The role of Doppler studies in predicting individual intrauterine fetal demise after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To investigate the role of Doppler studies in predicting individual fetal demise in patients scheduled for selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS). METHODS: Doppler studies of the umbilical artery, umbilical vein, ductus venosus, tricuspid valve regurgitation and middle cerebral artery were performed in the donor and recipient twins before and 24 hours after SLPCV. Results were analyzed cross-sectionally and longitudinally. As multiple comparisons were made, an a priori alpha rejection was set at P < 0.001. RESULTS: One hundred and ten consecutive patients were available for analysis. Overall fetal survival was 68.6% (151/220) with at least one survivor in 88.2% (97/110) of cases. Absent or reversed end-diastolic velocity in the umbilical artery of the donor twin was the only preoperative Doppler result predictive of intrauterine fetal demise (IUFD) (10/15, 66.7%, P < 0.001). Postoperatively, reversed flow during atrial contraction in the ductus venosus of the donor twin showed a trend towards prediction of IUFD of this fetus (4/5, 80%, P = 0.007). No other Doppler studies, including the longitudinal analyses, were predictive of IUFD. CONCLUSIONS: Our data suggest that preoperative absent or reversed end-diastolic velocity in the umbilical artery may be useful in predicting individual fetal demise of the donor twin in TTTS patients scheduled for SLPCV. This may reflect the role of decreased individual placental mass that may be associated with some donor twins. The inability of other Doppler studies to predict individual IUFD may be explained preoperatively by the effect of the interfetal vascular connections on the individual Doppler signals and postoperatively by the effect of surgery or the timing of the assessment. Our findings may be important in patient counseling, in furthering understanding of the disease, and perhaps in improving surgical technique.

Selective photocoagulation of communicating vessels in the treatment of monochorionic twins with selective growth retardation.

OBJECTIVE: Current treatment of patients with selective intrauterine growth retardation in monochorionic twins includes expectant management, termination of pregnancy, or umbilical-cord occlusion. The purpose of this study was to assess the outcome of monochorionic twins with selective intrauterine growth retardation who were treated with selective laser photocoagulation of the communicating vessels. STUDY DESIGN: Monochorionic twin pregnancies with selective intrauterine growth retardation at less than 26 weeks were eligible for the study. Selective intrauterine growth retardation was defined as <10th percentile for gestational age. Absent or reverse end-diastolic velocity in the umbilical artery of the twin with selective intrauterine growth retardation was required for eligibility after January 2000. RESULTS: Thirty patients met the criteria for the study: 17 patients were treated expectantly (group I); 2 patients underwent umbilical-cord ligation of the twin with selective intrauterine growth retardation, and 11 patients underwent selective laser photocoagulation of the communicating vessels (group II). Survival rates for at least 1 fetus were no different between groups I and II (14/17 [82.3%] vs 8/11 [72.3%]; P = .4). However, concomitant demise of the co-twin occurred in 4 of 7 patients, and iatrogenic premature delivery for deterioration of the twin with selective intrauterine growth retardation was necessary in 2 patients in group I, which resulted in significant neonatal morbidity. Of the live-born babies, neurologic handicap was present in 3 of 22 babies (13.6%) versus 0 of 12 in groups I and II, respectively (P < .0001). CONCLUSION: Selective intrauterine growth retardation in monochorionic twins can be effectively treated with selective laser photocoagulation of the communicating vessels. By unlinking the circulations between the fetuses, the pregnancy is rendered "functionally" dichorionic, which improves pregnancy treatment and results in decreased neonatal morbidity. This approach constitutes a new valuable alternative in the treatment of monochorionic twin pregnancies with selective intrauterine growth retardation. A randomized clinical trial of expectant treatment versus selective laser photocoagulation of the communicating vessels for monochorionic selective intrauterine growth retardation can be considered.

Ultrasound prenatal diagnosis of fetus in fetu.

A case of fetus in fetu was diagnosed prenatally using ultrasound. The differential diagnosis between a fetus in fetu and a highly differentiated teratoma is discussed. The importance of prenatal diagnosis of fetus in fetu and the effect on subsequent management are described.

Fetal hydrolaparoscopy and endoscopic cystotomy in complicated cases of lower urinary tract obstruction.

