The effect of glucocorticoids on the maturation of premature lung membranes. Preventing the respiratory distress syndrome by glucocorticoids

The effect of glucocorticoid on the maturation of premature lung membranes was studied in 121 premature infants by administering variable dosages of Decadron to the 114 mothers prior to delivery. The results were compared with findings in a group of 390 infants born in the same hospital during this study. Administration of all three test doses, 8, 16, and 24 mg., significantly decreased the incidence of RDS in all gestational age and birth weight categories. For infants less than 32 weeks, the incidence was decreased from 75 to 46.2%; those 32 to 36 weeks, from 58 to 20.2%; and in those older than 36 weeks, from 24.4 to 0 per cent. The incidence in infants less than 1,000 grams was reduced from 100 to 71.5%; 1,000 to 1,500 grams, from 67.4 to 21.6%; 1,500 to 2,000 grams, from 52.3 to 22.6%; and in heavier than 2,000 grams, from 38.1 to 13.4%. The results also showed that glucocorticoid does not significantly reduce RDS if administered less than 24 hours prior to delivery. The incidence is reduced more than 50% if administered more than 24 hours prior to delivery.     

Results of conservative management of premature rupture of the membranes

The maternal and fetal outcome of a conservative management protocol, at a tertiary care center, for premature rupture of membranes between 25 and 34 weeks' gestation was reviewed for the 2-year period 1980 to 1981. There were 139 patients with premature rupture of the membranes prior to 37 weeks' gestation, 47 with premature rupture of the membranes less than 24 hours prior to delivery, and 92 in whom premature rupture of the membranes occurred 24 hours or more before delivery. There was a significant difference in the incidence of chorioamnionitis and endometritis between patients in whom premature rupture of the membranes occurred 24 hours or more before delivery and patients in whom delivery took place within 24 hours (p < 0.001). However, neither proiongation of pregnancy with premature rupture of the membranes beyond 24 hours nor use of betamethasone was associated with any increase in maternal or neonatal infectious morbidity. Neonatal mortality was 3.3% and was related only to lower gestational age.     

The relationship between premature rupture of the membranes and the respiratory distress syndrome. An update and plan of management

The records of 340 infants of 36 weeks' gestational age or less were reviewed to study the relationship between premature rupture of the membranes (PRM) and the development of the respiratory distress syndrome (RDS). Twins and infants of diabetic mothers were excluded from the data analysis. PRM of 16 hours or more was associated with statistically significant reduction in the incidence of RDS in infants of 31 weeks' gestational age and older. The association between PRM in excess of 16 hours and survival, however, was only statistically significant for infants of 33 weeks' gestational age and older. The implications of these results and a proposed plan of management for premature infants with PRM are discussed.     

Maternal intravenous ethanol in the prevention of respiratory distress syndrome.

The occurrence of respiratory distress syndrome (RDS) was studied in 68 premature neonates whose mothers were treated with at least one six-hour course of intravenous ethyl alcohol within 48 hours before delivery. At the gestational interval of 28 to 32 weeks, significant differences were observed in the incidence of RDS (p = less than 0.05), in severe RDS (p = less than 0.005), and in the mortality rate from RDS ( = less than 0.05), when compared to premature neonates not treated with alcohol and delivered during the same time interval. Several high-risk factors were found unevenly distributed between treated and control groups of patients, and their relevance to RDS was discussed. Premature rupture of membranes of more than 24 hours did not protect infants from RDS in the patients studied. Explanations for possible mechanisms of action are discussed.     

Chronic fetal stress and the risk of infant respiratory distress syndrome

The relationship between five conditions of chronic fetal stress and the incidence of infant respiratory distress syndrome (RDS) was investigated among 614 premature (less than or equal to 36 weeks) infants delivered at the University of Washington Hospital from 1977 to 1980. The strongest association found was a protective effect of abnormal antepartum testing (nonreactive nonstress test, positive contraction stress test, or low or falling maternal urinary estriols). Among the 45 infants with abnormal antepartum testing, the probability of RDS was 15.0 versus 33.8% for the infants without the complication (odds ratio = 0.35, P less than or equal to .01, adjusted for gestational age and mode of delivery). Rupture of the membranes for greater than 24 hours (N = 151), amnionitis (N = 63), and vaginal bleeding beginning more than 24 hours before delivery (N = 108) were each associated with a reduced risk of RDS (adjusted odds ratios = 0.63, 0.51, and 0.58, respectively, P less than or equal to .05). Hypertensive disease of pregnancy was not associated with a decreased risk of RDS; in fact, the opposite trend occurred (N = 96, odds ratio = 1.67, P = .07). The associations with RDS were not explained by differences between births with and without each complication in terms of gestational age, mode of delivery, absence of labor, administration of antenatal steroids, and other complications of pregnancy. This study adds support to the hypothesis that certain conditions associated with chronic fetal stress lead to an acceleration in pulmonary maturity.     

