Evaluate the importance of giving antenatal corticosteroids in respiratory distress syndrome in preterm neonates

After completing this article, readers should be able to: 1. Describe the rationale for the use of antenatal corticosteroids for human fetal maturation. 2. Delineate recommendations of the 1994 National Institutes of Health Consensus Conference on Antenatal Corticosteroids. 3. Review areas of controversy in the clinical use of antenatal corticosteroids. 4. Describe the potential risks of multiple courses of antenatal corticosteroids. 5. Delineate current recommendations for clinical use of antenatal corticosteroids to promote fetal maturation. Glucocorticoid administration initially was appreciated as a method for accelerating development of the intestine more than 40 years ago. Since that time, developmental effects of these agents have been defined in at least 16 tissues of mammals. More than 30 years ago, while studying the mechanism of initiation of labor in sheep, Liggins made the observation that infusion of corticosteroids into fetal lambs was associated with improved survival and decreased lung disease in animals delivered preterm. Subsequently, numerous studies in cell culture, animal models, and human fetal tissue have delineated the multiple effects of glucocorticoids on the developing lung. These include increases in both the total tissue and alveolar surfactant pools; a decrease in vascular permeability, with less protein leak into the alveolar spaces; enhanced clearance of lung water; maturation of parenchymal structure; increase in lung compliance and maximal lung volume; enhanced response to surfactant treatment; and improvement in respiratory function, outcome, and survival. (See accompanying article on scientific rationale for use of antenatal glucocorticoids.) In 1972, the first randomized clinical trial of administration of antenatal corticosteroids (ANCS) in humans demonstrated decreased mortality and a decreased incidence of respiratory distress syndrome (RDS) in preterm infants born at less than 34 weeks’ gestation, who were treated with betamethasone for at least 24 hours before delivery. Over the ensuing 20 years, multiple clinical investigations continued to document the effectiveness of ANCS on …

Introduction: The management of women with pregnancy complications at the peri-viability period involves a complex set of medical, ethical, emotional, and social challenges for the obstetrician. The survival rate of preterm babies has been improving along with advancement in neonatal intensive care unit (NICU) technology. Our recent experience has shown survival of even very preterm infants with the use of surfactant therapy. Objective: This observational study was conducted in order to evaluate the survival benefit of surfactant therapy on preterm neonates, to enable straight forward decisions to be taken by the obstetricians regarding antenatal steroid prophylaxis, in-utero transfer and mode of delivery in case of inevitable preterm births. Material and Methods: This study was conducted in the NICU of a tertiary hospital over a period of 3 years (2009-2011). We recruited only those preterm neonates who received surfactant therapy and the records were obtained and analyzed. Survival benefits of surfactant therapy, role of antenatal steroids, in utero transfer and mode of delivery were studied. Results: Almost all (98.6%) neonates who did not receive antenatal steroids at all, landed up in respiratory distress syndrome (RDS) requiring surfactant therapy. Among the outborns 59.2% had an extended NICU stay as compared to 49.4% in the inborn group. The overall incidence of RDS was found to be more in caesarean delivery group (96.3%). However if the period of gestation at the time of delivery was less than 28 weeks, caesarean delivery had lesser incidence (12.5%) of RDS compared to vaginal delivery (27.1%). Similar finding was noted when comparing mortality. In less than 28 weeks gestation, when caesarean was done 2.5% newborn babies died, whereas in the vaginal delivery group 12.5% babies succumbed to death. Conclusion: 1) Even in centers with facilities of surfactant therapy, steroids prophylaxis should be considered before delivery 2) Obstetricians should practice in utero transfer, to centers with NICU, having availability and technical expertise of surfactant prophylaxis 3) With the availability and wide spread usage of surfactant for premature neonates caesarean delivery should not be deferred for fetal benefit. DOI: http://dx.doi.org/10.4038/sljog.v34i3.4882 Sri Lanka Journal of Obstetrics and Gynaecology 2012; 34: 99-105

