Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birthRespiratory distress syndrome RDS is one of the most important causes of early neonatal morbidity and mortality. Cesarean delivery antenatl also a risk factor for the development of neonatal respiratory complications, including RDS. Respiratory failure in these babies occurs as a result of surfactant deficiency, antenatal steroids anatomical development of lung, as well as antenatal steroids in other organs. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of RDS. In this systematic review and bayer proviron dosage we evaluated the effectiveness of antenatal corticosteroids given at or after 34 weeks to reduce neonatal respiratory morbidity. Antenatal steroids review was performed according to a protocol designed a priori and recommended for systematic reviews.
To estimate whether antenatal corticosteroids given after fetal lung immaturity in pregnancies at 34 weeks of gestation or more would improve neonatal outcomes and, in particular, respiratory outcomes. We compared outcomes of neonates born at 34 weeks of gestation or more after fetal lung maturity testing: Primary outcomes were composites of neonatal and respiratory morbidity. Compared with corticosteroid-exposed neonates those born after mature amniocentesis had lower rates of adverse neonatal Administration of antenatal corticosteroids after immature fetal lung indices did not reduce respiratory morbidity in neonates born at 34 weeks of gestation or more.
Our study supports prolonging gestation until delivery is otherwise indicated. Although the administration of antenatal corticosteroids for the prevention of respiratory distress syndrome RDS in fetuses at less than 34 weeks of gestation is widely supported and practiced since the National Institutes of Health Consensus statement in , 1 , 2 little information exists on the use of antenatal steroids to promote fetal lung maturation in women at risk of preterm birth beyond 34 weeks of gestation.
The current recommendation of the American College of Obstetricians and Gynecologists is that elective delivery before 39 weeks of gestation should not be performed without documentation of fetal lung maturity. Still, with some evidence that steroid treatment after 34 weeks of gestation enhances fetal lung maturity profiles, 5 some obstetricians give antenatal corticosteroids after fetal lung testing is immature in an effort to induce overall fetal maturation and prevent neonatal morbidity with imminent delivery of the fetus.
When the obstetrician must make decisions based on immature fetal lung indices, three clinical pathways could be taken: Because fetal lung maturity testing predicts the absence of RDS, we hypothesized that corticosteroid-exposed newborns would have more respiratory morbidity but similar rates of other morbidities associated with prematurity. We also compared the corticosteroid-exposed neonates with a second reference group, whose mothers had immature fetal lung indices and were managed expectantly.
We hypothesized that neonates whose mothers were managed expectantly were likely more mature and therefore would have decreased incidence of neonatal morbidity. We performed a retrospective cohort study using a list of all women at 34 weeks of gestation or more who had amniocentesis for fetal lung maturity between January 1, , and July 15, , and subsequently delivered at Good Samaritan Hospital in Cincinnati, Ohio, the hospital with the largest delivery volume in the state.
We had previously screened the charts of most of these women for inclusion into a study powered to discern differences in adverse neonatal outcomes after documented fetal lung maturity 6 ; this study is a secondary analysis arising from that original study, including additional eligible women screened since February TDx-FLM II 55 mg or greater surfactant per gram albumin in the nondiabetic patient 70 mg or more surfactant per gram albumin in the diabetic patient , presence of phosphatidylglycerol, or lamellar body count more than 29, per microliter according to the standards of our laboratory.
In corticosteroid-exposed neonates, once fetal lung immaturity was noted, the mothers received antenatal corticosteroids, defined as any number of doses of either dexamethasone 6 mg or betamethasone 12 mg given before delivery.
To be included in the study group, women had to deliver within 1 week of their last steroid dose. Study exclusions were pregnancies complicated by congenital anomalies, chromosomal abnormalities, or multifetal gestation.
Women who delivered outside the study institution also were excluded. If women in the two reference groups received antenatal steroids at any point in pregnancy, they were excluded from the study because antenatal steroids were considered a potential confounder.
After approval by the Good Samaritan Hospital institutional review board, the charts of all women and their fetuses who met inclusion criteria were reviewed for the variables of interest.
The primary outcome was a composite measurement of respiratory morbidity, which included need for oxygen supplementation, continuous positive airway pressure, mechanical ventilation, or surfactant administration.