The relationship between the time from rupture of the membranes to delivery and the incidence of respiratory distress syndrome in premature newborns

The records of 520 deliveries of low birth weight infants were reviewed. A significantly lower incidence of respiratory distress syndrome was seen in cases where the time interval between rupture of membranes and delivery exceeded 1 h as compared to neonates delivered within 1 h after rupture of membranes. Premature infants born after complicated pregnancies had higher rates of RDS than those delivered after uncomplicated pregnancies. It is concluded that postponement of delivery of premature infants for at least a few hours after ROM can reduce the probability of the development of a RDS.     

The use of the amniotic fluid lecithin/sphingomyelin (L/S) ratio, creatinine concentration and nile blue sulphate tests, individually and in combination, in the assessment of fetal lung maturity.

The lecithin-sphingomyelin (LS) ratio is a good, but not absolute, test of fetal lung maturity. A total of 373 infants was delivered within 72 hours of amniotic fluid collection for assessment of the L/S ratio. Five of 43 infants (11-6 per cent) with an L/S ratio of 2-2 or less developed the respiratory distress syndrome (RDS), whereas only one of 320 infants (0-31 per cent) with a higher L/S ratio developed RDS. The risk of RDS could be further defined by using the creatinine concentration (critical value 19 mg/1) and the Nile blue sulphate test (critical value 4 per cent) in combination with the L/S ratio. All three tests were performed in 320 pregnancies and in each instance delivery took place within 72 hours. When all three test results were low, 3 of 5 infants (60 per cent) developed RDS, whereas when all three results were high, none of 175 infants developed RDS. When one or two results were low, 2 of 140 infants (1-4 per cent) developed RDS.     

早产相关因素及早产儿结局临床分析

目的探讨早产发生的高危因素及早产对围生儿的影响。方法选取2001年1月1日-2007年6月30日在我院分娩的早产儿508例作为病例组，并随机选取同期足月分娩产妇508例作为对照组，比较两组产妇的相关情况，围产儿结局，分析早产的高危因素。结果早产儿窒息、RDS发生率及死亡率与足月儿相比差异显著；孕周越小，发病率及死亡率越高。胎膜早破、胎位异常、胎盘因素是造成早产的高危因素。应用地塞米松与未应用者相比，足量应用地塞米松与未足量应用者相比，新生儿并发症发生率、早产儿死亡率均明显降低。孕35周后早产患者，延长孕周并不能降低早产儿并发症发生率及死亡率。结论早产的发生是多种因素的结果。孕周越小，早产儿发病率及死亡率越高。应用糖皮质激素是改善早产儿结局的重要治疗措施。35～36^＋6周PPROM者建议在破膜48h内分娩，以减少早产儿并发症。     

Relationship between duration of preterm premature rupture of membranes and pulmonary maturation.

OBJECTIVE: The purpose of this study was to evaluate the relationship between duration of preterm premature rupture of membranes (PPROM) before delivery and development of respiratory distress syndrome (RDS). METHOD: One hundred and fifty-nine cases of PPROM with gestational ages between 24 and 37 weeks and birth weights between 1300 and 2100 g were studied retrospectively, out of which, 61 infants developed RDS. Subjects with factors known to affect RDS such as: maternal diabetes; hemorrhage; hypertension; fetal asphyxia; multifetal pregnancies; abnormal presentations; or cesarean deliveries were excluded from this study. RESULTS: Out of 94 neonates, who had rupture of membranes (ROM) in less than 12 h, 41 cases (43.6%) developed RDS. Durations of ROM in 19 neonates were between 12 and 24 h and 6 of them (31.6%) developed RDS. In 21 cases whose ROM were between 24 and 48 h, RDS was seen in 4 (19%). However, in 25 subjects whose ROM was greater than 48 h, RDS presented in 10 cases. Statistical analysis, using Bartholomew's test, showed that there exists a reverse linear relationship between duration of ROM and RDS in the first 48 h. However, after 48 h, the risk of RDS increases, which may represent the effect of complications such as: chorioamnionitis; sepsis; and pulmonary hypoplasia on RDS. CONCLUSION: Increasing the duration of PPROM, in the first 48 h, decreases the risk of RDS with a linear pattern.     