Respiratory distress syndrome is a leading cause of neonatal intensive care unit admissions for late preterm (34-36 weeks gestational age) and term infants (37-41 weeks). The risk for respiratory morbidity appears to increase after an elective caesarean delivery and might be reduced after antenatal corticosteroids. However, before considering antenatal corticosteroids for women at high risk of preterm birth after 34 weeks, the incidence of respiratory distress syndrome and the effect of delivery mode on this incidence requires further evaluation. Therefore, this study aimed to investigate the relationship between respiratory distress syndrome incidence and delivery mode in late preterm and term infants. In this retrospective cohort study, the clinical databases of the University Hospitals of Zurich and Basel were queried regarding all live births between 34 + 0 and 41 + 6 weeks. Neonatal intensive care unit admissions due to respiratory distress syndrome were determined and analysed in regard to the following delivery modes: spontaneous vaginal, operative vaginal, elective caesarean, secondary caesarean and emergency caesarean. After excluding malformations (n = 889) and incomplete or inconclusive data (n = 383), 37,110 infants out of 38,382 were evaluated. Of these, 5.34% (n = 1980) were admitted to a neonatal intensive care unit for respiratory distress syndrome. Regardless of gestational age, respiratory distress syndrome in infants after spontaneous vaginal delivery was 2.92%; for operative vaginal delivery, it was 4.02%; after elective caesarean delivery it was 8.98%; following secondary caesarean delivery, it was 8.45%, and after an emergency caesarean it was 13.3%. The risk of respiratory distress syndrome was higher after an elective caesarean compared to spontaneous vaginal delivery, with an odds ratio (OR), adjusted for gestational age, of 2.31 (95% CI 1.49-3.56) at 34 weeks, OR 5.61 (95% CI 3.39-9.3) at 35 weeks, OR 1.5 (95% CI 0.95-2.38) at 36 weeks, OR 3.28 (95% CI 1.95-5.54) at 37 weeks and OR 2.51 (95% CI 1.65-3.81) at 38 weeks. At 39 weeks, there was no significant difference between the risk of respiratory distress syndrome after an elective caesarean vs. spontaneous vaginal delivery. Over the study period, gestational age at elective caesarean delivery remained stable at 39.3 ± 1.65 weeks. The incidence of respiratory distress syndrome following an elective caesarean is up to threefold higher in infants born with less than 39 weeks gestational age compared to those born by spontaneous vaginal delivery. Therefore - and whenever possible - an elective caesarean delivery should be planned after 38 completed weeks to minimise the risk of respiratory morbidity in neonates.

1. Yvonne E. Vaucher, MD, MPH* 1. *Clinical Professor of Pediatrics, Division of Neonatology, University of California, San Diego, Calif. After completing this article, readers should be able to: 1. Describe the most common cause of chronic lung disease during infancy. 2. Explain the importance of a history of bronchopulmonary dysplasia throughout childhood. 3. Identify infants at high risk for developing bronchopulmonary dysplasia. 4. List the adverse effects associated with postnatal corticosteroids. Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmonary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive care units and their caretakers. BPD is the most common cause of chronic respiratory disease during infancy and remains a major cause of long-term medical, pulmonary, and neurodevelopmental morbidity, increasing the cost of health care and the utilization of medical and educational resources throughout childhood. BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after birth and accompanied by characteristic radiographic findings that correspond to anatomic abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical presentation has evolved over the past 30 years, so has the definition. As originally described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive radiographic changes in preterm infants who were treated for severe respiratory distress syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen dependence. This form of BPD occurred in larger, relatively mature preterm infants, who required treatment with high-pressure mechanical ventilation and high concentrations of oxygen. Although the acute respiratory disease initially improved in these infants, oxygen requirements increased 7 to 10 days after birth and persisted for at least 28 days. The definition of BPD subsequently was modified by Bancalari to include preterm infants who had less severe RDS that initially required short-term mechanical ventilation, but who also developed persistent respiratory symptoms and an oxygen requirement for at least 28 days after birth …

Antenatal corticosteroids administration on mortality and morbidity in premature twins born at 25∼34 gestational weeks: A retrospective multicenter study

After completing this article, readers should be able to: 1. Describe the standard of care for prenatal corticosteroids for women in preterm labor prior to 34 weeks’ gestation. 2. Describe the effects of prenatal corticosteroids on the fetus. 3. List the preferred corticosteroid for prenatal treatments. 4. Explain the recommendation regarding not using repetitive courses of prenatal corticosteroids. Prenatal glucocorticoids are standard of care for women at high risk of preterm delivery prior to 34 weeks’ gestation because randomized, controlled trials and extensive meta-analyses demonstrate decreased death and improved outcomes, primarily related to less respiratory distress syndrome (RDS) and a decreased incidence of intraventricular hemorrhages (IVH) (Fig. 1). (1) However, it is worth remembering that the benefits of prenatal corticosteroids initially were demonstrated in 1972, and most of the trials were completed before 1985. Most infants in the trials were delivered after 28 weeks’ gestation and in the presurfactant era, when mortality rates for infants whose birthweights were less than 1 kg were high and when obstetric management differed from current practice. Maternal corticosteroid therapy is validated practice, but care strategies proven to be effective may lose effectiveness as other aspects of care change and the target population most likely to benefit changes. This review asks a series of questions to frame the overriding question of how antenatal corticosteroids should be used in 2006. Figure 1. Meta-analysis of randomized controlled trials of prenatal corticosteroids. Adapted from Crowley. (1) The current recommendations come from the 1994 National Institutes of Health (NIH) Consensus Conference and were reinforced by a second NIH Consensus Conference in 2000. (2) The key points from the guidelines are: 1. The benefits of prenatal corticosteroids outweigh any risks that have been identified. The benefits include decreased death and decreased incidence of RDS and IVH. 2. All fetuses at 24 to 34 weeks’ gestation are candidates …

