Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.

Based on past studies of an experimental model of severe intrauterine pulmonary hypertension, we hypothesized that endothelin-1 (ET-1) contributes to high pulmonary vascular resistance (PVR), hypertensive lung structural changes, and right ventricular hypertrophy (RVH) caused by prolonged closure of the ductus arteriosus. To test this hypothesis, we studied the effects of BQ 123, a selective ET(A) receptor antagonist, after ligation of the ductus arteriosus in utero. In 19 late gestation fetal lambs (126+/-3 d; 147 d, term) we ligated the ductus arteriosus at surgery, and treated animals with either BQ 123 (1 mg/d) or vehicle (0.1% DMSO, HTN) in the pulmonary artery for 8 d. Chronic BQ 123 treatment attenuated the rise in mean pulmonary artery pressure (PAP) 8 d after ductus arteriosus ligation (78+/-2, HTN vs. 70+/-4 mmHg, BQ 123, P < 0.05). To study the effects of ET(A) blockade at birth, 15 animals were delivered by cesarean section and ventilated with 10% oxygen (O2), 100% O2 and inhaled nitric oxide (NO). Lambs treated with BQ 123 had lower PVR after delivery during ventilation with 10% O2, 100% O2, and inhaled NO (HTN vs. BQ 123, P < 0.05 for each intervention). Acute BQ 123 treatment (2 mg/30 min) lowered PVR in three HTN animals ventilated with 100% O2 and inhaled NO (P < 0.05). Chronic BQ 123 treatment prevented the development of RVH as determined by the ratio of the right ventricle/left ventricle + septum (0.79+/-0.03, HTN vs. 0.57+/-0.06, BQ 123, P < 0.05) and attenuated the increase in wall thickness of small pulmonary arteries (61+/-2, HTN vs. 50+/-2%, BQ 123, P < 0.05). In summary, chronic intrauterine ET(A) receptor blockade decreased PAP in utero, decreased RVH and distal muscularization of small pulmonary arteries, and increased the fall in PVR at delivery. We conclude that ET(A) receptor stimulation contributes to the pathogenesis and pathophysiology of experimental perinatal pulmonary hypertension.

Development and mechanisms of fetal hypoxia in severe fetal growth restriction.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O(2) uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for 12h; approximately 35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All ewes were then placed in a control environment ( approximately 21 degrees C, 24h; approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p<0.0001), umbilical O(2) uptake/kg fetus was 76% of C (p<0.01) and umbilical venous PO(2) was reduced (20.2 vs. 29.7 Torr, p<0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs. 23 Torr, p<0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O(2) uptake.

Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study.

OBJECTIVE: The objective of this study is to estimate associations between changes in maternal arterial pressure during normotensive pregnancies and offspring birth weight and body composition at birth. STUDY DESIGN: Prospective study of 762 pregnant normotensive Colorado women, recruited from outpatient obstetrics clinics. Repeated arterial pressure measurements during pregnancy were averaged within the second and third trimesters, respectively. Multivariable regression models estimated associations between second to third trimester changes in arterial pressure and small-for-gestational-age birth weight, fat mass, fat-free mass and percent body fat. RESULTS: A greater second to third trimester increase in maternal arterial pressure was associated with greater odds of small-for-gestational-age birth weight. Greater increases in maternal diastolic blood pressure were associated with reductions in offspring percent body fat (-1.1% in highest vs lowest quartile of increase, 95% confidence interval: -1.9%, -0.3%). CONCLUSION: Mid-to-late pregnancy increases in maternal arterial pressure, which do not meet clinical thresholds for hypertension are associated with neonatal body size and composition.

Early initiation of low-dose aspirin for reduction in preeclampsia risk in high-risk women: a secondary analysis of the MFMU High-Risk Aspirin Study.