The relationship between intrauterine growth restriction and preterm delivery: an empirical approach using data from a European case-control study

Objective To test whether being small for gestational age, defined as having a birthweight less than the 10th centile of intrauterine growth references, is a risk factor for preterm delivery for singleton live births.
Design A case-control study.
Setting Maternity hospitals in 16 European countries.
Sample Four thousand and seven hundred preterm infants between 22 and 36 completed weeks of gestation and 6460 control infants between 37 and 40 weeks of gestation.
Methods Newborn babies are identified as being small for gestational age using customised reference standards derived from models of fetal growth. The impact of being small for gestational age on preterm delivery is estimated using logistic regression.
Main outcome measure Spontaneous or induced preterm delivery.
Results Being small for gestational age is significantly associated with preterm birth, although the magnitude of this association differs greatly by type of delivery and gestational age. Over 40% of induced preterm births for reasons other than the premature rupture of membranes are small for gestational age compared with 10.7% of control infants (OR 6.41). For spontaneous or premature rupture of membranes related preterm births, the association is also significant, but weaker (OR 1.51). The relationship between growth restriction and preterm delivery is strongest for preterm births before 34 weeks of gestation.
Conclusions These findings highlight the phenomenon of abnormal fetal growth in all premature infants and, in particular, infants delivered by medical decision for reasons other than premature rupture of membranes. The observed association between being small for gestational age and preterm delivery among spontaneous preterm births merits further attention because the causal mechanisms are not well understood.     

Chorioamnionitis in relation to gestational outcome in a Swedish population

In a histopathological study, from a homogeneous Swedish population with a better than average socio-economic standard, placentas from 161 singleton infants small for gestational age (SGA) and 322 singleton infants appropriate for gestational age (AGA) were examined for the presence of inflammation in the placental parenchymal membranes, cord and decidua. Acute chorioamnionitis including funiculitis was found in 13.4% of the total material, in 17% of term AGA-infants (GA, greater than or equal to 38 weeks), in 13% of preterm AGA-infants (less than or equal to 37 weeks) and in 6.8% of SGA-infants (p less than 0.001, compared to term AGA). Acute chorioamnionitis was correlated to vaginal delivery (p less than 0.01), rupture of the membranes greater than 24 hours (p less than 0.01), nulliparity (p less than 0.05) and amniocentesis (RR = 1.7). In nulliparous, chorioamnionitis was related to duration of labor greater than 16 hours (p less than 0.01). Streptococcal (p less than 0.01) and anaerobic vaginal infections (p less than 0.05) were also related to chorioamnionitis. Of 17 infants with sepsis, 6 had chorioamnionitis (p less than 0.05). Decidual inflammation was chronic in type and found in 4.5% of the placentas and was not related to chorioamnionitis, but to parity (p less than 0.05) and term AGA-infants (p less than 0.001).     

Maternal and perinatal outcome of expectant management of premature rupture of membranes in the midtrimester

The purpose of this clinical investigation was to determine the maternal and perinatal results of continuing pregnancy in 118 consecutive patients with premature rupture of the membranes at 16 to 26 weeks. The mean gestational age at diagnosis of premature rupture of the membranes was 23.1 +/- 2.7 weeks, with a median of 23.5. The interval from rupture to delivery ranged from 1 to 152 days, with a mean of 13. There was no correlation between gestational age at the time of rupture and the latency period. Thirty-five patients received tocolytic agents and 24 received steroids. Forty-eight percent were delivered within 3 days, 67% within 1 week, and 83% within 2 weeks. There was one maternal death from sepsis; 46 (39%) had amnionitis, and 8 (6.8%) had abruptio placentae. The mean gestational age at the time of delivery was 24.7 +/- 3.6 weeks. The 118 pregnancies resulted in 124 births. There were 17 stillbirths and 67 neonatal deaths, for a total perinatal mortality of 67.7%. In patients with premature rupture of the membranes at less than or equal to 23 weeks the perinatal survival rate was 13.3%, while it was 50% in patients with premature rupture of the membranes at 24 to 26 weeks (p less than 0.0001). Information was charted at 3 to 36 months for 34 of 40 surviving infants. The intact survival rate in this group was 67%, and 33% had some form of developmental abnormality. Expectant management in such cases can be justified in only a limited number of patients (patients who understand and accept the risks and patients beyond 23 weeks of gestation).     