OBJECTIVE: Vesicoamniotic shunting may be difficult or impossible in selected cases of fetal lower obstructive uropathy. The purpose of this article is to describe the performance of fetal hydrolaparoscopy and endoscopic fetal cystotomy in two fetuses with complicated lower obstructive uropathy. STUDY DESIGN: Fetal hydrolaparoscopy-endoscopic fetal cystotomy was performed in a patient with a markedly thickened bladder that could not be entered percutaneously. A peritoneoamniotic (bridge) shunt was also placed. Fetal hydrolaparoscopy-endoscopic fetal cystotomy was performed in a second patient with a collapsed bladder from a previous vesicocentesis, because vesicoinfusion resulted in further ascites. Fetal cystoscopy was performed after endoscopic fetal cystotomy, and posterior urethral valves were ablated with neodymium:yttrium-aluminum-garnet laser energy. A vesicoamniotic shunt was left in place. RESULTS: Adequate bladder drainage was obtained in both cases. The first baby required bilateral nephrotomy and a permanent cystotomy at birth and is scheduled for a bladder expansion procedure at the age of year. The second patient had premature rupture of membranes and fetal death from treatment of this complication 5 days after the original procedure. CONCLUSION: Fetal hydrolaparoscopy-endoscopic fetal cystotomy can be performed in complicated cases of lower obstructive uropathy. The procedure involves the creation of a defect in the bladder dome under direct endoscopic visualization within a spontaneous or intentional hydroperitoneum. Peritoneoamniotic shunting, vesicoamniotic shunting, or ablation of posterior urethral valves may then be performed. Fetal hydrolaparoscopy-endoscopic fetal cystotomy should be reserved only for complicated cases of lower obstructive uropathy in which conventional vesicoamniotic shunting is not safely possible. Further experience with fetal hydrolaparoscopy-endoscopic fetal cystotomy is necessary to establish its risks and benefits.

In utero diagnosis of trichothiodystrophy by endoscopically-guided fetal eyebrow biopsy.

OBJECTIVE: To describe the prenatal diagnosis of trichothiodystrophy (TTD) through endoscopically-guided fetal eyebrow biopsy. MATERIALS AND METHODS: A 32-year-old patient, gravida 4, para 3, with a history of 2 previous infants affected with TTD was referred at 17(5)/(7) weeks for fetal hair biopsy. DNA repair studies had been normal in the previous children. Four 1-mm biopsies were obtained from the external aspect of the fetal eyebrows under direct endoscopic guidance. Fetal hair samples were assessed with polarized microscopy, electron microscopy, hematoxylin and eosin staining, and were also sent for analysis of sulfur content (cystine levels). RESULTS: The fetal eyebrows were the only adequate source of hair in the early second trimester. The biopsy samples yielded adequate material for all tests. Polarized microscopy showed characteristic banding patterns, but trichoschisis was not apparent. Cystine levels (19 micromol/l) in the biopsy sample were significantly lower than an age-matched (fresh spontaneous abortion) control (368 micromol/l). CONCLUSION: Prenatal diagnosis of TTD is possible in the second trimester through endoscopically-guided eyebrow biopsy. An adequate amount of hair is present in the eyebrows by then, and the disease is already manifest. Analysis of sulfur content of the hair samples is preferred over polarized or electron microscopy, as many classic microscopic findings of TTD may not be present in the early second trimester.

Treatment of iatrogenic previable premature rupture of membranes with intra-amniotic injection of platelets and cryoprecipitate (amniopatch): preliminary experience.

OBJECTIVE: Our aim was to describe the treatment of iatrogenic previable premature rupture of membranes with the intra-amniotic injection of platelets and cryoprecipitate (amniopatch). STUDY DESIGN: Patients with iatrogenic previable premature rupture of membranes and without evidence of intra-amniotic infection underwent transabdominal intra-amniotic injection of platelets and cryoprecipitate through a 22-gauge needle. The study was approved by the Institutional Review Board of St Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Seven patients with iatrogenic preterm premature rupture of membranes underwent placement of an amniopatch. Membrane sealing was verifiable in 6 of 7 patients. Three patients had iatrogenic preterm premature rupture of membranes after operative fetoscopy, 3 cases were after genetic amniocentesis, and 1 was after diagnostic fetoscopy. Three pregnancies progressed well, with restoration of the amniotic fluid volume and no further leakage. Two patients had unexplained fetal death despite successful sealing. One case of bladder outlet obstruction had no further leakage, but oligohydramnios persisted and did not allow unequivocal documentation of sealing. One patient miscarried from twin-twin transfusion, but the amniotic cavity was sealed. CONCLUSIONS: Iatrogenic preterm premature rupture of membranes can be treated effectively with an amniopatch. The technique is simple and does not require knowledge of the exact location of the defect. Unexpected fetal death from the procedure may be attributable to vasoactive effects of platelets or indigo carmine. Although the appropriate dose of platelets and cryoprecipitate needs to be established, the amniopatch may mean that iatrogenic preterm premature rupture of membranes no longer needs to be considered a devastating complication of pregnancy.