Antenatal corticosteroid (ACS) treatment is widely used for the prevention of respiratory distress syndrome (RDS) in preterm infants. However, the efficacy and safety of ACS treatment remains controversial in twin pregnancies. To investigate the effect of ACS therapy, single or multiple courses, on the incidence of neonatal RDS in singleton and twin pregnancies. We retrospectively evaluated the pregnancy and neonatal outcomes of 450 singleton and 117 twin pregnancies delivered at 24-34 weeks of gestation due to preterm labour or preterm premature rupture of membranes. The subjects were categorised into four groups according to ACS exposure: 0, 1, 2 and > or = 3 courses. Overall, RDS occurred more frequently in twins compared to singletons (41.0% vs 25.3%, P < 0.001). In singleton pregnancy, the incidence of RDS was significantly lower in the ACS user groups than in the non-user group, with the lowest incidence in the multiple course groups. An increase in the number of courses of ACS was associated with a reduction in the incidence of RDS (odds ratio 0.349, 95% confidence interval 0.226, 0.537, P < 0.001) independent of confounding variables. In twin pregnancies, however, the incidence of RDS was not significantly different in comparisons among the four groups. Multiple courses of ACS were associated with a significantly decreased risk of RDS in singleton pregnancies. However, the current standard dose or interval for ACS administration in singleton pregnancy, as either a single or multiple courses, did not reduce RDS in twins.

Background: Premature infants have a higher incidence of respiratory distress syndrome (RDS), which is one of the main causes of early neonatal mortality. Objectives: The objective is to study the incidence and outcome of RDS in preterm babies <34 weeks of gestation born to mothers who had received antenatal corticosteroids (ACS). Methodology: A prospective observational study was conducted among preterm babies from January 2015 to December 2015 in a tertiary care hospital of South India. Details of the mothers with a period of gestation 34 weeks or less who had received ACS were recorded. Results: The study population included 749 preterm babies (<34 weeks) delivered in our hospital. Among them, 698 (93.2%) mothers received two doses of ACS and 51 (6.8%) received only a single dose of ACS. Neonates whose mothers received two doses of ACS had a significantly lower incidence of RDS (27.6% vs. 100%, p<0.001), lower rate of mechanical ventilation (45% vs. 72.5%, p<0.001), and higher survival rate (87% vs. 68.6%, p=0.001) than neonates whose mothers received a single dose of ACS. The occurrence of RDS is highest in 26

One of the most frequent causes of neonatal mortality or NICU admission of neonates especially in premature infants is Neonatal Respiratory Distress Syndrome (NRDS). Antenatal steroids are the most important and widely utilized interventions for improvement of neonatal outcomes like reducing incidence of respiratory distress syndrome (RDS), reducing neonatal NICU (neonatal intensive care unit) admission rates and also improve outcomes of pre-term infants. Antenatal steroids (ANS) like betamethasone 12 mg are given at 24 hourly IM at 28-34 weeks of gestation to mother. For administration of corticosteroids at less than 24 weeks of gestational age decision should be made at a senior level by taking all clinical aspects into consideration.To observe the effect of Betamethasone administration IM in pregnant women at risk of pre-term delivery and fetal outcomes in terms of development of Respiratory Distress Syndrome (RDS) and Neonatal Intensive Care Unit (NICU) admission rate by giving it between 28 to 34 weeks of gestation.Antenatal corticosteroids (betamethasone) play an important role for prevention of respiratory distress syndrome and reducing NICU admission rate of new borns and also reduce neonatal mortality and morbidity but benefits related to the time between administration of corticosteroid and delivery needed to be explored. Benefits of the injection betamethasone administration IM 12 mg between 24 hours and seven days on pre-term delivery has been established.,This was prospective study conducted in private setup from November 2020 to March 2021 in Scientific Research Institute, Surendranagar, Gujarat, India. Study comprised of 100 women with single tone pregnancies (28 – 36 weeks gestational age) in age group of 19 – 33 years not in labour, but at risk for pre-term delivery based on fetal or maternal indications. These pregnant women were treated with two doses of 12 mg Betamethasone Intramuscularly apart of 24 hourly for maturation of fetal lungs.Antenatal corticosteroids like betamethasone have a significant benefit on neonatal outcome even if used after 34 weeks of pregnancy. This was given prophylactically to those who are known to have increased risk of pre-term labour. Antenatal steroid like betamethasone 12 mg IM is also of benefit to reduce neonatal respiratory distress syndrome (NRDS) and NICU admission rates by giving it at 28-34 weeks of gestational age.