Contemporary diagnosis and management of preterm premature rupture of membranes

Spontaneous rupture of membranes (ROM) is a normal component of labor and delivery. Premature ROM (PROM) refers to rupture of the fetal membranes prior to the onset of labor irrespective of gestational age. Once the membranes rupture, delivery is recommended when the risk of ascending infection outweighs the risk of prematurity. When PROM occurs at term, labor typically ensues spontaneously or is induced within 12 to 24 hours. The management of pregnancies complicated by preterm PROM (defined as PROM occurring prior to 37 weeks of gestation) is more challenging. Preterm PROM complicates 2% to 20% of all deliveries and is associated with 18% to 20% of perinatal deaths. Management options include admission to hospital, amniocentesis to exclude intra-amniotic infection, and administration of antenatal corticosteroids and broad-spectrum antibiotics, if indicated. This article reviews in detail the contemporary diagnosis and management of preterm PROM.     

The Effects of Antenatal Steroid Use in Premature Rupture of Membranes

Summary: We sought to determine if antepartum steroid treatment offers any clinical benefits to patients with premature rupture of membranes. One hundred and forty-five maternal-neonatal pairs were studied. Forty-five maternal-neonatal pairs with premature, preterm rupture of membranes received steroids during 24–35 weeks' gestation. One hundred maternal-neonatal pairs received no antenatal steroids. The 2 groups were identical with regard to gestational age at rupture of membranes, gravity, parity, race, fetal gender, socioeconomic status, smoking, and preterm labour risk factors. Study of the data revealed that maternal chorioamnionitis was less frequent in the steroid group (p<0.001). Bronchopulmonary dysplasia (oxygen dependent at discharge at term gestational age) was less frequent in the steroid group (p<0.05). The remainder of the data revealed no statistically significant differences in preterm delivery rate, necrotizing enterocolitis, respiratory distress syndrome, intraventricular haemorrhage rate or severity of haemorrhage, hospital days, latency to delivery, or ventilator days. Antepartum steroid use in preterm rupture of membranes appears to offer clinical benefit in premature infants by lessening the rate of bronchopulmonary dysplasia in those infants receiving antepartum steroids.     

Lethal lung hypoplasia in infants after prolonged rupture of membranes

A retrospective study to detect the frequency of lethal lung hypoplasia in 48 cases with prolonged rupture of membranes (greater than 7 days) before 34 weeks' gestation was made. Fourteen infants died (29%), but only four deaths (8.3%) were due to lung hypoplasia. Three infants with lung hypoplasia had their membranes ruptured before 20 weeks' gestation and showed echoscopically a persistent oligohydramnios, as did the one with rupture at 26 weeks. Neither the duration of rupture of membranes nor the gestational age at the time of rupture showed any influence on the occurrence of lung hypoplasia. The rupture of membranes before 20 weeks' gestational age with resulting persistent oligohydramnios will certainly lead to lung hypoplasia.     

Perinatal factors associated with the respiratory distress syndrome

Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses.     

Acceleration of pulmonary surfactant maturation in stressed pregnancies: A study of neonatal lung effluent

To determine the maturation of pulmonary surfactant at birth, phospholipid patterns in tracheal or pharyngeal aspirates of 54 newborn infants were analyzed by two-dimensional thin-layer chromatography. The compositions of phospholipids and their surface tension-lowering abilities were assessed after gestations with various complications. Preterm infants with respiratory distress syndrome (RDS) lacked phosphatidylglycerol and had lower lecithin/sphingomyelin ratios than infants without RDS. An acceleration of both phosphatidylcholine (lecithin) and phosphatidylglycerol concentrations was observed in 21 preterm infants born after prolonged rupture of the membranes and treatment with isoxuprine. In these infants, the phospholipid pattern of lung effluent was similar to that of term infants even at gestational ages ≤30 weeks. Biochemical lung maturation was delayed in anencephalic infants, infants of diabetic mothers, and one infant of a mother with hypothyroidism.     