Aggressive perinatal care for high-order multiple gestations: Does good perinatal outcome justify aggressive assisted reproductive techniques?

OBJECTIVE: The purpose of this study was to determine the factors that must be considered for appropriate counseling of patients with high-order multiple gestations. STUDY DESIGN: A retrospective chart review was carried out from all high-order multiple gestations that were managed by a single perinatology group from February 1993-June 1998. Twin pregnancies that did not result from fetal reduction procedures were used as a control group. RESULTS: Clinical outcome data were analyzed from 9 quadruplet, 25 triplet, 19 reduced twin, and 24 nonreduced twin pregnancies. Women with quadruplet pregnancies were admitted more frequently at an early gestational age, the infants were delivered earlier, and the maternal and neonatal hospital days were longer than for triplet and reduced and nonreduced twin gestations. Triplet pregnancies had an earlier gestational age at delivery (32.3 vs 34.2 weeks), a higher incidence of preterm labor (87% vs 68%), and a higher percentage of neonatal intensive care unit admissions (94% vs 59%) than reduced twin gestations. Reduced twins were hospitalized longer (16.4 vs 9.8 days), were delivered earlier (34.2 vs 36.2 weeks), had a higher incidence of preterm labor (68% vs 29%), and had a greater percentage of neonatal intensive care unit admissions (59% vs 21%), a greater percentage of birth weight <1500 g, and a greater frequency of respiratory distress syndrome (16% vs 2%) than nonreduced twins. There was no difference in neonatal survival and neurologic morbidity when all groups were compared. CONCLUSION: Although early delivery and prolonged (maternal and neonatal) hospitalization were common with quadruplets and triplets, maternal and neonatal outcomes were excellent. The decision for reduction from triplets to twins may not necessarily change pregnancy outcome but should still be discussed as an option for the parents. Continued efforts need to be made to reduce the overall number of iatrogenic high-order multiple gestations.

Change in antibiotic resistance of group B streptococcus: impact on intrapartum management.

OBJECTIVE: Intrapartum chemoprophylaxis has resulted in a significant reduction of group B Streptococcus neonatal infection. For penicillin-allergic patients, clindamycin or erythromycin is the recommended antibiotic. The purpose of this study was to establish any pattern of antibiotic resistance of group B streptococcal clinical isolates over the past 15 years. STUDY DESIGN: Group B streptococcal isolates obtained from the lower genital tract were tested for sensitivity to ampicillin, penicillin, clindamycin, and erythromycin. The sensitivity of 100 group B streptococcal isolates retrieved in the period 1997-1998 was compared with that of 85 group B streptococcal isolates from 1980-1993. RESULTS: From 1980-1993 group B streptococcal isolates were available for testing for antibiotic resistance along with 100 isolates from a second study period 1997-1998. Of the 100 group B streptococcal isolates from 1997-1998, 18 were resistant to erythromycin, of which 5 were also resistant to clindamycin, as compared with 1 of the 85 isolates from 1980-1993 that was resistant to erythromycin (P <.001). All the isolates were sensitive to ampicillin and penicillin. All 18 resistant strains from 1997-1998 were found to be sensitive to cephalothin. CONCLUSION: Over the past 18 years there has been increased in vitro resistance of group B streptococci to both clindamycin and erythromycin. If other studies confirm these findings, modifications to the current Centers for Disease Control and Prevention recommendations may be necessary.

