In vitro quantification of dexamethasone-induced surfactant protein B expression in human lung cells.

OBJECTIVE: To determine whether the effect of a single 48-h exposure to dexamethasone in human lung cells is limited to 7-8 days. STUDY DESIGN: We used the NCI-H441 cell line, in which stability can be maintained beyond 7 days. The outcome was the stimulatory effect of dexamethasone on surfactant protein B (SP-B) gene transcription as expressed by SP-B mRNA accumulation. The experiment was conducted five times, in parallel with control. SP-B mRNA was determined at baseline, 48 h after dexamethasone exposure, and at 48-h intervals thereafter, up to 14 days, by quantitative reverse transcription polymerase chain reaction. Comparisons were made by the Mann-Whitney test. RESULTS: In conditions of our experiment, the inductive profile of SP-B mRNA after exposure to dexamethasone demonstrated maximal stimulation at 48 h (13-fold over control). Subsequently, there was a decline in mRNA, with return to near control levels by day 8, suggesting reversibility of dexamethasone action. CONCLUSION: Our data support the view that the surfactant-inducing properties of corticosteroids are limited to 7-8 days.

Urinary tract infections during pregnancy.

Urinary tract infections are relatively common in pregnancy and may result in significant morbidity for the pregnant woman and fetus. The authors recommend that all pregnant women be screened for the presence of bacteriuria at their first prenatal visit. Failure to treat bacteriuria during pregnancy may result in as many as 25% of women experiencing acute pyelonephritis. Women with acute pyelonephritis may sustain significant complications, such as preterm labor, transient renal failure, ARDS, sepsis and shock, and hematologic abnormalities. Pregnant women with urinary tract infections should be followed up closely after treatment because as many as one third will experience a recurrence.

Effects of pregnancy on specific diseases.

Of the numerous physiological changes associated with pregnancy that may have effects on various diseases, the marked increase in blood volume probably exerts the most pronounced effect. This increase may affect the serum level of many medications, as well as affecting various laboratory tests. Other important changes occur in the renal and hepatic system, which in turn may affect the clearance and metabolism of certain drugs and medications. Moreover, the response to and treatment of various diseases during pregnancy may be affected by the "attitude" of the health care providers who are often reluctant to perform certain diagnostic tests and procedures on the pregnant woman.

Antenatal corticosteroids in women with preterm premature rupture of the membranes.

The authors believe that the literature provides sufficient evidence that antenatal corticosteroid administration is beneficial and safe even in conditions of ruptured membranes. The evidence by now is remarkably robust and one can be reasonably confident regarding the benefits of antenatal corticosteroids in the setting of ruptured membranes. As recently stated by a group of investigators from New Zealand, including Liggins, the originator of this historical medical intervention (antepartum corticosteroids), the safety and efficacy of corticosteroids in conditions of ruptured membranes is beyond any doubt. It is time to accept this reality and to move on to other unresolved issues, like the optimal dose and corticosteroid preparation, the optimal timing of treatment, or the optimal exposure interval.

Other factors/conditions associated with cerebral palsy.

The cause for most cases of cerebral palsy is unknown. There are however, risk factors that have been associated with this chronic neuromuscular disease. The objective of this article is to review the maternal and fetal conditions (other than asphyxia and infection) strongly associated with increased rate of cerebral palsy. What remains to be elucidated is whether or not these associations are causative.

Infection and cerebral palsy.

Recent data suggest a possible association of infection and cerebral palsy. The objective of this article is to examine the relationship between intrauterine infection, fetal infection, and long-term neurological dysfunction. In some children maternal infection is associated with brain white matter damage, periventricular leukomalacia, and cerebral palsy.

Association between umbilical blood gas parameters and neonatal morbidity and death in neonates with pathologic fetal acidemia.