A second composite measurement for adverse neonatal morbidity was also examined, including admission to neonatal intensive care, need for ongoing respiratory support including oxygen, continuous positive airway pressure, or mechanical ventilation , surfactant administration, hypoglycemia requiring intravenous infusion, treatment with antibiotics for presumed sepsis, gavage feeding, or treatment for hyperbilirubinemia with phototherapy.
These neonatal outcomes were combined for a composite adverse outcome because they are common morbidities seen in the late preterm and early-term population 7 — 9 and require a higher level of monitoring or follow-up than for the healthy, uncomplicated newborns.
Pregnancy complications included hypertensive disease chronic, gestational or preeclampsia , diabetes pre-existing or gestational , premature rupture of membranes, oligohydramnios, preterm labor, or antenatal hospitalization for pregnancy complications. The data were analyzed using SAS 9. Backward selection yielded a final model of statistically influential and biologically plausible covariates. Adjusted analyses were not performed for individual morbidities as a result of their low frequency, less than 10 observations per category for most outcomes.
Of the charts screened of women who had amniocenteses for fetal lung maturity testing during the study period, pregnant women met inclusion criteria and had been treated with antenatal corticosteroids after immature fetal lung indices Fig. A mean period of 3. Seventy-six women had immature fetal lung indices and were managed expectantly, delivering within One hundred eighty-four women had mature fetal lung indices and delivered within 1.
The most frequent reasons in all three groups for amniocentesis with subsequent fetal lung maturity testing were history of prior cesarean delivery with a classical incision When the reason for amniocentesis and fetal lung maturity testing was evaluated by study group, important differences could be seen Table 1 , as a greater proportion of elective deliveries were seen in the mature amniocentesis group.
The frequency of pregnancy complications such as hypertensive disease, diabetes, preterm labor, intrauterine growth restriction, and oligohydramnios was higher in the corticosteroid-treated group but did not differ significantly among the three groups Table 2.
Fewer women managed expectantly had cesarean deliveries. More women treated with antenatal corticosteroids after immature fetal lung indices had premature rupture of membranes. We compared the newborns of the women with immature lung indices who were treated with antenatal corticosteroids with the other two groups Table 3. One neonate who delivered at 38 weeks of gestation in the mature amniocentesis group required mechanical ventilation and surfactant administration.
The corticosteroid-exposed neonates were born at the earliest gestational age by 0. The corticosteroid-exposed neonates had significantly higher rates of both the composite adverse neonatal outcome and the composite respiratory outcome compared with the expectantly managed group. In addition, the corticosteroid-exposed neonates had approximately twice the rate of hypoglycemia, need for intravenous fluids for hypoglycemia, sepsis evaluation, and treatment with antibiotics for presumed sepsis.
Once immature fetal lung indices are documented, expectant management to delay delivery rather than immediate delivery after antenatal corticosteroids was protective for neonatal morbidities. Compared with corticosteroid-exposed neonates, the neonates born after expectant management had decreased risk for multiple neonatal morbidities Table 5 , including the composite adverse respiratory outcome, admission to neonatal intensive care, hypoglycemia, sepsis evaluation, treatment with antibiotics for suspected sepsis, and oxygen supplementation.
Few studies have examined the benefits of giving antenatal corticosteroids to women after 34 weeks of gestation to prevent RDS. Although the investigators found a significant difference in the rate of RDS between the treatment and control groups 1. Our study evaluates differences in neonatal morbidity depending on the clinical pathway chosen after an amniocentesis documenting immature fetal lung indices.
After immature amniocentesis, some physicians may consider their patient stable enough to await mature amniocentesis before delivery or to manage expectantly based on the maternal risks of prolonging pregnancy weighed against the neonatal risks of a possible premature delivery. As a secondary analysis with a small sample size, we had insufficient power to analyze individual differences between specific morbidities when comparing between groups.
However, when comparing the three groups, despite no differences in major maternal morbidities such as hypertensive disease, diabetes, oligohydramnios, and preterm labor, corticosteroid-exposed neonates had higher rates of composite adverse neonatal outcome and composite adverse respiratory outcome compared with neonates born after mature amniocentesis or expectant management.
