Efficacy of a single dose of antenatal corticosteroids on morbidity and mortality of preterm infants

OBJECTIVE: To assess the effectiveness of an incomplete course of antenatal corticosteroids (ACS) on neonatal morbidity and mortality of preterm infants. METHODS: Preterm infants born at 25-34 weeks' gestational age between January 1, 1998 and December 31, 2003 were included in this study. Studied infants were divided in two groups: the ACS group included those infants who had been exposed to a single 12-mg dose of betamethasone before delivery while the control group included those infants who had been delivered without any antenatal corticosteroids treatment. The most important neonatal outcomes were compared between the two groups. RESULTS: One hundred and seventy neonates (41.4%) were exposed to one 12-mg dose of betamethasone before delivery, while 241 neonates (58.6%) did not receive any antenatal corticosteroids treatment. Mean gestational age at delivery (30.4+/-2.4 weeks versus 31.2+/-2.9 weeks, p=0.004) and mean birth weight (1375+/-454 g versus 1625+/-580 g, p<0.001) were lower in the ACS group. The univariate analysis showed that delivery room intubation and respiratory distress syndrome were more frequent in the ACS group and that the length of stay was also significantly longer in this group. No differences were found concerning survival, neonatal morbidity, need for and duration of mechanical ventilation and oxygen therapy. The incidence of major outcomes in survivors was also similar. Logistic regression adjusted for gestational age showed that the exposure to a single dose of betamethasone before delivery was not associated with a significant reduction in the rate of any neonatal outcome. We also compared the outcomes in function of gestational age subclasses. In the 25-27 weeks subgroup, delivery room intubation, surfactant treatment and patent ductus arteriosus (PDA) were less frequent in ACS infants; they had also shorter ventilation and oxygen duration. In the 30-31 weeks subgroup, ACS infants had a lower incidence of mechanical ventilation and a shorter duration of oxygen therapy. Finally, no differences were found in the 28-29 weeks subgroup and in the 32-34 weeks subgroup. CONCLUSION: Effects of incomplete antenatal corticosteroids are variable: they give some benefits to infants of 25-27 weeks gestational age, fail to show any difference in outcomes in the 32-34 weeks subgroup and are doubtful between these extremes.     

Use or overuse of antenatal corticosteroids for suspected preterm birth

Abstract

Objectives: To determine the ratio of women who received antenatal steroid for suspected preterm birth (PTB) to those who actually deliver before 34 weeks of gestation at a tertiary care center.

Methods: This is a retrospective study. Data was collected from November 2008 to February 2009 on women who presented with suspected PTB had received corticosteroids (between 26 weeks and 33 weeks-6 days of gestation).

Result: More than two-thirds of the women who received antenatal corticosteroids for suspected PTB actually delivered after 34 weeks.

Conclusion: The ratio of women who received complete dose of steroids for suspected PTB compared to the number of patients who actually deliver prematurely is high raising doubts about the methods employed to diagnose PTB.     

Association between antenatal corticosteroids and neonatal hypoglycemia in indicated early preterm births*

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40?mg/dL) within the first 48?h of neonatal life.

Materials and methods: Retrospective cohort of all indicated singleton preterm births (23?34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40?mg/dL) within the first 48?h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2–7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.

Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48?h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5–3.6). Infants who received a full antenatal corticosteroid course within 2–7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7?d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8–2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250?h, and the lowest neonatal blood sugar in the first 48?h of life.

Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48?h of life. Further studies should validate our findings.     

Evaluation of antenatal corticosteroid prescribing patterns among 984 women at risk for preterm delivery

Abstract

Objective: To evaluate the prescribing patterns of the first antenatal corticosteroids (ACS) course in our tertiary referral centre from 2005 until 2010.

Study design: We conducted a retrospective cohort study including all women who received ACS between 24⁺⁰ and 34⁺⁰ weeks of gestation. Main outcome measure was the number of women who delivered within 7?d after ACS administration. The time interval from administration to delivery was compared between women with different indications. Furthermore, all women delivering between 24⁺⁰ and 34⁺⁰ weeks of gestation who did not receive ACS were identified.

Results: 1008 women received ACS, 15 (1.5%) women were lost to follow up. Main indications were suspected preterm labour, preterm prelabour rupture of membranes, maternal indication, foetal indication and vaginal blood loss (VBL). Overall, 447 (45.4%) women delivered ≤7?d after ACS administration. This percentage was 13.6% in women with VBL and 61.5% in women with maternal indication. During the study period, 1267 women delivered before 34 weeks of gestation, 126 (9.9%) women did not receive ACS.