OBJECTIVE: Our purpose was to correlate umbilical artery blood gas parameters with neonatal death and indicators of morbidity in neonates with pathologic fetal acidemia (pH <7.0). STUDY DESIGN: We reviewed maternal and neonatal charts of 93 neonates with an umbilical artery pH <7.0 who were delivered at 2 university-based centers. The relationships between umbilical artery pH, PO (2), PCO (2), bicarbonate, base deficit, and neonatal variables-death, need for intubation, cardiopulmonary resuscitation, seizures, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage, meconium, sepsis, and intrauterine growth restriction-were determined with the Student t test, Mann-Whitney U test, and multiple logistic regression analysis. Data are presented as either median with 25th-75th percentiles or mean +/- SD. RESULTS: The mean gestational age at delivery was 37.9 +/- 3. 6 weeks, and the mean birth weight was 3003 +/- 866 g. There was no relationship between neonatal death, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, patent ductus arteriosus, meconium, sepsis, and any umbilical artery blood gas parameter. The PO (2) was not related to any of the variables studied. A lower umbilical artery pH was associated with hypoxic-ischemic encephalopathy (6.69 vs 6.93, P =.03), cardiopulmonary resuscitation (6.83 vs 6.93, P =.03), seizure (6.75 vs 6.93, P =.02), intubation (6.83 vs 6.94, P <.001), and intrauterine growth restriction (6.72 vs 6.93, P =.01). Greater mean base deficit was associated with seizure (20.6 vs 15, P =.01), intubation (18.0 vs 13.7, P <.001), cardiopulmonary resuscitation (18.5 vs 15.0, P =.03), intrauterine growth restriction (22.0 vs 14. 0, P =.02), and hypoxic-ischemic encephalopathy (24.0 vs 14.5, P =. 03). Arterial PCO (2) was higher only in infants with hypoxic-ischemic encephalopathy (138 vs 95.5, P =.048), intubation (106.0 vs 90.5, P =.003), and cardiopulmonary resuscitation (106.5 vs 93.0, P =.04). After control for birth weight and gestational age in the multivariate analysis, base deficit and bicarbonate were independently related to death or morbidity. CONCLUSION: Our data suggest that "pathologic" fetal acidemia is indicated by an umbilical artery pH <7.00 with a metabolic component. The metabolic component of fetal acidemia (ie, base deficit and bicarbonate) is the most important variable in subsequent neonatal morbidity. As expected, the umbilical artery PO (2) has no apparent clinical utility. The ability to predict more accurately which newborn infants with fetal acidemia are at risk of having complications may lead to a more efficient implementation of preventive measures.

Clinical chorioamnionitis and the prognosis for very low birth weight infants.

OBJECTIVE: To determine the effects of clinical chorioamnionitis on neonatal morbidity and mortality in very low birth weight infants. METHODS: This was an observational cohort analysis of all singleton live-born infants weighing 500-1500 g at 24 weeks' or greater gestational age and born between 1988 and 1996 at Parkland Memorial Hospital, Dallas, Texas. Chorioamnionitis was diagnosed on the basis of maternal fever of 38C with supporting clinical evidence, which included fetal tachycardia, uterine tenderness, and/or malodorous infant, and the absence of another source of infection. Multiple logistic regression analysis was used to adjust for outcomes of interest. RESULTS: Ninety-five of 1367 very low birth weight infants (7%) were exposed to chorioamnionitis. Neonatal sepsis, respiratory distress syndrome, seizure in the first 24 hours of life, intraventricular hemorrhage (grade 3 or 4), and periventricular leukomalacia were all significantly increased with chorioamnionitis, after adjusting for preterm ruptured membranes, pregnancy-associated hypertension, cesarean birth, gestational age, and birth weight. The odds ratios for intraventricular hemorrhage, periventricular leukomalacia, and seizures in the first 24 hours were 2.8 (95% confidence interval [CI] 1.6, 4.8), 3.4 (95% CI 1.6, 7.3), and 2.9 (95% CI 1.2, 6.8), respectively. CONCLUSION: Our results suggest a link between clinical chorioamnionitis and several indices of neonatal morbidity in the very low birth weight infant. Chorioamnionitis appears to make the very low birth weight infant particularly vulnerable to neurologic damage.

The relationship of infection to method of delivery in twin pregnancy.

