Antenatal Steroid Administration Research Articles

Relationship Between Antenatal Steroid Administration and Blood Pressure Regulation in Preterm Infants 1054

Increases in neonatal blood pressure (BP) have been reported to occur with antenatal steroid (ANS) administration for fetal lung maturation in some, but not all reports. Prior to 5/1/94, ANS were used rarely at Parkland Memorial Hospital. However, after that date ANS were commonly used for pregnancies between 24-34wk gestation. To study the relationship between ANS use and neonatal BP regulation in the first 72h after birth, we examined infants with birth weight (BW) ≤1500g. 70 neonates born between 5/1/94 and 4/30/95 were exposed to ANS (Group I) and were compared with 46 matched non-exposed infants born between 5/1/93 and 4/30/94 (Group II). Infants were matched for BW(1166±253g vs 1100±241g; mean±SD), gestational age(28.7±2.1wks vs 28.9±1.8wks), gender and race. The groups were comparable for route of delivery, method of measuring BP (direct vs oscillometric), frequency of RDS, surfactant Rx, need for assisted ventilation, airleak, and fluid intake. There were no significant differences between Groups for systolic (SBP), diastolic (DBP) or mean (MBP) BP at 1, 6, 12, 24, 48 and 72h after birth (Table:mmHg). Further, the need for volume and/or pressor support did not differ significantly, 11.4% vs 6.5%, respectively. When only Group I infants whose mothers received ≥3 doses of ANS (N=35) were examined, there still were no differences between groups. BP differences were not observed when infants with BW ≤750g or≤1000g were analyzed. We conclude from these results that ANS did not modify the initial BP, subsequent BP measurements during the first 72h after birth, the rate of rise of neonatal BP in the first 72h postnatally, or the use of volume expanders or pressor agents in infants ≤1500g BW.

Repeated Courses of Steroids in Preterm Membrane Rupture Do Not Increase the Risk of Histologic Chorioamnionitis

Antenatal administration of steroids (betamethasone 12 mg i.m. twice q 24 hr) enhances fetal lung maturation and reduces neonatal morbidity in preterm prelabor rupture of membranes (PROM). However, the risks of repeated administration of steroids 7 days after the initial course are unknown. We evaluated the prevalence of histologic evidence of chorioamnionitis in patients receiving single versus multiple courses of steroids for fetal lung maturation. We performed a retrospective analysis of consecutive cases of preterm PROM at or = 2 courses of steroids (n = 89). Placental pathology examination was performed after delivery, and histologic evidence of acute placental inflammation was determined and scored semiquantitatively on a scale of 0-4, as previously described. Potential confounding variables considered were: presence of oligohydramnios (vertical pocket of amniotic fluid < or = 1 cm at ultrasound), onset of labor prior to delivery, gestational age at delivery, and mode of delivery. The three groups were comparable for gestational age at membrane rupture and at delivery, rate of oligohydramnios, labor prior to delivery, and mode of delivery. Administration of multiple courses of steroids was associated with a decrease in the rate of clinical chorioamnionitis (p < 0.0001) and severity of histologic acute placental inflammation (mean +/- SD total score of acute inflammation: 10.7 +/- 7.2 vs. 7.3 +/- 6.0 vs. 6.9 +/- 6.0, p = 0.005) compared with the groups receiving no steroids or administration of a single course of steroids. In preterm PROM at < 32 weeks, repeated administration of courses of steroids is not associated with an increase in the prevalence of clinical or histologic evidence of infectious outcome. These findings may reflect a greater likelihood for noninfected patients to remain quiescent and thus receive repeated courses of steroids.

Are Perinatal Factors Predictive of Optimal School Age Outcome in the ELBW Infant? † 1241