OBJECTIVE: Early initiation of low-dose aspirin (LDA) may reduce preeclampsia risk. We sought to determine whether LDA was beneficial when initiated <17w0d, within a trial of high-risk women enrolled <26w0d. STUDY DESIGN: Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin study, including women enrolled <17w0d, randomized to LDA (60 mg day(-1)) or placebo with chronic hypertension (CHTN, n=186), diabetes (n=191) or prior preeclampsia (n=146). The primary outcome was preeclampsia at any time in pregnancy, secondary outcomes were early preeclampsia (<34w0d), late preeclampsia (⩾34w), small for gestational age (SGA; neonatal birthweight <10th %) and composite (early preeclampsia or SGA). Outcomes were compared by exact Χ(2)-tests. RESULTS: Baseline characteristics were similar between treatment groups. Aspirin was associated with a lower rate of late-onset preeclampsia ⩾34w (17.36% vs 24.42%, P=0.047), with a 41% reduction in women with CHTN (18.28% vs 31.18%, P=0.041). There were no other significant differences in the outcome. CONCLUSION: Aspirin initiated <17w0d reduced the risk for late-onset preeclampsia by 29% supporting the practice of early initiation of aspirin in high-risk women.

Placental development in normal and compromised pregnancies-- a review.

Intrauterine growth restriction (IUGR) is a significant cause of infant mortality and morbidity. It is now clear that IUGR infants exhibit higher rates of coronary heart disease, type 2-diabetes, hypertension and stroke as adults. Therefore, fetal growth not only impacts the outcome of the perinatal period, but also impacts adult well-being. The etiologies of IUGR are numerous, but are often associated with abnormalities in placental structure and function. The process of implantation and placentation requires the production of a plethora of growth factors, cell-adhesion molecules, extracellular matrix proteins, hormones and transcription factors. Many of these exhibit altered expression within the placenta of IUGR pregnancies. However, it has been difficult to fully assess their role during the development of placental insufficiency (PI) in the human, underscoring the need for animal models. Using an ovine model of PI-IUGR we have observed changes in the expression of vascular endothelial growth factor, placental growth factor, their common receptors, as well as angiopoietin 2 and its receptor, Tie 2. We found that changes in these growth factors can be associated with both acute and chronic changes in placental vascular structure and function. These studies and others are providing needed insight into the developmental chronology of placental insufficiency.

Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR).

Placental development requires adequate and organized interaction of vascular growth factors and their receptors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Both VEGF and PlGF, acting through the tyrosine kinase receptors VEGFR-1 and VEGFR-2, have been implicated in playing a role in ovine placental vascular development. The present studies describe the placental expression of components of the VEGF family at two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Both caruncular and cotyledonary VEGF and PlGF mRNA concentration increased with gestational age (P< 0.05), whereas only cotyledonary VEGF and PlGF protein concentration increased over gestation (P< 0.002). At 55 dpc, VEGF mRNA concentration was elevated in hyperthermic (HT) ewes, compared to control thermoneutral (TN) animals (TN; 0.52+/-0.08 vs HT; 1.27+/-0.17 VEGF/GAPDH, P< 0.001). At 90 dpc, expression of PlGF and VEGF mRNA was not altered by the HT treatment. Both TN cotyledonary VEGFR-1 and VEGFR-2 mRNA expression levels rose significantly over the period studied (P< 0.05 and P< 0.01 respectively). Receptor mRNA concentration in HT cotyledonary tissue was significantly reduced at 90 dpc (VEGFR-1; TN 0.21+/-0.02 vs HT 0.11+/-0.01 VEGFR-1/actin, P< 0.05, VEGFR-2; TN 0.18+/-0.05 vs HT 0.07+/-0.01 VEGFR-2/actin, P< 0.01). Soluble VEGFR-1 (sVEGFR-1) mRNA was not detected in these tissues. These alterations in growth factor and growth factor receptor mRNA expression, as a result of environmental heat stress early in placental development, could impair normal placental vascular development. Furthermore, alterations in VEGF, VEGFR-1 and VEGFR-2 mRNA expression, during the period of maximal placental growth, may contribute to the development of placental insufficiency, and ultimately intrauterine growth restriction.

Effect of intra-amniotic administration of Exosurf in preterm rabbit fetuses.