OBJECTIVE: Our purpose was to determine whether manipulation of the second twin increases the risk of postpartum infection. STUDY DESIGN: Medical records of all twin deliveries between January 1991 and December 1994 were reviewed. The route of delivery (vaginal vs cesarean section) was examined. The vaginal group was further divided into those delivered in the vertex/vertex position (i.e., no uterine manipulation) versus those delivered vertex/breech extraction (i.e., manipulation). The chi 2 and Student t test were used where appropriate. RESULTS: A total of 718 twins were identified, and maternal age, parity, gestational age at delivery (36 weeks), and birth weight (2278 gm) were similar among groups. The metritis rate was higher in the cesarean group (74/447 or 18%) than in the vaginal group (17/299 or 5.7%, p < 0.001). In comparing the vaginal group delivered without uterine manipulation with the vaginal group delivered with manipulation (i.e., breech extraction), there was no difference in the incidence of metritis (10/147 or 6.8% vs 7/152 or 4.6%, not significant). The length of time between delivery of twin A and twin B did not affect the metritis rate. Neonatal outcomes including sepsis, neonatal death, and length of hospitalization were similar among groups (not significant). CONCLUSION: Uterine manipulation of the second twin does not increase the risk of postpartum metritis or neonatal sepsis. In addition, the time interval between delivery of twins A and B has no effect on the rate of metritis. Although the rate of endometritis has been reported to be higher with twins delivered by cesarean section compared to singletons, the 18% rate of endometritis in twins delivered by cesarean section in this study is slightly lower than in our general population of cesarean deliveries (22%).

Outcome of twin gestations with a single anomalous fetus.

OBJECTIVE: Our goal was to determine whether the presence of one anomalous fetus in a twin gestation affects pregnancy outcome when compared with twin pregnancies without fetal anomalies. STUDY DESIGN: Maternal and neonatal data from 970 twin pregnancies delivered from 1988 to 1995 were collected. Three groups of twin gestations were identified: one fetus with a major anomaly (n = 18), one fetus with a minor anomaly (n = 38), and both fetuses without anomalies (n = 914). RESULTS: Maternal demographic characteristics (age, race, and antepartum complications) were similar among the groups. There was no difference in neonatal outcome (gestational age at delivery, birth weight, cord pH, sepsis, and death) in the minor anomaly and no anomaly groups. There were significant differences between the major anomaly group and the no anomaly group in gestational age at delivery (32.9 vs 35.6 weeks, p < 0.05), birth weight at delivery (1759 vs 2291 gm, p < 0.05), hospital days (41 vs 13 days, p < 0.05), and perinatal death of the anomalous fetus (278/1000 vs 10/1000). Except for total days in the hospital, there was no difference in neonatal morbidity or mortality for the normal fetus when compared with the minor group or the no anomaly group. CONCLUSION: The presence of a fetus with a major anomaly in a twin gestation increases the risk of preterm delivery. The neonatal outcome of the nonanomalous fetus does not appear to be affected by the anomalous fetus.

Antibiotic use in pregnancy.

With a few notable exceptions, most antibiotics can be used with relative safety during pregnancy. Moreover, none of the antibiotics to date has been shown to be teratogenic, although tetracycline may cause yellow-brown discoloration of the deciduous teeth (a fetal effect). Thus, antibiotics should not be withheld from the pregnant woman, especially when indicated for serious, life-threatening infections.

Anticoagulants and thrombolytics during pregnancy.

Although venous thromboembolism is a rare complication of pregnancy, it is one of the leading causes of maternal mortality. As many as 40% of asymptomatic women with deep venous thrombosis may indeed have a pulmonary embolism. Therefore, pregnant women with thromboembolic disease, a history of thromboembolic disease, or those who are at increased risk of thromboembolism (mechanical cardiac valve prostheses, antithrombin II, or protein C or S deficient) should receive anticoagulant therapy. The choice of anticoagulant therapy in a pregnant woman as well as the dose and duration will depend on the specific condition being treated. Although anticoagulant therapy is beneficial, it is not without risks to both mother and fetus. This article discusses the use of anticoagulants and thrombolytics in pregnant women.

The maternal-fetal transfer of lamivudine in the ex vivo human placenta.

OBJECTIVE: Our purpose was to measure the transfer of lamivudine ([-]-2'-deoxy-3'-thiacytidine) across the human placenta both alone and in the presence of zidovudine. STUDY DESIGN: Nine placentas from term, elective cesarean deliveries were analyzed with use of the ex vivo single cotyledon perfusion system. Antipyrine was used as the reference compound to measure the clearance index values of lamivudine alone and in combination with zidovudine. Lamivudine concentrations in the perfusates and tissues were quantified by high-pressure liquid chromatography. RESULTS: The clearance index of lamivudine at a maternal concentration of 1.39 micrograms/ml was 0.23 +/- 0.14. At a peak concentration of 14.68 micrograms/ml the clearance index was 0.14 +/- 0.06. These index values did not significantly change in the presence of 1 or 10 micrograms/ml of zidovudine. In a closed recirculating system the fetal lamivudine concentration increased as more lamivudine was added to the maternal perfusate. The addition of zidovudine did not influence this transfer. CONCLUSION: Lamivudine appears to cross the placenta by simple diffusion and its transfer does not appear to be altered by zidovudine.