Staging of twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of sonographic and clinical parameters to develop a staging classification of twin-twin transfusion syndrome (TTTS). STUDY DESIGN: Severe TTTS was defined as the presence of polyhydramnios (maximum vertical pocket of > or = 8 cm) and oligohydramnios (maximum vertical pocket of < or = 2 cm). Nonvisualization of the bladder in the donor twin (-BDT) and absence of presence of hydrops was also noted. The middle cerebral artery, umbilical artery, ductus venosus, and umbilical vein in both fetuses were assessed with pulsed Doppler. Critically abnormal Doppler studies (CADs) were defined as absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein. TTTS was staged as follows: stage I, BDT still visible; stage II, BDT no longer visible, no CADs; stage III, CADs; stage IV, hydrops; stage V, demise of one or both twins. Laser photocoagulation of communicating vessels (LPCV) or umbilical cord ligation was performed depending on the severity of the condition. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa and by the Fetal Therapy Board at Hutzel Hospital, Detroit, and all patients gave informed consent. RESULTS: A total of 80 of 108 referred patients met criteria for surgery, but only 65 were treated surgically: 48 with LPCV and 17 with umbilical cord ligation. Complete Doppler data were obtainable in 41 of 48 LPCV patients. Survival rates by stage for one or two fetuses were statistically different (chi-squared analysis = 12.9, df = 6, p = 0.044). Neither percent size discordance nor gestational age at diagnosis were predictive of outcome. CONCLUSION: Staging of TTTS using the proposed criteria has prognostic significance. This staging system may allow comparison of outcome data of TTTS with different treatment modalities.

Transabdominal intra-amniotic endoscopic assessment of previable premature rupture of membranes.

OBJECTIVE: Our purpose was to describe the endoscopic characteristics of the site of rupture in vivo in patients with spontaneous premature rupture of membranes. STUDY DESIGN: Patients with preterm premature rupture of membranes between 16 and 26 weeks of gestation, without evidence of intra-amniotic infection, and with a normal karyotype underwent transabdominal endoscopic examination of the amniotic cavity. Subsequently, an amniopatch of a combination of platelets and cryoprecipitate to seal the membrane defect was administered. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Four patients underwent endoscopic examination and amniopatch administration; three had spontaneous preterm premature rupture of membranes, and in the other the membranes ruptured after an early amniocentesis. The location of the site of rupture was over the internal os in the 3 cases with spontaneous preterm premature rupture of membranes. This area was normal in the patient with iatrogenic preterm premature rupture of membranes. The longer the time between preterm premature rupture of membranes and fetoscopy, the larger and less defined was the site of rupture. The amniopatch restored amniotic integrity for a maximum of 72 hours. CONCLUSIONS: This is the first in vivo endoscopic visualization of the site of spontaneous rupture of membranes from within the uterine cavity. The defect is located over the internal cervical os in patients with spontaneous preterm premature rupture of membranes. There appear to be time-related changes in the morphologic characteristics of the site of rupture. Endoscopic visualization of the site of rupture has the potential for improving our understanding of spontaneous preterm premature rupture of membranes and in the development of possible therapeutic alternatives.

In utero lysis of amniotic bands.

Amniotic band syndrome is a sporadic condition that occurs in approximately 1:1200 to 1:15,000 live births and that may result in amputations, constrictions and other deformities of the fetus. Although some cases present with congenital anomalies that are beyond surgical repair, a selected group of fetuses may show isolated limb constriction. It has been speculated that, without treatment, amputation or severe dysfunction of the limb may occur. Despite these potential complications, surgical treatment for this selected group of fetuses has not been previously performed. We report two cases that were successfully treated using novel minimally invasive surgical techniques. The cases involved fetuses with amniotic band syndrome with associated limb constriction in which the amniotic band was surgically interrupted to avoid spontaneous amputation of the extremity. Adequate blood flow distal to the obstruction was preserved and significant functional improvement of the extremity occurred in both cases, preserving the limbs. These cases represent the first prenatal surgical intervention successfully used to treat constricting amniotic bands in humans. In addition, these cases represent the first time that a non-lethal fetal entity has been surgically treated in utero. The results of this innovative therapy will encourage the efforts to continue developing minimally invasive techniques for the correction of birth defects.

Obstetric management of incompetent cervix and bulging fetal membranes.