Background: Late preterm birth is associated with increased risks of adverse neonatal outcomes, including respiratory distress syndrome (RDS) and hypoglycemia. The use of antenatal corticosteroids (ACS) has been shown to reduce these risks in early preterm infants. However, the efficacy of rescue ACS in late preterm infants remains uncertain. This study aimed to assess the effectiveness of rescue ACS in reducing the incidence of RDS and hypoglycemia in late preterm infants. Methods: A retrospective cohort study was conducted on women who delivered singleton late preterm infants (34 + 0 to 36 + 6 weeks of gestation) at a tertiary hospital. The inclusion criteria were completion of the initial cycle of ACS in the early preterm period (before 34 + 0 weeks of gestation). Data on maternal baseline characteristics, ACS administration, and neonatal outcomes were collected from medical records. Statistical analyses, including logistic regression and multivariate modeling, were performed to assess the association between rescue ACS and neonatal outcomes. Results: A total of 155 singleton late preterm infants were included in the study. Among them, 27.8% (43/155) received rescue ACS after 34 weeks of gestation, while 72.2% (112/155) did not. Neonates who did not receive rescue ACS had a significantly higher incidence of RDS compared to those who did (10.7% vs. 0%, p = 0.038). However, the results were not statistically significant in the multivariate analysis (odds ratio (OR), 0.07; 95% confidence interval (CI), 0.00–1.48; p = 0.087). Additionally, there were no significant differences in the frequencies of hypoglycemia (glucose level ≤40 mg/dL) (8.0% vs. 9.3%, p = 0.755) and hypoglycemia (glucose level ≤60 mg/dL) (52.7% vs. 37.2%, p = 0.106) between the two groups. Conclusions: Rescue ACS administration in late preterm infants was not associated with a reduced risk of RDS. Additionally, there was no significant difference in the incidence of hypoglycemia. Further studies with larger sample sizes are needed to confirm these results and assess potential long-term implications.

It is nearly 25 years since Liggins and Howie first reported the maturational benefits of antenatal corticosteroids given to mothers of preterm infants.1 They reported reduced incidence of respiratory distress...

Objective: To assess the impact of antenatal corticosteroids (ACS) therapy on mortality and morbidities in small for gestational age (SGA) preterm infants. Method: A retrospective database analysis was performed. Preterm infants born at 24-34 completed weeks who were diagnosed as SGA in 14 hospitals in China between 2013 and 2014 were evaluated for mortality and major morbidities including respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotising enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis. These cases were classified into two groups: ACS group and non-ACS group (NACS). Multivariate logistic regression analysis was performed to assess the effect of ACS on neonatal mortality and morbidities. Result: Among the 6 437 infants born at 24-34 completed weeks, 602 were SGA(9.4%), and ACS was administered to 3 432 infants (53.3%). Among SGA infants at gestational age (GA) of 24-31 completed weeks, ACS treatment were associated with decreased mortality (16.9%(13/77) vs. 32.1%(17/53), χ(2)=4.082, P<0.05), incidence of RDS (48.1%(37/77) vs. 79.2%(42/53), χ(2)=12.183, P<0.05) and incidence of severe RDS (33.8%(26/77) vs. 55.6%(30/53), χ(2)=6.677, P<0.05). The incidence of IVH was higher in ACS group than that in NACS group (10.9%(27/248) vs. 5.8%(13/224), χ(2)=3.921, P<0.05) among 32-34 completed weeks infants. There were no significant differences between the ACS group and the NACS group in the incidence of BPD, NEC, ROP, PDA and sepsis (P all >0.05). Multivariate logistic regression analysis demonstrated a decreased mortality (OR=0.375, 95% confidence interval (CI): 0.188-0.749, P=0.005)and incidence of RDS (OR=0.697, 95% CI: 0.462-0.953, P=0.041) in SGA infants exposed to antenatal steroids. There were no significant differences in BPD, IVH, NEC, ROP, PDA and sepsis risks in ACS group compared with NACS group (P all >0.05). Conclusion: ACS administration could reduce the mortality and major morbidities in SGA preterm infants less than 32 weeks GA. This study suggests that ACS should be given to growth restricted fetuses at risk of preterm delivery in order to improve perinatal outcome.