Conclusions: The time interval from ACS administration to delivery differs per indication. Women with VBL are most often over treated. The timing of the first ACS course should be improved.     

Practice patterns in the timing of antenatal corticosteroids for fetal lung maturity

Objective: To determine the practice patterns of antenatal corticosteroid (AS) administration in women with threatened preterm labor.

Methods: This was a retrospective cohort of patients who received betamethasone between 2009 and 2010, identified through a pharmacy database. Patients with high order multiples; incomplete records and indicated preterm delivery were excluded. Demographic and obstetrical factors were compared between women with an AS to delivery latency of ≤7 days versus >7 days. Parametric and non-parametric tests were used as appropriate. p?<?0.05 denotes statistical significance; relative risks with 95% confidence intervals were calculated.

Results: Three-hundred forty-five patients were included. Sixty-eight patients (20%) received AS within 7 days of delivery. Women who received AS ≤7 days before delivery (optimal timing) were more likely to have a transvaginal cervical length ≤2?cm (RR:2.53, CI: 1.2–5.6), cervical dilation ≥2?cm (RR: 3.86, CI: 2.7–5.6) and positive fFN (RR: 2.59, CI: 1.1–6.3). Preterm premature ruptured membranes were also associated with optimal timing of AS (RR: 4.86, CI: 3.4–6.8).

Conclusions: Eighty percent of patients receive suboptimal timing of AS administration. Factors associated with suboptimal timing are: cervical length >2?cm, cervical dilation <2?cm and negative fFN. Cervical assessment should be a key factor in the decision for AS administration. More research is needed for accurate timing of AS in women with threatened preterm labor.     

Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior

OBJECTIVE: This study was undertaken to determine the effects of repeated courses of antenatal corticosteroids on childhood behavior and disabilities, including cognitive delay and cerebral palsy. STUDY DESIGN: Nonrandomized regional cohort of 541 very preterm infants born in Western Australia from singleton pregnancies and alive at 3 years were included in the study. MAIN OUTCOME MEASURES: Physical, cognitive, and psychological assessments up to 6 years. RESULTS: Increasing numbers of antenatal corticosteroid courses were associated with a reduction in the rate of cerebral palsy. Three or more courses were also associated with increased rates of aggressive/destructive, distractible, and hyperkinetic behavior and these effects were present at both ages 3 and 6 years. Measures of internalizing behavior and intelligence quotient were unaffected by antenatal corticosteroid use. CONCLUSION: Repeated antenatal courses of corticosteroids may protect against cerebral palsy but are associated with hyperactivity later in childhood.     

Neurological morbidity in newborn twins

Forty-six twins were compared with an equal number of singletons, matched for gestational age, birthweight and mode of delivery. The neurological findings in the neonatal period were similar in the matched groups, but twins were significantly more often deviant than a large unselected sample of singletons. It is concluded that both in twins and in singletons growth retardation, preterm birth and birth trauma are important causes of neonatal neurological abnormality, but that twins are not more susceptible to the effects of these variables than singletons.     

Medically indicated late preterm delivery and its impact on perinatal morbidity and mortality: a retrospective population-based cohort study

Objective: In the last few decades, attention has been focused on morbidity and mortality associated with late preterm delivery (34–36?+?6/7 weeks), accounting for 60–70% of all preterm births. This study is aimed to determine (1) the prevalence of late preterm deliveries (spontaneous and medically indicated) in our population; and (2) the rate of neonatal morbidity and mortality as well as maternal complications associated with the different phenotypes of late preterm deliveries.

Study design: This retrospective population-based cohort study, included 96,176 women who had 257,182 deliveries, occurred between 1988 and 2011, allocated into three groups: term (n?=?242,286), spontaneous (n?=?10,063), and medically indicated (n?=?4833) late preterm deliveries.

Results: (1) Medically indicated late preterm deliveries were associated with increased maternal morbidity, as well as neonatal morbidity and mortality, in comparison with other study groups (p?Conclusions: (1) Medically indicated late preterm deliveries were independently associated with adverse composite neonatal outcome; and (2) to benefit in term of neonatal outcome from the tool of medically indicated late preterm birth, their proportion should be kept below 35% of all late preterm deliveries, while exceeding this threshold increases the risk of neonatal mortality.     

The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia

Abstract

Objective: While antenatal corticosteroids reduce the risk of neonatal morbidity and mortality, perhaps the maternal hyperglycemia they produce has other neonatal effects. Thus, we sought to examine the association between antenatal betamethasone exposure and neonatal hypoglycemia and hyperbilirubinemia.