OBJECTIVE: Currently, treatment of respiratory distress syndrome (RDS) of the preterm newborn incorporates exogenous surfactant administration. Because fetuses make breathing motions, we proposed that intra-amniotic administration of an exogenous surfactant, Exosurf, to the preterm rabbit fetus results in uptake of Exosurf into the lungs and improves pulmonary mechanical properties compared with post-delivery treated and untreated litter mates. METHODS: Ten preterm rabbit fetuses were used in a labeling study. A mixture of iron dextran and Exosurf was given in utero, and the minimum dose required to assure delivery of the mixture into the distal airways was 5 mL. In a lung function study, 30 rabbit pups received either 5 mL Exosurf in utero, 0.2 mL Exosurf post-delivery, or no treatment. Pressure-volume curves, opening pressures, and lung volumes at 50 cm H2O were compared among the three groups. RESULTS: Those rabbit pups receiving Exosurf either in utero or after delivery had significantly better pressure-volume relationships (P less than .001) and lower opening pressures (P less than .005) than the rabbit pups with no treatment. There were no differences between the animals treated intra-amniotically and post-delivery. CONCLUSIONS: Intrauterine administration of exogenous surfactant results in uptake of the surfactant solution into the lungs and alters the pulmonary characteristics of the preterm rabbit pup. Potential adverse effects of this means of surfactant administration must be evaluated further. Intrauterine surfactant delivery may provide an additional means of RDS prophylaxis in the antepartum period.

Cotyledon and binucleate cell nitric oxide synthase expression in an ovine model of fetal growth restriction.

Heat exposure early in ovine pregnancy results in placental insufficiency and intrauterine growth restriction (PI-IUGR). We hypothesized that heat exposure in this model disrupts placental structure and reduces placental endothelial nitric oxide synthase (eNOS) protein expression. We measured eNOS protein content and performed immunohistochemistry for eNOS in placentas from thermoneutral (TN) and hyperthermic (HT) animals killed at midgestation (90 days). Placental histomorphometry was compared between groups. Compared with the TN controls, the HT group showed reduced delivery weights (457 +/- 49 vs. 631 +/- 21 g; P < 0.05) and a trend for reduced placentome weights (288 +/- 61 vs. 554 +/- 122 g; P = 0.09). Cotyledon eNOS protein content was reduced by 50% in the HT group (P < 0.03). eNOS localized similarly to the vascular endothelium and binucleated cells (BNCs) within the trophoblast of both experimental groups. HT cotyledons showed a reduction in the ratio of fetal to maternal stromal tissue (1.36 +/- 0.36 vs. 3.59 +/- 1.2; P< or = 0.03). We conclude that eNOS protein expression is reduced in this model of PI-IUGR and that eNOS localizes to both vascular endothelium and the BNC. We speculate that disruption of normal vascular development and BNC eNOS production and function leads to abnormal placental vascular tone and blood flow in this model of PI-IUGR.

Fetal drug therapy.

As prenatal diagnosis has become more sophisticated, avenues for a variety of intrauterine therapies have been opened. Considerable experience has been gained with surgical and pharmacologic approaches. This article provides a review of intrauterine drug therapy aimed at preventing fetal and neonatal disease and treating existing fetal conditions. The future awaits the exciting applications of intrauterine hematopoietic transplants and genetic therapy.

Acute pelvic inflammatory disease after tubal sterilization. A report of three cases.

Pelvic inflammatory disease (PID) is considered to be rare or nonexistent following tubal sterilization. The purpose of this report is to describe three cases of surgically diagnosed acute PID in women previously sterilized by bilateral tubal ligation who presented over a one-year period. All three patients presented with an acute abdomen, fever and elevated white blood cell count. Our experience suggests that PID following tubal sterilization is more common than previously described and can present a diagnostic dilemma.

Fresh frozen plasma prophylaxis for hereditary angioedema during pregnancy. A case report.