The incidence of major developmental disabilities in the extremely low birth weight (ELBW) infant has remained stable despite dramatic improvement in survival. A subset of these children consistently overcome the odds, are neurologically intact, and demonstrate normal cognitive and academic skills. The purpose of this study is to identify perinatal predictors of optimal school age outcome in a sample of ELBW children. The study group consists of 257 surviving ELBW infants (<1001 grams) admitted to Vanderbilt University Hospital July 1982-July 1989. Information regarding presence of vision or hearing impairment, cerebral palsy, mental retardation, and school difficulty(need for special education or remedial resources after meeting school system eligibility criteria) at 7-9 yrs is available for 214 of 257 children (83%). The survivors were divided into three mutually exclusive subgroups: Group 1(n=66) is children with optimal outcome, no disability or school difficulty; Group 2 (n=71) is children with school difficulty, but no major difficulty; Group 3 (n=77) is children with any major disability. Data regardingobstetric risk (prenatal care, maternal smoking, presentation and mode of delivery, antenatal steroid administration, amnionitis, fetal heart rate tracing), neonatal course (birth weight, gestation, BPD, IVH, length of stay) and sociodemographics (race, gender, maternal age, education, marital status, social risk score) were analyzed by ANOVA and chi squares in relation to school age outcome for each of the three groups. The ELBW children with major developmental disability (Group 3) had significantly lower birth weight, shorter gestation, longer hospitalization, and more severe IVH than the remaining two thirds of the survivors in Groups 1 and 2 (p<0.05). However the children with optimal school age outcome (Group 1) and the children experiencing school difficulty (Group 2) did not differ significantly from each other on any of the obstetric, neonatal, or sociodemographic variables listed above, with the exception of gender. In our sample, the ELBW child spared major disability still has a 50% risk of experiencing school difficulty regardless of perinatal factors. If optimal outcome cannot be predicted by perinatal factors, then further research is important to identify mechanisms to reduce morbidity and promote optimal cognitive outcome in the rapidly growing population of ELBW survivors.

Does Antenatal Indomethacin Decrease the Incidence of Severe Intraventricular Hemorrhage? 1173

Postnatal administration of indomethacin to preterm infants has been associated with a decreased incidence of severe intraventricular hemorrhage(IVH). However, maternal administration of indomethacin for preterm labor has been associated with increased neonatal complications, including severe IVH. Hypothesis: Antenatal indomethacin decreases the incidence of IVH in extremely premature infants. Method: Records of neonates between 24-28 wks of gestation, born from 1995-1997 to mothers in preterm labor were obtained from the hospital data base. Infants with prolonged premature rupture of membranes (> 18 hrs), no head ultrasound performed or incomplete records were excluded. Demographic variables were evaluated using T-test or Chi-square, as appropriate. Results: 109 infant met inclusion criteria, 26 infants were exposed to indomethacin and 83 were not. There were no difference between the two groups with respect to gestational age, birth weight, route of delivery, Apgar scores and maternal complications. Although the incidence of grades III-IV IVH was lower in the infants exposed to indomethacin (7% vs. 18%), this was not statistically different. There were no difference between the indomethacin-exposed and control groups with regard to incidence of NEC (15% vs. 13%), BPD (56% vs. 60%), PDA (50% vs. 66%), air leak(12% vs 24%), pulmonary hemorrhage (19% vs. 15%) and number of doses of surfactant (2.4% vs. 1.8%). Further analysis revealed that more mothers of indomethacin-exposed infants were given steroids prior to delivery (96% vs 61%, p < 0.001). Antenatal steroid administration was associated with a lower incidence of severe IVH (14% vs 45%, p < 0.001). Conclusion: Antenatal exposure to indomethacin among preterm infants is not associated with lower incidence of severe IVH nor increased occurrence of neonatal complications. Antenatal steroid administration significantly lowers the incidence of severe IVH in these infants.

Assessment of Maternal Antenatal Steroid Use for the Treatment of Very Low Birth Weight Infants (VLBWI) 1184

This study examined demographic data to determine the relationship between maternal factors and antenatal corticosteroid administration based on the NIH Consensus Conference guidelines published in 1995. A retrospective study of mothers delivering VLBWIs at Tod Children's Hospital in Youngstown, Ohio between April 1, 1995 and April 31, 1997 was conducted (n=47). Variables examined included treatment status, maternal race, adequacy of prenatal care, maternal age, parity, infant weight and time between maternal hospital admission and delivery. All mothers admitted more than 6 hours before delivery received some corticosteroid treatment, while 73.1% of those presenting at less than 6 hours received no treatment. 65.5% of women receiving adequate prenatal care received treatment while all women lacking adequate prenatal care failed to be treated. Time between release of the NIH guidelines and delivery for women receiving any therapy was 16.04±7.27 months, while those receiving no therapy delivered 8.24±4.85 months after release of the guidelines. Factors not found to be significant included maternal race, age and parity. We conclude that practicing obstetricians have gradually adopted NIH guidelines concerning antenatal steroid administration. We speculate that educational efforts designed to improve the awareness of preterm labor may result in earlier presentation of mothers in preterm labor, resulting in an increase in the number of VLBWI receiving the benefits of antenatal corticosteroid therapy.