OBJECTIVE: To evaluate the effect of emergency cerclage on perinatal outcome in patients with incompetent cervix. STUDY DESIGN: In this descriptive retrospective study, the charts of all patients admitted from 1985 to 1992 with a diagnosis of incompetent cervix and cervical dilatation > or = 2 cm were reviewed. Cervical dilatation at the time of cerclage placement, subsequent pregnancy duration and neonatal outcome were analyzed. Statistical analysis was performed using the paired Student t test. RESULTS: During the eight-year period, 42 patients were admitted with a diagnosis of incompetent cervix, cervical dilatation > or = 2 cm, and underwent emergency cerclage. Cerclage resulted in a median (range) continuation of pregnancy of 30 (2-102) days. In 20 of these patients the membranes were not bulging through the external cervical os, and pregnancy was extended a median of 50 (30-102) days. The remaining 22 patients presented with membranes bulging into the vagina, and emergency cervical cerclage resulted in a median pregnancy extension of 16 (2-98) days. Parturients with bulging membranes were then analyzed according to cervical dilatation. Cerclage success was significantly lower when attempted at a cervical dilation > or = 4 cm. Median pregnancy duration was 6 (2-15) versus 21 (5-98) days in patients with cervical dilatation < 4 cm. CONCLUSION: The results of this study support emergency cerclage in patients without bulging membranes. The data do not support the use of emergency cervical cerclage in patients with bulging membranes and dilatation > or = 4 cm. In those patients, the use of cerclage should be individualized.

Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study.

OBJECTIVE: Our purpose was to determine whether treatment of bacterial vaginosis with metronidazole in patients with preterm delivery in the penultimate pregnancy from preterm labor or premature rupture of membranes reduces the risk of subsequent preterm birth. STUDY DESIGN: From January 1989 to June 1992 patients with a singleton gestation between 13 and 20 weeks and a history of preterm birth in the preceding pregnancy from either idiopathic preterm labor or premature rupture of membranes were screened for bacterial vaginosis. Those with a positive screen were randomized to receive 250 mg of metronidazole three times a day for 7 days or placebo in a double-blind design. Data were analyzed with Student t and chi 2 tests, and differences considered significant at p < 0.05. RESULTS: Of 94 eligible patients, 80 were enrolled and completed the study, of which 44 received metronidazole. Both groups were comparable in number of entry variables. Compared with the placebo group, patients in the metronidazole group had significantly fewer hospital admissions for preterm labor, 12 (27%) versus 28 (78%); preterm births, eight (18%) versus 16 (39%); births of infants weighing < 2500 gm, six (14%) versus 12 (33%); and premature rupture of membranes, two (5%) versus 12 (33%). CONCLUSION: Treatment of bacterial vaginosis with metronidazole was effective in reducing preterm births in patients with a history of prematurity in the preceding pregnancy.

Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study.

OBJECTIVE: Our purpose was to establish the efficacy and safety of nifedipine versus magnesium sulfate in arresting preterm labor and the efficacy of nifedipine versus terbutaline in preventing recurrent labor. STUDY DESIGN: Singleton pregnancies at < 34 weeks in preterm labor were randomized to either oral nifedipine or intravenous magnesium sulfate. In case of tocolysis failure ritodrine was added. After labor was arrested, the patients in the nifedipine group were maintained on oral nifedipine, and those in the magnesium sulfate group were treated with oral terbutaline until completing 34 weeks. RESULTS: Of 100 patients 80 were considered eligible, of whom 39 were randomized to the nifedipine group. Both groups were comparable in terms of a number of entry variables, including cervical examination, contraction frequency, and gestational age. Both drugs were equally effective in arresting labor and delaying delivery > 48 hours, 92% versus 93%. Both study groups had a similar incidence of side effects, although four (10%) of magnesium sulfate-treated patients required drug discontinuation because of severe symptoms. Nifedipine was as effective as terbutaline in preventing recurrent labor, 26% versus 24%, and in achieving a gestation > 34 weeks, 62% versus 68%. CONCLUSIONS: Oral nifedipine is as effective as magnesium sulfate and terbutaline in arresting and preventing idiopathic preterm labor.

Preparing the fetus for preterm birth.