BACKGROUND: Hereditary angioedema (HAE) is an uncommon disorder of the complement system due to a deficiency or dysfunction of the inhibitor of the first component of complement (C1 INH). Clinically, HAE is characterized by episodic abdominal pain or edema of the extremities, face, larynx and vulva. Laryngeal edema is potentially lethal and accounts for mortality rates as high as 30%. Therapy is divided into short-term (fresh frozen plasma) and long-term (antifibrinolytic agents, hormonal therapy) prophylaxis, or acute treatment (epinephrine, steroids, antihistamines). CASE: An 18 year-old, primiparous woman presented with a history of multiple episodes of abdominal pain, swelling of abdomen and extremities. A diagnosis of hereditary angioedema was made based on the patient's and family's history and on decreased levels of C1 INH and complement component 4. Standard prophylactic methods were contraindicated due to potential teratogenic effects. Fresh frozen plasma given twice weekly over 2.5 months resulted in reduction in the number and severity of attacks and allowed successful completion of pregnancy. CONCLUSION: This is the first report of fresh frozen plasma therapy as a means of long-term prophylaxis in a pregnant woman. Fresh frozen plasma may serve as an alternate mode of long-term prophylaxis if the standard agents (antifibrinolytic, hormone) are unsuccessful or contraindicated.

Puerperal cerebral venous thrombosis associated with decreased free protein S: a case report.

BACKGROUND: Cerebral venous thrombosis is a rare event with multiple risk factors. This condition can be associated with a hypercoagulable state, such as that seen with dysfunctional or decreased plasma protein C and protein S. Both plasma proteins are naturally occurring, vitamin K-dependent anticoagulants that are important for regulation of the clotting cascade. CASE: A postpartum patient presented with complaints of a severe headache and hypertension and later developed status epilepticus. She was found to have superior sagittal sinus and right internal jugular vein thrombosis and protein S deficiency. CONCLUSION: The combination of protein S deficiency and the further reduction due to pregnancy may enhance the risk of major thrombotic episodes in the peripartum period.

DeLee suction. Does it have clinical significance?

OBJECTIVE: To evaluate the null hypothesis that there would be no difference in neonatal outcome in infants who underwent DeLee suction vs. those who underwent bulb suction when thick meconium was present. This difference was defined as a one-day difference in length of stay, two-point difference in the five-minute Apgar score or significant difference in blood gases. STUDY DESIGN: A power calculation based on a one-day length of stay found that 115 patients would be needed in each arm. A cohort of 115 consecutive deliveries with the presence of thick meconium was reviewed during each time period when DeLee suction was utilized and then matched with deliveries that used bulb suction. RESULTS: Two hundred thirty charts were reviewed. Length of stay, one-minute Apgar score, five-minute Apgar score, blood gases, gestational age and incidence of amnioinfusion were compared. There was no significant difference in any variable. Meconium aspiration syndrome in the period studied remained stable at < 1%. CONCLUSION: There was no significant clinical change in neonatal outcome with the abandonment of nasopharyngeal DeLee suction on the perineum when meconium was present. We recommend the use of bulb suction as routine obstetric practice even in the presence of thick meconium.

Laparoscopy during pregnancy. A survey of laparoendoscopic surgeons.

OBJECTIVE: The purpose of this study was to survey the Society of Laparoendoscopic Surgeons (SLS) for their experience with laparoscopy during pregnancy and to develop a database on the safety and complications of laparoscopy in pregnancy. STUDY DESIGN: A survey questionnaire was mailed to 16,329 laparoscopic surgeons from the SLS mailing database. Seven questions were asked: number of laparoscopic procedures in pregnancy, type of operation, gestational age, intraoperative and postoperative complications, insufflation agent and insufflation pressure. Only surgeons who had performed laparoscopic procedures in pregnancy were asked to return surveys. RESULTS: One hundred ninety-two (1.2%) surveys were returned. Complete information was available on 413 laparoscopic cases. There were five intraoperative complications, including inadvertent placement of a Veress needle into a pregnant uterus. There were 10 postoperative complications. CONCLUSION: This is the first report to specifically address the safety and complications of laparoscopy in pregnancy. This study suggests that laparoscopy may be safe during pregnancy; however, it was limited by the biases of surveys and retrospective studies.

Decreased expression of phosphorylated placental heat shock protein 27 in human and ovine intrauterine growth restriction (IUGR).