An audit of the antenatal administration of steroids in women at risk of preterm delivery

An audit of the antenatal administration of steroids in women at risk of preterm delivery

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage

Objective: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, ≤1500 g). Method: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. Setting: Seven tertiary care neonatal-perinatal centers. Results: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. Conclusion: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH. (Arch Pediatr Adolesc Med. 1996;150:491-497)

Perinatal outcome following conservative management of mid-trimester pre-labour rupture of the membranes.

To assess perinatal outcome and the effect of antenatal steroid use following conservative management of 86 consecutive singleton pregnancies complicated by pre-labour rupture of membranes (ROM) in the mid-trimester (13-26 weeks; mean 22.8 weeks). Review of obstetric and neonatal case notes between 1 January 1990 and 31 December 1993. The duration of ruptured membranes (latent period) ranged from 1.25 to 105 days (mean 23.8 days; median 14 days) and was inversely related to gestational age at ROM. There was clinical evidence of chorioamnionitis in 39.5% with placental histological changes consistent with chorioamnionitis in 76.6%. All infants were delivered before 33 weeks gestation (mean 26 weeks). Overall, the mortality rate was 43.0% but 62.5% in infants with ROM before 24 completed weeks gestation. Adverse outcome (defined as death, severe intraventricular haemorrhage (IVH) or periventricular leucomalacia (PVL)) occurred in 46.5% and was significantly related to both gestation at delivery and gestation at ROM. In the group (n = 40) with ROM before 24 weeks gestation, adverse outcome occurred in 65% and was inversely related to gestation at ROM independent of gestation at delivery. Antenatal steroid administration resulted in less adverse outcome independent of gestation at delivery (OR 0.31; 95% CI (0.09-0.98; P = 0.046)). From the neonatal perspective conservative management is justified for pregnancies with ROM at or after 24 weeks gestation; in this group the use of antenatal steroids prior to delivery may improve perinatal outcome. A poor outcome is associated with ROM that occurs before 24 weeks gestation.

Prenatal and Perinatal Risk and Protective Factors for Neonatal Intracranial Hemorrhage

Objective: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, ≤1500 g). Method: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. Setting: Seven tertiary care neonatal-perinatal centers. Results: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. Conclusion: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH. (Arch Pediatr Adolesc Med. 1996;150:491-497)

New South Wales newborn and paediatric emergency transport service (NETS)

Objective: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very-low-birth-weight infants accounting for sociodemographic, obstetric and perinatal variables. Study design: Ninety-one premature infants with birth weights of 750–1250 g delivered between 1990 and 1994 in a hospital providing neonatal intensive care were compared with 76 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistically significant association with the outcome variables and dissimilar distributions in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. Results: No statistically significant differences between the outcome variables of the two populations examined were observed, whether before or after accounting for the covariates. The odds ratios (outborns relative to inborns) were 1.18 for mortality, 1.25 for bronchopulmonary dysplasia and 1.53 for severe intraventricular hemorrhage. In the multivariate analyses, respiratory distress syndrome was significantly associated with mortality; both low birth weight and the presence of respiratory distress syndrome were associated with the development of bronchopulmonary dysplasia; the evolvement of severe intraventricular hemorrhage was associated with respiratory distress syndrome, initial low Apgar score, advanced multiparity and delivery at the 28–29th week compared to the 23rd–27th week. Antenatal steroid administration had a protective effect. Conclusion: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Improvement in medical and nursing care prenatally and at delivery and transportation, including frequent administration of antenatal steroids and earlier administration of surfactant prior to transportation, may minimize the disadvantage of delivery in a referring hospital.

Antenatal steroids: miracle drug for preemies.