Optimum perinatal outcome is only achieved by the prevention of premature birth. When preterm delivery is unavoidable, antenatal pharmacologic therapy will result in a reduction in the leading causes of neonatal morbidity and mortality, mainly respiratory distress syndrome (RDS), BPD, intraventricular haemorrhage (IVH) and sepsis. These treatments combined with meticulous intrapartum management will result in significant improvements in the neonatal and long-term outcome in the premature baby.

Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study.

OBJECTIVE: Our purpose was to evaluate the relative efficacy and safety of indomethacin versus magnesium sulfate in the management of preterm labor in pregnancies < 32 weeks of gestation. STUDY DESIGN: Eligible patients admitted with singleton pregnancies and idiopathic preterm labor between August 1988 and October 1989 were randomized by sealed envelopes to receive either indomethacin or intravenous magnesium sulfate. RESULTS: Of 101 eligible patients 49 were randomized to receive indomethacin. The two study groups were similar in regard to a number of entry variables, including gestational age, cervical examination, and contraction frequency. Indomethacin was as effective as magnesium sulfate in delaying delivery > 48 hours, 90% versus 85%, and together with oral terbutaline in extending the gestation, 22.9 versus 22.7 days. Tocolysis with magnesium sulfate was discontinued in eight (15%) patients because of maternal side effects, in contrast to none in the indomethacin group, p < 0.05. CONCLUSION: For gestations < 32 weeks indomethacin may be considered an appropriate alternative to magnesium sulfate as a first-time tocolytic agent.

Acute epiglottitis during pregnancy.

A 26-year-old woman in her third trimester of pregnancy had stridor. Epiglottitis was diagnosed by fiberoptic laryngoscopy. Staphylococcus aureus was the predominant organism isolated from the laryngeal aspirate. Early intubation proved effective in managing this potentially life-threatening disease. Although pharyngitis is the most common cause of sore throat in the adult, acute epiglottitis must be considered in the differential diagnosis when there is unrelenting throat pain and minimal objective signs of pharyngitis. An early diagnosis with aggressive airway management can be life saving to both mother and fetus.

Premature rupture of membranes at < 25 weeks: a management dilemma.

OBJECTIVE: A retrospective study was conducted to establish the perinatal and long-term neonatal outcome at 1 year of life (corrected) of pregnancies complicated by premature rupture of membranes before fetal viability. STUDY DESIGN: The outcome of 94 singleton pregnancies admitted from June 1982 to June 1991 with premature rupture of membranes at < 25 weeks' gestation that were managed expectantly were studied. To establish the effect of rupture of membranes, the neonatal outcomes of babies born with birth weights > 500 gm and gestational ages > 24 weeks were compared with those of a similar group of neonates from patients without preterm rupture of membranes and matched by gestational age, birth weight, race, sex, and mode of delivery. The outcome of the surviving neonates at 1 year of life (corrected) was established on the basis of their Bailey mental and psychomotor scores and on the results of neurologic, ophthalmologic, and hearing examinations. RESULTS: The overall incidence of amnionitis was 24%. The median latency period was 10.5 days; in 26% of patients delivery was delayed > 2 weeks. Pulmonary hypoplasia was detected in 5% of patients, and there was no evidence of orthopedic deformities. Survival was achieved in 39 (40%) of neonates; 63% of these survivors were considered to have had normal development at 1 year of life (corrected). CONCLUSION: Premature rupture of membranes at < 25 weeks is associated with a relatively high risk of perinatal mortality and neonatal and long-term morbidity, but a successful outcome can be achieved in about 60% of survivors.

Antenatal therapy to minimize neonatal intraventricular hemorrhage.

Periventricular-intraventricular hemorrhage is an important problem, resulting in significant mortality and morbidity. Attempts to reduce this complication require an understanding of its pathogenesis. In this chapter a model was proposed, consisting of a series of events resulting in rapid changes of cerebral blood flow and intracranial pressure and leading to rupture of the unique fragile vessels of the germinal matrix and intraventricular regions. Understanding the beneficial physiologic changes induced by such agents such as phenobarbital and vitamin K and that such pharmacologic therapy must be started during the antenatal period has resulted in significant reductions of severe grades of IVH. Further prospective studies are needed to confirm these results using these two drugs alone and in combination. Other potentially beneficial drugs such as indomethacin should be investigated. Although the benefits of such therapy may improve perinatal outcome, the emphasis in our discipline should be the continued attempt to prevent the delivery of these VLBW infants.