The primary aims of this study were to investigate if exposure to antenatal corticosteroids (ACS) was associated with lower rates of perinatal mortality (primary outcome) and other adverse perinatal outcomes (i.e., stillbirth, early neonatal mortality, APGAR score of < 7 at 5 mins, neonatal sepsis and respiratory distress syndrome) in preterm infants in hospitals in Tanzania. We also examine factors associated with administration of ACS among women at risk of preterm delivery. A hospital-based prospective chart review study was undertaken in four hospitals located in Nyamagana and Sengerema districts, Tanzania. The study population included all stillborn and live born preterm infants delivered between 24 to 34 weeks of gestation between July 2019 to February 2020. A total 1125 preterm infants were delivered by 1008 women (895 singletons, 230 multiple). Sociodemographic and medical data were recorded from participants' medical records. Three hundred and fifty-six (35.3%) women were administered at least one dose of ACS between 24 to 34 weeks' gestation and 385 (34.2%) infants were exposed to ACS. Infants exposed to ACS had a lower rate of perinatal mortality (13.77%) compared to those who were not exposed (28.38%). Multivariate analysis indicated that infants exposed to ACS were less likely to die during perinatal period, aRR 0.34 (95%CI 0.26-0.44). Only one-third of the sample was provided with ACS. Administration of ACS was associated with maternal education, attending antenatal care more than 3 times, method used to assess gestational age, maternal infection, exposure to maternal antibiotics, delivery mode and level of health facility. ACS significantly reduced the risk in perinatal mortality among infants born preterm in a limited resource setting. However, only about one-third of eligible women were provided with ACS, indicating low usage of ACS. Numerous factors were associated with low usage of ACS in this setting.

Objective To discuss the case distribution and the influencing factors of mortality of late preterm infants with hypoxemic respiratory failure in middle and east of Shandong province. And to provide a theoretical basis for the improvement of the level of clinical diagnosis and treatment in late preterm infants with respiratory failure and provide reference evidence for the related researches in Shandong province and even the whole country. Methods Two hundred and sixteen late preterm infants with respiratory failure were selected as the study objects to carry out prospective trial by cluster sampling from 7 hospitals of the middle and east of Shandong province from Jan 1, 2010 to Dec 31, 2012. The basic information, primary disease, clinical diagnosis and treatment methods, clinical outcome, mortality and influencing factors were analyzed. Results (1) All 216 investigation questionnaires were received. The ratio of male to female was 1.3∶1. The pathogenesis that leaded to the incidence of respiratory diseases were not identical in various places. (2) Mean birth weight was (2 660±686) g, the minimum birth weight was 1 900 g and the maximum birth weight was 3 600 g. There were 38 cases with congenital anomalies, including 6 cases with 2 or more kinds of malformation, and congenital heart disease (including patent ductus arteriosus) was 16 cases. Mean age of mothers with respiratory failure infants was 32 years, the minimum one was 18 years and the maximum one was 42 years. The overall cesarean section rate was same to the one of spontaneous labor (106 cases vs 110 cases). One hundred and thirty-seven cases with acute respiratory failure received antenatal steroids. (3) The main primary diseases of infants with respiratory failure were respiratory distress syndrome (112 cases), pulmonary infection and sepsis (52 cases). The complications were, in turn, pulmonary infection and sepsis (23 cases), patent ductus arteriosus (89 cases) and vital organs hemorrhage (7 cases). (4) The case fatality rate of infants within 34 to 35 weeks and 35 to 36 weeks were 10.2% and 8.7% respectively, which were significantly higher than those of infants within 36 to 37 weeks (χ2=157.148, P=0.000). (5) Congenital malformation [OR=2.063, 95%CI (1.297, 3.264)], low birth weight [OR=4.335, 95%CI (1.636, 11.497)], vital organs hemorrhage[OR=4.598, 95%CI (1.370, 14.925)] and mechanical ventilation alone [OR=0.531, 95%CI (0.314, 0.902)] linked to higher risk of death after respiratory failure for the late preterm infants. Conclusion At present, respiratory failure caused by various diseases occurred at low frequencies in the middle and east of Shandong province. The primary diseases are respiratory distress syndrome, pulmonary infection, and severe asphyxia. It takes more time to treat the late preterm infants with respiratory distress and the prognosis can be improved by a variety of treatments. Key words: Late preterm infant; Respiratory failure; Epidemiology