Antenatal corticosteroid administration has been unequivocally demonstrated to reduce neonatal morbidity and mortality. In addition to its well-documented role in reducing respiratory distress syndrome, evidence is accumulating indicating the global maturational effect of this therapy in the growing fetus. New data demonstrates, the hitherto relatively not well known, beneficial effects of this mode of therapy on renal, cardiovascular, gastrointestinal, endocrinal and cerebral maturation. Despite its well proven efficacy and safety, this therapy is used only in a small fraction of eligible mothers. In this article, biological basis of antenatal steroids use, clinical benefits including those to extremely premature infants, indications for their administration, treatment regimens, practice variations in their administration, cost analysis, and some directions for future research are reviewed. It is hoped that given the evidence reviewed in this article, the use of antenatal steroids administration in proper clinical settings will increase with a significant impact in reducing the neonatal morbidity and mortality.

A retrospective analysis of the effect of antenatal steroid administration on the incidence of respiratory distress syndrome in preterm twin pregnancies.

Respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm twin deliveries. Therapy with corticosteroids has been shown to reduce the incidence of RDS in preterm singleton gestations but similar reductions in twin pregnancies have not been demonstrated. Maternal and neonatal medical records were reviewed from twins delivered between 24 to 34 weeks gestation over the period of January 1, 1990 to December 31, 1994. Twenty-one pairs of twins received optimal steroid treatment defined as the use of two 12 mg doses of betamethasone, with birth occurring between 24 hours and 7 days after the first dose. Sixty-three pairs received no treatment. The mean gestational age at delivery was 29.9 +/- 2.6 weeks. No decrease was seen in the incidence of RDS (optimal steroid 70.7% versus no treatment 68.0%, unadjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 0.49 to 2.65). Multivariate logistic regression showed no statistical difference in the incidence of RDS in the optimal steroid compared to the no treatment group (adjusted OR 0.63, 95% CI 0.2 to 1.95). No statistical differences were noted in the incidence of mechanical ventilation (58.6% versus 55.4%, p = 0.83), median duration of intubation (5.0 versus 5.0 days, p = 0.47), the median maximum inspiratory pressure requirements (20.0 versus 22.0 mm Hg; p = 0.15) in the optimal treatment versus no treatment group, respectively. The current regimen of antenatal corticosteroids utilized in twin pregnancies does not reduce the incidence of RDS.

Antenatal steroid administration is associated with an improved chance of intact survival in preterm infants.

Antenatal steroid administration reduces mortality in preterm infants. We used logistic regression analysis to explore the influence of various factors on intact survival in a population of 798 very low birth weight infants admitted between 1985 and 1992. Antenatal steroid administration (n = 87) was associated with an improved chance of normal survival with an odds ratio of 3.0 (95% confidence intervals from 1.5 to 5.9). Other factors associated with improved outcome were a normal cranial ultrasound image or one showing subependymal haemorrhage, female sex, a 5 min Apgar score above 5, low inspired oxygen concentration and higher birth weight. Year of birth was not associated with a consistent trend to improve outcome over this period and surfactant administration rates were constant throughout. These results endorse the current recommendations to increase the use of antenatal steroid therapy. Antenatal steroid administration was associated with a threefold improvement in the chance of normal survival for very low birth weight infants as assessed at 18 months. These results suggest that the reduction in periventricular haemorrhage after antenatal steroid use is translated into a better longterm outcome.

Antenatal steroid administration is associated with an improved chance of intact survival in preterm infants

Antenatal steroid administration is associated with an improved chance of intact survival in preterm infants

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network.

To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, < or = 1500 g). Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. Seven tertiary care neonatal-perinatal centers. By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH.

Relationship between antenatal steroid administration and grades III and IV intracranial hemorrhage in low birth weight infants

Relationship between antenatal steroid administration and grades III and IV intracranial hemorrhage in low birth weight infants

Maternal toxemia is associated with reduced incidence of germinal matrix hemorrhage in premature babies.