INTRODUCTION: Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. HSP27 has been shown to be involved in the control of apoptosis. Our objective is to determine the expression of phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27 during gestation in an ovine hyperthermia induced model of IUGR. METHODS: Human placenta tissue samples were collected at term to quantify p-HSP27. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days gestational age (dGA) to determined phosphorylated and total HSP27 across the development of IUGR. RESULTS: Phosphorylated HSP27 was significantly reduced in human placenta IUGR compared to controls at term. HSP27 was increased throughout gestation during the development of IUGR in the sheep. P-HSP27 was increased in early gestation (55 dGA), and decreased near term (130 dGA). The near term decrease was localized to the trophoblast cells of the placenta. DISCUSSION AND CONCLUSION: We conclude that decreased p-HSP27 at term is present when placental apoptosis is increased during IUGR. This could be a factor leading to the decreased placental weight observed during IUGR.

Increased trophoblast expression of NFAT5/TonEBP in pre-eclamptic placentas and hyperosmolar-treated BeWo cells.

OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.

Uterine artery blood flow volume in pregnant women with an abnormal pulsatility index of the uterine arteries delivering normal or intrauterine growth restricted newborns.

The aim of this study was to assess and compare uterine artery (UtA) blood flow volume in pregnant patients with an abnormal uterine Doppler pulsatility index (PI) who delivered fetuses with an appropriate weight for gestational age (AGA) or with intrauterine growth restricted (IUGR). We prospectively recruited singleton pregnancies with abnormal uterine arteries P.I. between 18 and 38 weeks of gestation regardless of estimated fetal weight (EFW). Vessel diameter and blood flow velocity were measured along the UtA upstream to the vessel bifurcation in both the right and left UtAs. Uterine blood flow volumes measured in these pregnancies were compared to historical Control-pregnancies. Forty-three patients delivered at term a normal weight newborn (AGA-pregnancies). Thirty patients delivered growth restricted newborns at 32 weeks (i.r. 29-36w) with a median weight of 1160 gr (i.r. 1000-2065 gr) (IUGR-pregnancies). At mid-gestation (18 + 0 - 25 + 6 weeks + days of gestation) a significantly lower uterine blood flow volume per unit weight was observed between the two study groups and compared to controls: 142 ml/min/kg in IUGR-pregnancies, 217 ml/min/kg in AGA-pregnancies and 538 ml/min/kg in Control-pregnancies. These striking differences in blood flow volume were already present at mid-gestation, at a time when EFW was still normal. In late gestation (27 + 0 - 37 + 6 weeks + days of gestation), pregnancies with an abnormal uterine P.I. showed persistently low UtA flow (<50% of controls) even when corrected for fetal weight: 81 ml/min/kg in IUGR-pregnancies, 105 ml/min/kg in AGA-pregnancies, and 193 ml/min/kg in Control-pregnancies; p < 0.0001. Our findings are consistent with other recent studies regarding the association between reduced uterine blood flow volume and fetal growth restriction. However, the study brings new insight into the finding of abnormal uterine P.I. in normally grown fetuses typically dismissed as "falsely abnormal" or "false positive" findings. Our study suggests that blood flow volume measurement may serve as a new tool to assess this group of patients and possibly those with ischemic placental diseases that may provide some basis for therapeutic interventions.

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.

Intravenous penicillin for antenatal syphilotherapy.

A 21 year old woman (G(2) P(0101)) of 24 weeks gestation presented with syphilis of unknown duration. Sonography revealed fetal hydrops and placental thickening. Weekly intramuscular injections of 2.4 million U Bicillin for 3 weeks was initiated as recommended by the Centers for Disease Control. Repeat sonogram 1 week after starting treatment revealed increased ascites and a new pericardial effusion. Due to the worsening fetal condition, therapy was altered and the patient was admitted for IV penicillin. She received a continuous infusion of 18 million U penicillin G daily for 10 days. Serial sonograms showed improvement offetal ascites and pericardial effusion with 10 days of IV therapy, and complete resolution of hydrops was noted within 3 weeks. The fetus was born at term with no stigmata of congenital syphilis on newborn exam, and laboratory tests suggested adequate treatment in utero.