After completing this article, readers should be able to: Few aspects of neonatal care have generated as much controversy as the assessment of blood pressure (BP) and need for treatment of perceived abnormalities of this physiologic variable. Familiarity with clinical situations in which BP may be low should allow anticipation of this common clinical problem and timely intervention when such treatment is necessary (Tables 1 and 2). In this article, we review factors that have been shown to have the greatest effect on BP.A direct reading from an indwelling arterial catheter represents the “gold standard” for measuring BP in the neonate, and this method should be used whenever possible. Obviously, arterial access may not always be available, and the ability to monitor BP noninvasively using an oscillometric technique represents a major advancement in neonatal care. The correlation between direct and indirect methods generally has been good. Disparities in results have been related to various factors, including inappropriate cuff width-to-arm ratio or problems with the arterial catheter-transducer system, such as air bubbles or clots. In general, indirect determinations are higher than those obtained directly, often by 3 to 5 mm Hg.The individual contributions of birthweight and gestational age to BP are difficult to delineate. Several groups of investigators have shown that BP at birth is higher in larger, more mature infants. There is evidence that small-for-gestational age infants have lower BPs than do larger babies of comparable gestational age, which suggests that birthweight per se may be more than a marker for increased maturity.Early studies involving large numbers of infants who had a wide range of birthweights and gestational ages demonstrated the significance of both of these variables. In a recent report of a large multicenter study conducted by the Philadelphia Neonatal Blood Pressure Study Group, systolic and diastolic blood pressures were significantly correlated with birthweight (Fig. 1) and gestational age (Fig. 2).Le Flore and associates studied 116 very low-birthweight (VLBW) neonates during the first 72 hours after birth. Following multiple linear regression, both gestational age and birthweight were primary variables predicting mean blood pressure (MBP) during this period. However, gestational age explained more of the variance in MBP during the first 24 hours, with each additional week of gestation increasing MBP by 1.4 mm Hg. Neonates of 24 to 25 weeks’ gestation had an initial MBP of 27±4 mm Hg versus 39±7 mm Hg for neonates at 32 to 33 weeks’ gestation (P≤0.01) (Fig. 3). In contrast, birthweight explained more of the variance in MBP between 25 hours and 72 hours after birth, with each increase of 100 g associated with an increase in MBP of 1.0 mm Hg. The Joint Working Group of the British Association of Perinatal Medicine has recommended that MBP (in mm Hg) be maintained at or above the gestational age of the infant (in weeks). Further investigation is required to establish the safety and efficacy of this approach.As alluded to previously (Fig. 3), MBP increases postnatally in VLBW neonates regardless of gestational age. Zubrow and associates found a similar relationship between BP and postnatal age in infants whose birthweights were 750 to 4,000 g and gestational ages were 22 to 42 weeks (Fig. 4). When the effect of postnatal age on BP was analyzed over a longer period of time, systolic BP was approximately 30 mm Hg higher at the 4-month age-adjusted outpatient examination compared with values at 7 days after birth.The association between advancing birthweight, gestational age, and postnatal age and increases in BP is not understood completely. A discussion of the complex neural, hormonal, and vascular mechanisms that control BP is beyond the scope of this article, but their maturation is a significant consideration. Anatomic relationships may play a role, and decreases in right ventricular pressure after birth may result in improved left ventricular shape and function. Also, it has been shown that urinary prostaglandin E2 and plasma 6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) decrease during the first 3 postnatal days in preterm neonates. This could result in a rise in vascular tone and increased vascular reactivity. More recently, it has been reported that vascular smooth muscle protein expression and contractility demonstrate functional maturation during development. Thus, the rise in BP during the fetal-neonatal transition may reflect decreases in the activity and synthesis of vasodilators, which are critical to fetal survival, as well as intrinsic changes in vascular smooth muscle function occurring prior to and following birth, both of which appear to be developmentally regulated.Significant hypotension in the neonate can be a reflection of prenatal, intrapartum, or postnatal hemorrhage (Table 1). Fetomaternal, twin-twin, intracranial, subgaleal, and hepatic hemorrhages are the most common types of significant blood loss. Adrenal hemorrhage is a very rare (but reported) cause of severe neonatal hypotension, although the mechanism of subsequent blood pressure instability may be more associated with adrenocortical derangement than significant blood loss. Hemorrhage should be considered in any hypotensive neonate, but it is important to note that the initial physiologic response involves the release of vasoactive substances, such as catecholamines and arginine vasopressin. Hypotension may be a relatively late finding that suggests the presence