Ampicillin for neonatal group B streptococcal prophylaxis: how rapidly can bactericidal concentrations be achieved?

OBJECTIVE: Our purpose was to determine how rapidly bactericidal concentrations of ampicillin against group B streptococci are achieved in amniotic fluid and cord blood after a 2 gm maternal infusion. STUDY DESIGN: Ampicillin was administered at varying time intervals between 3 and 67 minutes before elective cesarean delivery in 40 women. Samples of amniotic fluid were obtained by amniocentesis just before the uterine incision was made. Umbilical and maternal blood were obtained at the time of delivery. Ampicillin concentrations were measured by high-pressure liquid chromatography. RESULTS: The mean concentrations of ampicillin measured in maternal and umbilical cord sera all exceeded the minimum bactericidal concentrations reported for group B streptococci (0.25 to 2.0 micrograms/ml) and were achieved as soon as 5 minutes after ampicillin infusion. Similarly, bactericidal levels of ampicillin in the amniotic fluid could be detected as early as 5 minutes. However, such concentrations of ampicillin in the amniotic fluid were achieved in only 85% of the pregnancies studied. CONCLUSIONS: Bactericidal levels of ampicillin against group B streptococci can usually be achieved rapidly in both fetal blood and amniotic fluid after a standard 2 gm intravenous dose given to the mother for neonatal prophylaxis.

Fetal effects of prophylactic ephedrine and maternal hypotension during regional anesthesia for cesarean section.

The purpose of this study was to evaluate the effects of a prophylactic intravenous bolus of ephedrine on the incidence and severity of maternal hypotension and on neonatal outcome. Term healthy parturients (n = 122) scheduled for elective repeat cesarean section under regional anesthesia were studied. Ninety-two women received 10 mg ephedrine as a prophylactic intravenous bolus prior to intrathecal epidural local anesthesia. Thirty parturients who served as controls did not receive prophylactic ephedrine. Maternal blood pressures, Apgar scores, and umbilical cord blood acid-base status were evaluated. Sixty-three of 92 women (69%) who received intravenous prophylactic ephedrine prior to regional anesthesia developed hypotension compared to 21 (70%) controls. The mean (+/- SD) lowest systolic blood pressure was similar in both groups (95.6 +/- 12.9 vs. 96 +/- 8.9 mmHg; P = 0.86). The mean (+/-SD) fetal pH was significantly lower with prophylactic ephedrine than controls (7.24 +/- 0.07 vs. 7.28 +/- 0.05; P = 0.001). The frequency of umbilical artery blood pH < 7.20 was 10.6% for the ephedrine group vs. 3.2% for controls (P = 0.024). Among newborns of hypotensive mothers, the frequency of umbilical artery blood pH < 7.20 was 30.2% and 4.6% for the ephedrine and control groups, respectively (P = 0.018). Intravenous prophylaxis with ephedrine did not significantly decrease the frequency of hypotension in women receiving regional anesthesia and resulted in a greater proportion of umbilical artery blood pH values < 7.20.

Management of disseminated intravascular coagulopathy.

Disseminated intravascular coagulopathy is a process in which aberrant activation of the clotting mechanism results in defective coagulation. Although infrequently encountered during pregnancy, disseminated intravascular coagulopathy is associated with several clinical situations unique to obstetrics. Management consists of treating the underlying cause, restoring and maintaining the circulating blood volume, and replacing deficient clotting factors as indicated.

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid.

OBJECTIVE: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. STUDY DESIGN: Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate matter (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients were also used. RESULTS: There were no significant differences in mean umbilical artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs 30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/- 6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. CONCLUSIONS: There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.

Erythropoietin use in pregnancy: two cases and a review of the literature.

End-stage renal disease complicates only a small percentage of pregnancies, but, of these, virtually all become anemic due to a deficiency in erythropoietin. Erythropoietin has been shown to correct anemia due to renal disease in nonpregnant patients. We report two cases of erythropoietin use during pregnancy complicated by severe anemia due to renal failure. No maternal or fetal side effects were noted. Our two cases exemplify that erythropoietin is an effective means of treating anemia due to renal disease in the gravid patient.