To evaluate prenatal and perinatal risk factors for development of germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), we conducted a prospective epidemiologic study of 449 babies whose birth weight was less than 1501 grams. This study permitted us to test our previously generated hypothesis that babies born to mothers with preeclampsia were at substantially reduced risk of developing GMH-IVH. Seventy-two (16%) of the babies in this population developed GMH-IVH. One (2.5%) of the 40 mothers with a diagnosis of preeclampsia and 71 (17.4%) of 409 mothers without preeclampsia gave birth to babies who developed GMH-IVH. GMH-IVH was seen in 6/107 (5.6%) of babies born to women with hypertension including 4/69 (5.8%) of babies born to women with pregnancy-induced hypertension, compared to 66/352 (18.8%) of babies born to mothers who did not have hypertension. Only 7.3% (8/108) of babies born to women who had proteinuria had GMH-IVH, compared to 18.3% (64/350) of babies whose mothers did not have proteinuria. GMH-IVH was seen in 5/89 (5.6%) of babies whose mothers had both hypertension and proteinuria, whereas 63/332 (19%) of babies born to mothers who lacked both factors, developed GMH-IVH. In stepwise logistic regression analysis, these significant findings were not explained by the presence of labor, postnatal acidemia, need for intubation, antenatal administration of steroids, birth weight, or gestational age. In addition, we found that maternal receipt of magnesium sulfate was associated with diminished risk of GMH-IVH even in those babies born to mothers who apparently did not have preeclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased incidence of respiratory distress syndrome in infants following pregnancies complicated by hypertension.

We assessed the relationship between maternal hypertension during pregnancy and the incidence of respiratory distress syndrome (RDS) in 263 infants born at 32 weeks' gestation or less. Two-hundred and twenty-three mothers were normotensive and 40 were hypertensive. RDS occurred significantly more commonly in infants of hypertensive mothers than in controls (60% vs 33%; p = 0.001). The association between maternal hypertension and an increased rate of RDS remained after adjustment for differences between groups with respect to gestational age, mode of delivery, administration of antenatal steroids and other complications of pregnancy, except for delivery in the absence of labour. The increased rate of RDS related to the severity of hypertension but did not relate to the duration of hypertension or to maternal treatment with beta-blockers. In those infants who developed RDS there was no significant difference in the severity of the illness between the hypertensive group and the controls.

Perinatal factors and the development of chronic lung disease in preterm infants: a case control study.

A case control study of neonates was performed to determine those factors contributing to the development of chronic lung disease (CLD). During the 5 years 1981-84 there were 487 neonatal survivors at gestations of 25-32 weeks; 391 of these developed respiratory failure (oxygen therapy required for more than 6 h). Fifty-six of the latter developed CLD (oxygen therapy required for more than 28 days and a coarse reticular pattern on chest X-ray). These neonates were predominantly of the shortest gestational ages, regardless of the initial chest X-ray diagnosis. Forty-three of these infants with CLD were matched for gestation and initial chest X-ray appearance (respiratory distress syndrome, n = 20; normal, n = 15; non-specific, n = 8) with 42 control infants. The mean duration of oxygen therapy (P less than 0.001), maximum FiO2 (P less than 0.001), incidence (P less than 0.01) and duration of intermittent positive pressure respiration (IPPR; P less than 0.05) and peak IPPR (P less than 0.05) were significantly greater in the CLD group. Mean birthweight (P less than 0.001), arterial cord pH (P less than 0.05) and base excess (P less than 0.05) were significantly lower in the CLD group. Factors that were not statistically significant in the development of CLD included antenatal fetal heart rate abnormality, hypertensive disease of pregnancy, acute intrauterine infection (chorioamnionitis or umbilical vasculitis), administration of antenatal steroids, sex, patent ductus arteriosus and pneumothorax. The association between CLD and ventilator/oxygen therapy is confirmed. Contrary to other reports, male sex, clinical patent ductus arteriosus and pneumothorax were not associated with CLD.

1094 THE EFFECT OF BETAMETHASONE ON THE CHEMOTACTIC RESPONSE OF NEONATAL NEUTROPHILS

Antenatal maternal steroid administration has been widely used to accelerate fetal lung maturation. There is evidence that this therapy may be associated with an increased risk of infection in the neonate. Inhibition of multiple aspects of neutrophil (PMN) function by glucocorticoids has been widely documented in adults and children. Because the host defense system of the neonate is less than fully competent, further compromise of existing PMN function may be of major importance. We performed an in vitro study to determine the effect of betamethasone on the random migration (chemokinesis) and directed migration (chemotaxis) on neonatal PMN. A separated cell micropore filter assay was used to study the effect of betamethasone on PMN's obtained from cord blood of healthy term neonates. The addition of therapeutic concentrations of betamethasone (1.0 μgm/100 ml) resulted in a significant inhibition in PMN chemokinesis and chemotaxis. Betamethasone inhibition of PMN motility, if present in vivo may lead to a clinically significant susceptability to perinatal bacterial infection.