of acute blood loss. The pre-equilibration hemoglobin and hematocrit values also may be misleading following blood loss.Infusion of cortisol into the sheep fetus results in increased arterial pressure. Several reports have suggested that neonatal BP is higher in preterm infants whose mothers received antenatal steroids to hasten fetal lung maturity. This finding would not be unexpected because previous studies have suggested that sick preterm neonates may have relative adrenocorticosteroid insufficiency. Furthermore, successful treatment with hydrocortisone or dexamethasone, administered because of hypotension refractory to conventional therapies, has been documented.In one study, neonates whose mothers received dexamethasone had higher MBPs during the first 3 days after birth, but this relationship was less clear when adjustment for birthweight was made. After this adjustment, a significant difference in BP was noted only 2 hours following initial treatment with exogenous surfactant. A subsequent study investigated the amount of BP support required by extremely preterm infants (23 to 27 weeks’ gestation) whose mothers did or did not receive antenatal steroids. Infants not exposed to antenatal steroids had lower MBPs from 16 to 48 hours after birth. Furthermore, the use of dopamine was increased in the infants not exposed to antenatal steroids. The reduction in severe intraventricular hemorrhage observed in infants whose mothers received antenatal steroids has been linked to normal BP in those infants. In another study, MBP during the first 24 hours after birth was increased in VLBW infants whose mothers received antenatal steroids, and volume expansion and vasopressor support were decreased in those infants.Conversely, LeFlore and associates reported no differences in BPs among 116 VLBW neonates whose mothers did or did not receive antenatal steroids, and similar results were obtained in another study. Other investigators have reported a tendency for higher mean BP in infants weighing at least 1,000 g whose mothers received antenatal steroids but a tendency for lower MBP in infants weighing less than 1,000 g who were exposed to antenatal steroids. Leviton and colleagues found no difference in the incidence of lowest MBP less than 30 mm Hg in infants whose mothers did or did not receive a complete course of antenatal glucocorticoid prophylaxis.Obviously, further investigation is required to determine the relationship between antenatal steroids and BP. Perhaps in the subset of preterm infants who truly have relative adrenal insufficiency, antenatal steroids may enhance neonatal cardiovascular stability and raise BP, while antenatal steroids have little or no effect on BP in those who have adequate adrenal function.The effect of route of delivery on BP in the neonate has been studied extensively. Several studies in term neonates have indicated that BP in vaginally delivered infants is higher than in those delivered by cesarean section. In general, these studies have attributed the higher BP in the former group to increased catecholamine concentrations and cord blood arginine vasopressin and adrenocorticotropin hormone levels. However, among VLBW infants, blood pressures were similar in infants delivered vaginally and those delivered by cesarean section. Likewise, in the study by Zubrow and associates, which included 106 infants of 32 weeks’ gestational age or younger, stepwise multiple linear regression analysis did not identify route of delivery as a significant determinant of BP variation. Breech delivery has been associated with BP in the lower range of normal. The volume of placental transfusion (as well as postnatal transfusion) also may affect BP.The classic studies of Dawes in newborn monkeys demonstrated that BP initially rises with ongoing asphyxia, but after 5 minutes, it decreases progressively. As emphasized by the American Academy of Pediatrics/American Heart Association Committee on Neonatal Resuscitation, many infants who have birth depression and possibly some degree of hypotension respond to effective positive-pressure ventilation and do not require specific measures to raise BP (see accompanying article on treatment of hypotension).Circulatory changes resulting from apnea in the neonate have been summarized by Miller and Martin. The initial decrease in heart rate is accompanied by a rise in pulse pressure, usually due to an increase in systolic pressure. These events presumably result from increased filling volume associated with bradycardia, which leads to enhanced stroke volume in accordance with Starling’s law. As the severity of apnea and bradycardia increases, BP may decrease, along with a fall in cerebral blood flow velocity. Thus, during prolonged apnea, cerebral perfusion may decrease significantly, placing the infant at risk for brain injury.Infants who have severe respiratory distress syndrome (RDS) may have lower BPs than those observed in healthy preterm neonates or infants who have less severe RDS. An association in infants who have RDS between marked fluctuations in arterial BP and fluctuating cerebral blood-flow velocity has been demonstrated. Also, an association has been reported between acute hypocarbia and marked systemic hypotension.Three aspects of respiratory management in preterm neonates have been shown to affect BP: 1) use of increased airway pressures, given either by constant positive airway pressure (CPAP) or intermittent mandatory ventilation; 2) suctioning of the airway, occasionally accompanied by a fall in diastolic pressure; and 