The relationship between delivery mode and mortality in very low birthweight singleton vertex-presenting infants

OBJECTIVE: To investigate the factors associated with caesarean delivery and the relationship between mode of delivery and mortality in singleton vertex-presenting very low birthweight (< or = 1500 g) live born infants. DESIGN: Observational population-based study. SETTING: Data collected from all 28 neonatal departments comprise the Israel National Very Low Birth Weight Infant Database. POPULATION: 2955 singleton vertex-presenting very low birthweight infants registered in the database from 1995 to 2000, and born at 24-34 weeks of gestation. METHODS: The demographic, obstetric and perinatal factors associated with caesarean delivery and subsequent mortality were studied. The independent effect of the mode of delivery on mortality was tested by multiple logistic regression. MAIN OUTCOME MEASURE: Mortality was defined as death prior to discharge. RESULTS: Caesarean delivery rate was 51.7%. Caesarean delivery was directly associated with increasing maternal age and gestational age, small for gestational age infants, maternal hypertensive disorders and antepartum haemorrhage, and was inversely related to premature labour and prolonged rupture of membranes. Factors associated with increased survival were increasing gestational age, antenatal corticosteroid therapy, maternal hypertensive disorders and no amnionitis. Mortality rate prior to discharge was lower after caesarean delivery (13.2% vs 21.8%), but in the multivariate analysis, adjusting for the other risk factors associated with mortality, delivery mode had no effect on infant survival (OR 1.00, 95% CI 0.74-1.33). In a subgroup with amnionitis, a protective effect of caesarean delivery was found. CONCLUSIONS: Caesarean delivery did not enhance survival of vertex-presenting singleton very low birthweight babies. Caesarean delivery cannot be routinely recommended, unless there are other obstetric indications.     

Outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks of gestation

OBJECTIVE: To identify factors influencing the outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks' gestation. DESIGN AND POPULATION: All premature infants with gestational age <34 weeks, either inborn or outborn, with history of rupture of membranes before 25 weeks' gestation, admitted to our NICU between January 1992 and July 1997, were eligible for this retrospective study. Collected information included birth weight, gestational age at rupture of membranes and at delivery, duration between rupture of membranes and delivery (latency period), severity of oligohydramnios, pre- and post-natal managements, and follow-up of survivors. RESULTS: A total of 28 neonates fulfilled the inclusion criteria. Despite new strategies of ventilation and optimal management, the overall mortality rate was 43% (12/28). Nonsurvivors were significantly less mature at rupture of membranes, and had severe oligohydramnios (anamnios). We also noted less antenatal corticosteroids and antibiotic therapy in this group. Nine of eleven infants (82%) following rupture of membranes before 22 weeks' gestation died shortly after birth. The two remaining infants developed severe bronchopulmonary dysplasia. Nine deaths occurred in thirteen cases (69%) of anamnios. The major death causes were refractory respiratory failure and neurologic complications. Half of all survivors (8/16) developed bronchopulmonary dysplasia. CONCLUSION: The outcome of premature infants following prolonged premature rupture of membranes before 25 weeks' gestation is influenced by gestational age at rupture, severity of oligohydramnios, and antenatal antibiotics and corticosteroids. Neonates with rupture of membranes before 22 weeks have a very low chance of survival at the present time.     

早期 晚期早产儿与足月新生儿 呼吸窘迫综合征临床比较分析

目的　 探讨早期、晚期早产儿与足月儿呼吸窘迫综合征（RDS）的发病趋势和临床特征的差异,为临床合理诊治提供依据。方法　2006年1月至2010年12月在郑州大学第三附属医院住院的963例RDS患儿根据胎龄不同分为早期早产儿组（ < 34周）679例,晚期早产儿组（34～ < 37周）204例,足月儿组（≥37周）80例,分别对各组患儿的发病率、入院情况、高危因素、临床诊治、预后及并发症进行比较。结果　RDS的发病率逐年增加,均以早期早产儿占多数,晚期早产儿和足月儿RDS比例有增多趋势;RDS患儿男婴超过女婴（P < 0.05）,且胎龄和体重越大,男婴比例越高;足月儿RDS组产前糖皮质激素使用率明显低于早产儿组;早产儿发生RDS的高危因素主要有胎膜早破、胎盘异常、母亲妊娠高血压疾病,足月儿发生RDS的高危因素主要是择期剖宫产与感染;晚期早产儿与足月儿RDS的临床诊断和应用肺泡表面活性物质（PS）时间均晚于早期早产儿;足月儿RDS应用机械通气比例明显高于早产儿,其临床治愈率高（P < 0.05）,在死亡率方面与早产儿组无差别;但并发气胸的比例高于早产儿组（P < 0.05）。结论　新生儿呼吸窘迫综合征（NRDS）发病率逐年增高,晚期早产儿和足月儿RDS比例有增多趋势;早期、晚期早产儿与足月儿RDS在性别比例、高危因素、起病特点、治疗反应与并发症方面均存在差异,RDS的诊治需要考虑胎龄因素。足月儿RDS多与择期剖宫产、感染有关,发病相对较晚,容易合并气胸,应引起足够重视。