Methods: We designed a retrospective cohort study of all preterm deliveries from 32 to 37 weeks of gestation at a single university hospital from 1990 to 2007. Data were collected on antenatal betamethasone administration and the neonatal outcomes. Univariable, multivariable and stratified analyses were conducted.

Results: Of 6675 preterm deliveries, significantly higher rates of neonatal hypoglycemia (5.7% versus 4.2%, p?<?0.05) and hyperbilirubinemia (45.9% versus 24.1%, p?<?0.05) were observed in neonates exposed to antenatal betamethasone. Controlling for potential confounders including gestational age, these findings persisted with betamethasone-exposed neonates 1.6 times more likely to have hypoglycemia (aOR 1.60, 95% CI 1.24–2.07) and 3.2 times more likely to have hyperbilirubinemia (aOR 3.23, 95% CI 2.92–3.58).

Conclusions: Antenatal betamethasone was associated with neonatal hypoglycemia and hyperbilirubinemia. Further work to determine whether this association is related to maternal hyperglycemia should be conducted, given this could be addressed with strict maternal glycemic control during betamethasone administration.     

Effect of antenatal tocolysis on neonatal outcomes

Objective: Detail adverse neonatal effects in pregnancies treated with indomethacin (I), magnesium sulfate (M) or nifedipine (N). Methods: Women in acute preterm labor with cervical dilatation 1–6?cm were randomized to receive one of three first-line tocolytic drugs. Results: There were 317 neonates (I = 103, M = 95, N?=?119) whose mothers were treated with tocolytic therapy. There was no difference in gestational age at randomization (average 28.6 weeks’ gestation) or at delivery (31.6 weeks’ gestation, p?=?0.551), birth weight (p = 0.871) or ventilator days (p = 0.089) between the three groups. Neonatal morbidity was not different between the three groups; respiratory distress syndrome (p?=?0.086), patent ductus arteriosus (p?=?0.592), sepsis (p?=?0.590), necrotizing enterocolitis (p = 0.770), intraventricular hemorrhage (p = 0.669) and periventricular leukomalacia (p?=?0.124). Conclusions: There were no statistically significant differences between the three tocolytics as far as composite neonatal morbidity or mortality was concerned.     

Intra-amniotic corticosteroids for preterm lung maturation in sheep

OBJECTIVE: The purpose of this study was to compare efficacy on fetal lung maturation of intra-amniotic betamethasone or budesonide with the efficacy of maternal intramuscular betamethasone. STUDY DESIGN: Pregnant ewes received intra-amniotic betamethasone (0.5 mg/kg or 2 mg/kg fetal weight), intra-amniotic budesonide (0.5 mg/kg or 2 mg/kg), maternal intramuscular betamethasone (0.5 mg/kg maternal weight), intra-amniotic saline solution, or maternal saline solution. Lambs were delivered 2 or 7 days later, at 124 days of gestation for measurement of respiratory system compliance, ventilatory efficiency index, and surfactant levels. RESULTS: Lung function increased 2 days after maternal betamethasone, intra-amniotic betamethasone (2 mg/kg), and intra-amniotic budesonide (2 mg/kg) administration and 7 days after maternal betamethasone or intra-amniotic budesonide (2.0 mg/kg) administration. Lung function was not improved 7 days after intra-amniotic betamethasone (2.0 mg/kg) administration or 2 days after intra-amniotic betamethasone (0.5 mg/kg) or intra-amniotic budesonide (0.5 mg/kg) administration. Intra-amniotic corticosteroid administration increased fetal death and respiratory morbidity. CONCLUSION: Intra-amniotic corticosteroid administration improved preterm lung function, but the associated morbidity and mortality rates suggest that they are not suitable for clinical use.     

Perinatal mortality and morbidity. Comparison between maternal transport, neonatal transport and inpatient antenatal treatment

The purpose was to assess differences in neonatal morbidity and mortality between maternally transferred, neonatally transferred and inborn neonates. We evaluated a continuous series of all antenatal transported infants (ATI, n=247) and postnatal transported infants (PTI, n=34) to the NICU and all preterm inborns (NTI, n=120) delivered at the University Hospital of Vienna. Data collected included sociodemographic, obstetrical and neonatal data. Mild neonatal morbidity was defined as RDS, BPD, ROP, PDA, NEC or IVH I–II, whereas severe neonatal morbidity was defined as the presence of PVL or IVH III–IV. Data were analyzed statistically using the Spearman correlation Coefficient, the Kruskal-Wallis test, and a multivariate model. There was a substantial gain in gestational age from transfer to delivery in the ATI group and from admission to delivery in the NTI group (2.1 and 5.6 weeks, respectively). The neonatal survival rate was 88.7% in the ATI and 97.5% in the NTI group. No neonate died in the PTI group; there was a significantly higher percentage of severe neonatal morbidity than in the ATI group (11.8% vs. 4.9%). We could not observe a significant difference with respect to the risk of death among the three study groups. There was a strong trend towards higher probability of severe neonatal morbidity in the NTI group. The risk of severe neonatal morbidity is much higher in the PTI-group (rel. risk 0.19, 0.06). Antenatal transfer guaranteed a significantly better neonatal outcome concerning severe neonatal morbidity than postnatal transport, and compared favorably with inborn admissions, even given the higher gestational age and birth weight in the NTI-group. Received: 27 March 2001 / Accepted: 29 March 2001     

A clinical opinion on how to manage the risk of preterm birth in twins based on literature review

Twin pregnancies are prone to preterm birth and consequent morbidity. There is an increasing evidence base concerning the prediction and prevention of preterm birth in singletons, including the reduction of morbidity with therapies such as magnesium sulphate and antenatal corticosteroids. However, the research in twins is less clear, partly due to fewer numbers being investigated, but also evidence is largely based on twins without a previous history. Prophylactic interventions such as cerclage, progesterone and vaginal pessaries are increasingly showing benefit in singleton pregnancies with a prior history and when the cervix is short. Cerclage in twins has not been adequately researched in women with previous preterm birth, and as with singletons should not be used on the basis of a short cervix alone. Vaginal progesterone does not work in twins, but its value in high-risk twins, with a prior history and short cervix is uncertain. The vaginal pessary may be valuable in the twin with a short cervix. Currently, it is reasonable to extrapolate some of the evidence from singletons to twins, e.g. with antenatal corticosteroids and magnesium sulphate. Cerclage, vaginal pessaries and progesterone should not be routinely used in twin pregnancies without an additional high-risk factor such as prior history of preterm birth or short cervix, until further evidence is obtained.     

Optimal timing of antenatal corticosteroids in women with bleeding placenta previa or low-lying placenta*

Background: Administrating a single course of antenatal corticosteroids to women at risk of preterm birth between 24 and 34 weeks of gestation has been shown to decrease neonatal morbidity and mortality. There is evidence that the optimal timing for the administration of antenatal corticosteroids is within 1–7 days before birth as the effect of antenatal corticosteroids has been shown to decline 7 days after administration. Therefore, given that antenatal corticosteroids are the single most effective intervention in cases of preterm birth, efforts should be made to optimize the timing of administration of antenatal corticosteroids.

Objective: To test the hypothesis that the timing of antenatal corticosteroids in women with vaginal bleeding due to placenta previa or low-lying placenta can be optimized by identifying women at low risk of imminent delivery.

Study design: This was a retrospective cohort study of all women admitted to a tertiary referral center at 24–34 weeks’ gestation with vaginal bleeding due to placenta previa or low-lying placenta between 2003 and 2014. Multivariable logistic regression analysis was used to identify factors that are independently associated with delivery within 14 days from admission.

Results: A total of 202 women who met the inclusion criteria were admitted with vaginal bleeding in the presence of placenta previa or low-lying placenta during the study period, of whom 31 (15.3%) and 44 (21.8%) gave birth within 7 and 14 days from admission, respectively. The following factors were independently associated with delivery within 14 days from admission: complete placenta previa (odds (OR) 3.57, 95%CI 1.57–9.03), severe bleeding at presentation (OR 17.14, 95%CI 2.92–100.70), uterine contractions at presentation (OR 6.02, 95%CI 1.91–19.00), and cervical length <25?mm at presentation (OR 6.33, 95%CI 1.37–29.11). A predictive test based on the presence of ≥1 of these risk factors was associated with a sensitivity of 90.9% and a negative predictive value of 94.6% for delivery within 14 days of presentation.

Conclusions: In women presenting with vaginal bleeding due to placenta previa or low-lying placenta, it seems possible to identify a subgroup of women in whom the likelihood of delivery within 14 days is low. This information may allow for selective (rather than routine) administration of antenatal corticosteroids in this scenario, and may thereby contribute to the optimization of the timing of administration of antenatal corticosteroids.