3) instillation of an exogenous surfactant preparation into the airway. Although a number of studies in animals and humans have shown no effect of positive end-expiratory pressure or CPAP on BP, Kluckow and Evans observed a highly significant negative influence of mean airway pressure on MBP in preterm neonates requiring mechanical ventilation. BP fluctuations during mechanical ventilation may be decreased through the use of various methods of synchronized mechanical ventilation.Perlman and Volpe measured arterial BP, cerebral blood-flow velocity, and intracranial pressure in 35 intubated preterm neonates undergoing routine suctioning. MBP increased during suctioning in all but one patient, and these investigators concluded that the observed increases in cerebral blood-flow velocity and intracranial pressure were directly related to the increased blood pressure. Perry and colleagues reported an association between systolic BP above a “stability boundary” and increased periventricular-intraventricular hemorrhage, with BP elevations related temporally to suctioning. In addition to suctioning, BP response to various care procedures, including chest auscultation and physiotherapy, mouth rinsing, diaper changing, and nasogastric feeding, have been studied, and in general, BP responses were biphasic, with a decrease in BP followed by a greater and longer lasting increase.Numerous investigators have studied the physiologic effects of surfactant instillation in neonates, and differences in these reports may be due to dosing or technique of administration. In most studies, any effects on BP were transient. There may be greater hemodynamic effects associated with natural surfactant preparations, perhaps related to their generally more rapid pulmonary effects compared with artificial surfactant preparations.Studies of patent ductus arteriosus (PDA) in animals and preterm human neonates generally have shown significant decreases in diastolic BP. In one study, investigators noted that a diastolic BP of less than 28 mm Hg suggested the presence of PDA, although it is apparent from numerous studies that many normal VLBW neonates actually have mean BPs lower than 28 mm Hg.Among infants whose birthweights were 1,000 to 1,500 g, Evans and Moorcraft found similar BPs in the PDA and nonPDA groups. However, in those whose birthweights were less than 1,000 g, mean systolic and diastolic BPs were lower in infants who had PDA compared with those who did not. Furthermore, these hemodynanic effects could be demonstrated well before the PDA became clinically apparent. These authors cautioned against the use of volume expanders or inotopic agents in this population because these treatments might be counterproductive if the cause of the hypotension is a hemodynamically significant but clinically silent PDA. Furthermore, volume expansion appears to be a risk factor for the development of symptomatic PDA in VLBW neonates. It is apparent that problems with low BP related to PDA, especially diastolic BP, may result in inadequate perfusion of vital organs because of the “vascular steal” phenomenon. Optimum management of this clinical problem, of course, is directed at closure of the PDA rather than increasing the BP by other means.Neonatal sepsis is a common problem that can be devastating in both preterm and term neonates. The complicated pathophysiology of neonatal sepsis involves activation or release of numerous inflammatory and vasoactive substances, and hypotension can be a relatively late finding. The resulting effect on the cardiovascular system can be vasoconstriction, as is seen frequently in term and postterm septic neonates who have pulmonary hypertension or peripheral vasodilation with accompanying cardiomyopathy resulting in profound systemic hypotension (see accompanying article on treatment of hypotension). Necrotizing enterocolitis, which often accompanies sepsis, continues to be a common problem in the neonatal intensive care unit, and neonates who have moderate-to-severe disease very frequently are hypotensive.Maternal smoking may be associated with increases in both systolic and diastolic BP in the neonate, and a direct relationship between neonatal BP and the number of cigarettes smoked has been shown. This effect may persist for at least 12 months. Although maternal hypertension may be a factor associated with higher neonatal BP, this is not reported consistently. Cocaine exposure in utero has been shown to be associated with increased BP on the first day after birth in term neonates, and increased circulating catecholamine concentrations have been demonstrated. Mean arterial pressure was unchanged, but arterial pressure variability was decreased with both pancuronium and pethidine (meperidine). Fentanyl and midazolam may cause hypotension in neonates. Numerous studies have demonstrated that BP may increase and decrease with pneumothorax. Seizure activity may have variable effects on blood pressure. Increased neonatal BP has been documented in infants who have chronic lung disease and receive dexamethasone therapy.The smallest, least mature infants have lower BPs than infants who are larger and more mature. The effect of antenatal steroids, given to the mother when preterm delivery is anticipated, is controversial. Maternal smoking and route of delivery are perinatal factors that can influence neonatal BP. Sepsis and hemorrhage are associated with significant derangements in BP and always must be considered in a hypotensive neonate. PDA may be associated with a significant decrease in diastolic BP.