Even when we attempted to account for the differences in maternal and fetal factors such as presence of labor before delivery, intrauterine growth restriction, and premature rupture of membranes through multivariable adjusted analyses, we continued to see significantly higher rates of both composite outcomes and individual neonatal morbidities in the corticosteroid-exposed group compared with the other two groups.
Not only does steroid administration appear to have no benefit when administered in the late pre-term and early term period, but our findings suggest it may actually be harmful. Specifically, our study indicates an almost twofold increased risk of hypoglycemia and a threefold increased risk of sepsis evaluation for neonates whose mothers received corticosteroids at 34 weeks of gestation or more after immature amniocentesis compared with those managed expectantly.
Considering the biologic plausibility of steroids altering glycemic profiles and response to infection, these findings are certainly provocative, hypothesis-generating, and worthy of further evaluation in larger, randomized trials.
The retrospective nature of our study also may introduce bias based on inherent differences among pregnancies in which one approach was chosen over another. Performance of lung maturity amniocentesis implies that the health care provider considered the clinical scenario elective, because the health care provider had time to ponder and then act on the results. For example, a physician may desire sooner delivery in more complicated pregnancies but be willing to await mature amniocentesis or simply follow the pregnancy expectantly in those who have a more elective reason for delivery planning.
Pregnancies that are allowed to continue may be inherently different, possibly at lower risk for adverse outcome, than those in which the obstetric provider chooses to administer steroids after immature lung studies and then deliver in less than 1 week. These differences in reasons for amniocentesis testing may influence the frequency of morbidities, ie, those at highest risk needing imminent delivery may be in the corticosteroid-exposed group.
Although one can never completely account for all potential confounders in a cohort study such as this, we did adjust for important factors, which are known to influence neonatal outcome such as medical comorbidities, labor onset before delivery, and pregnancy complications such as intrauterine growth restriction and prolonged rupture of membranes.
After taking these factors into account, corticosteroid exposure seems to have no benefit and may possibly be harmful to neonates born at 34 weeks of gestation or more after immature amniocentesis. Our data suggest that the choice of steroid administration and then delivery if the results are immature are associated with high rates of adverse neonatal outcomes and that if the delivery is not otherwise medically indicated, either expectant management or delivery after mature fetal lung indices may be the prudent approach.
Antenatal corticosteroids have proven benefits in neonates born less than 34 weeks of gestation, 14 , 15 and these incurred benefits certainly outweigh any theoretic maternal or neonatal risks at that gestational age.
For neonates born at 34 weeks of gestation and greater, who still may have risk of neonatal morbidity as a result of prematurity, but much lower risk of more devastating morbidity such as intraventricular hemorrhage, the risks of corticosteroid administration may exceed the benefits. Our findings agree with recent cohort studies showing that the benefit of antenatal corticosteroids varies for neonates born at either extreme of gestation and incurs the greatest benefit for neonates born between 29 to 34 weeks of gestation.
Our work continues to support the notion that gestational maturity itself has the strongest correlation with a lack of neonatal morbidity. If delivery is able to be prolonged without undue risk to the mother, our study suggests that gestational maturity will decrease risk of subsequent neonatal morbidity. National Center for Biotechnology Information , U. Author manuscript; available in PMC Mar The publisher's final edited version of this article is available at Obstet Gynecol. See other articles in PMC that cite the published article.
Abstract OBJECTIVE To estimate whether antenatal corticosteroids given after fetal lung immaturity in pregnancies at 34 weeks of gestation or more would improve neonatal outcomes and, in particular, respiratory outcomes. RESULTS Of the charts screened of women who had amniocenteses for fetal lung maturity testing during the study period, pregnant women met inclusion criteria and had been treated with antenatal corticosteroids after immature fetal lung indices Fig.
Open in a separate window. Flow of study population Kamath-Rayne. NICU, neonatal intensive care unit. Footnotes Financial Disclosure The authors did not report any potential conflicts of interest. Effect of corticosteroids for fetal maturation on perinatal outcomes. Am J Obstet Gynecol. Timing of indicated late-preterm and early-term birth.
American College of Obstetricians and Gynecologists. Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles. Neonatal morbidity after documented fetal lung maturity in late preterm and early term infants.
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