lung disease with one-dose vs. multiple-dose ACS and in the betamethasone group vs. the dexamethasone group.
ACS reduces the need for exogenous surfactant, and the need for endotracheal tube insertion at birth in VLBW premature infants.
Perinatal outcomes depending on the doses of betamethasone administered in pregnant women
2009, Progresos de Obstetricia y Ginecologia
Evaluar los resultados perinatales entre diferentes dosis de corticoides antenatales.
Estudio retrospectivo de 61 gestaciones únicas con amenaza de parto prematuro, sin otra patología asociada, y con al menos una dosis estándar de betametasona por vía intramuscular (2 dosis de 12 mg/24 h). Dos grupos de estudio: grupo 1: dosis estándar, y grupo 2: una o más dosis adicionales semanales de 12 mg de betametasona. Variables maternas: semanas de gestación al inicio del tratamiento corticoideo, semanas al parto, tipo de parto, patología puerperal, entre otras; variables neonatales: sexo, índice de Apgar, peso, talla, perímetro cefálico y patología neonatal. Se realizó un estudio descriptivo y comparativo de ambos grupos.
No hubo diferencias estadísticamente significativas en los grupos. Sin embargo, se registraron más casos de displasia broncopulmonar (p = 0,09) en el grupo 1.
La repetición semanal de las dosis de corticoides no mejora los resultados perinatales ni asocia efectos adversos.
To evaluate perinatal outcomes between different doses of antenatal corticosteroids.
Retrospective study of 61 single pregnancies at risk of premature birth, with no other associated pathology and with at least one standard dose of intramuscular betamethasone (two doses of 12 mg/24h). There were two study groups: Group 1: standard dose, and Group 2: one or more additional weekly doses of 12 mg. Maternal variables: gestational weeks at the beginning of steroid treatment, weeks at delivery, type of birth, puerperal pathology; neonatal variables: sex, Apgar score, weight, height and cephalic perimeter at birth, and neonatal pathology. We performed a descriptive and comparative study on both groups.
No statistically significant differences were found between the groups. However, there were more cases of bronchopulmonary dysplasia (P=.09) in group 1.
Repeated weekly doses of corticosteroids do not improve perinatal outcomes and are not associated with adverse effects.

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Transactions of the Twentieth Annual Meeting of the Society for Maternal-Fetal MedicineNeonatal sepsis and death after multiple courses of antenatal betamethasone therapy

Abstract

Transactions of the Twentieth Annual Meeting of the Society for Maternal-Fetal Medicine
Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy