Robert Resnik

Intrauterine Growth Restriction

Fetal intrauterine growth restriction presents a complex management problem for the clinician. The failure of a fetus to achieve its growth potential imparts a significantly increased risk of perinatal morbidity and mortality. Consequently, the obstetrician must recognize and accurately diagnose inadequate fetal growth and attempt to determine its cause. Growth aberrations, which are the result of intrinsic fetal factors such as aneuploidy and multifactorial congenital malformations, and fetal infection, carry a guarded prognosis. However, when intrauterine growth restriction is caused by placental abnormalities or maternal disease, the growth aberration is usually the consequence of inadequate substrates for fetal metabolism and, to a greater or lesser degree, decreased oxygen availability. Careful monitoring of fetal growth and well-being, combined with appropriate timing and mode of delivery, can best ensure a favorable outcome. Ultrasound evaluation of fetal growth, behavior, and measurement of impedance to blood flow in fetal arterial and venous vessels form the cornerstone of evaluation of fetal condition and decision making.

Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of placenta accreta

BACKGROUND: The incidence of placenta accreta has increased dramatically over the last three decades, in concert with the increase in the cesarean delivery rate. Optimal management requires accurate prenatal diagnosis. The purpose of this study was to determine the precision and reliability of ultrasonography and magnetic resonance imaging (MRI) in diagnosing placenta accreta. METHODS: A historical cohort study was performed with information gathered from our obstetric, radiologic, and pathology databases. Records from January 2000 to June 2005 were reviewed to identify patients with a diagnosis of placenta previa, low-lying placenta with a prior cesarean delivery, or history of a myomectomy to determine the accuracy of pelvic ultrasonography in the diagnosis of placenta accreta. The records of those considered to be suspicious for placenta accreta and subsequently referred for additional confirmation by MRI were also analyzed. The sonographic and MRI diagnoses were compared with the final pathologic or operative findings or with both. RESULTS: Of the 453 women with placenta previa, previous cesarean delivery and low-lying anterior placenta, or previous myomectomy, 39 had placenta accreta confirmed by pathological examination. Ultrasonography accurately predicted placenta accreta in 30 of 39 of women and correctly ruled out placenta accreta in 398 of 414 without placenta accreta (sensitivity 0.77, specificity 0.96). Forty-two women underwent MRI evaluation because of findings suspicious or inconclusive of placenta accreta by ultrasonography. Magnetic resonance imaging accurately predicted placenta accreta in 23 of 26 cases with placenta accreta and correctly ruled out placenta accreta in 14 of 14 (sensitivity 0.88, specificity 1.0). CONCLUSION: A two-stage protocol for evaluating women at high risk for placenta accreta, which uses ultrasonography first, and then MRI for cases with inconclusive ultrasound features, will optimize diagnostic accuracy. LEVEL OF EVIDENCE: II-3

Antenatal origin of neurologic damage in newborn infants. I. Preterm infants.

Currently, the diagnosis of white matter necrosis may be performed with echoencephalography when cysts are observed in the white matter adjacent to the lateral ventricles. One hundred twenty-seven infants with a gestational age

Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus

Cocaine is a potent vasoconstrictive agent that is currently the subject of widespread drug abuse. Because little is known of the physiologic responses to cocaine in pregnancy, the effects of intravenous cocaine on uterine blood flow and other maternal and fetal cardiovascular parameters were studied. Eight ewes in late pregnancy were equipped with electromagnetic flow probes around both uterine arteries and catheters were placed in the maternal and fetal inferior vena cavae and aortas. Bolus intravenous infusion of 0.5 and 1.0 mg/kg of maternal body weight achieved peak plasma cocaine levels similar to those observed in human subjects after abuse of the drug (mean level = 229 to 400 ng/ml, n = 8). After bolus infusion of 0.5 or 1.0 mg/kg of cocaine, mean maternal arterial pressure increased 32% and 37%, respectively (p less than 0.005). Fetal blood pressure rose 12.6% after a dosage of 0.5 mg/kg of cocaine. These cocaine infusions significantly decreased uterine blood flow by 36% and 42% for a duration of 15 minutes (p less than 0.005). Analysis of maternal catecholamine responses demonstrated a significant (210%) rise in plasma norepinephrine levels after cocaine infusion. These studies demonstrate that cocaine, when administered in doses that produce plasma levels observed in humans, significantly decreases uterine blood flow for a duration of greater than or equal to 15 minutes while inducing a hypertensive response in the pregnant ewe and fetus.

Effect of predelivery diagnosis in 99 consecutive cases of placenta accreta.

OBJECTIVE: To estimate the effects of prenatal diagnosis and delivery planning on outcomes in patients with placenta accreta. METHODS: A review was performed of all patients with pathologically confirmed placenta accreta at the University of California, San Diego Medical Center from January 1990 to April 2008. Cases were divided into those with and without predelivery diagnosis of placenta accreta. Patients with prenatal diagnosis of placenta accreta were scheduled for planned en bloc hysterectomy without removal of the placenta at 34–35 weeks of gestation after betamethasone administration. Maternal and neonatal outcomes were assessed. RESULTS: Ninety-nine women with placenta accreta were identified, of whom 62 were diagnosed before delivery and 37 were diagnosed intrapartum. Comparing women with predelivery diagnosis with those diagnosed at the time of delivery, there were fewer units of packed red blood cells transfused (4.7±2.2 compared with 6.9±1.8 units, P=.02) and a lower estimated blood loss (2,344±1.7 compared with 2,951±1.8 mL, P=.053), although this trend did not reach statistical significance. Comparison of neonatal outcomes demonstrated a higher rate of steroid administration (65% compared with 16%, P≤.001), neonatal admission to the neonatal intensive care unit (NICU) (86% compared with 60%, P=.005), and longer neonatal hospital stays (10.7±1.9 compared with 6.9±2.1 days, P=.006). Length of NICU stay, rates of respiratory distress syndrome, and surfactant administration did not differ between the groups. CONCLUSION: Predelivery diagnosis of placenta accreta is associated with decreased maternal hemorrhagic morbidity. Planned delivery at 34–35 weeks of gestation in this cohort did not significantly increase neonatal morbidity. LEVEL OF EVIDENCE: II

Antenatal origin of neurologic damage in newborn infantsII. Multiple gestations

Necrosis of the cerebral white matter may be identified in living infants with echoencephalography. Echoencephalographic studies were performed in 89 twins and 12 triplets at less than 36 weeks of gestation to determine the incidence and complications associated with antenatal necrosis of the cerebral white matter. Antenatal necrosis of the cerebral white matter was identified when brain atrophy or cavities in the white matter were present by day 3 of life. Fourteen infants (13.8%) were considered to have antenatal necrosis of the cerebral white matter. The incidence of antenatal necrosis of the cerebral white matter was higher in monochorionic than in dichorionic infants (30% vs 3.3%; p less than 0.001). Univariate analysis showed that antenatal necrosis of the cerebral white matter was significantly associated with polyhydramnios, intrauterine fetal death of the cotwin, hydrops, multiple placental vascular connections, and placental artery-to-artery, vein-to-vein, and artery-to-vein anastomosis. Logistic regression analysis showed that antenatal necrosis of the cerebral white matter was predicted by the presence of either artery-to-artery or vein-to-vein anastomosis and by intrauterine fetal death of a cotwin. Vein-to-vein anastomosis had the strongest association, because 89% of seven infants with vein-to-vein anastomosis demonstrated antenatal necrosis of the cerebral white matter (p = 0.003). Monochorionic multiple gestations frequently are complicated by antenatal necrosis of the cerebral white matter. Multiple vascular connections with vein-to-vein anastomosis appear as the most important associated factor for antenatal necrosis of the cerebral white matter in this population.

Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia

OBJECTIVE The antenatal and intrapartum management of women with autoimmune thrombocytopenia is controversial. The current approach emphasizes an effort to identify maternal characteristics predictive of severe neonatal thrombocytopenia or to measure fetal platelet counts and perform cesarean section in patients considered to be at risk for neonatal intracranial hemorrhage. In the current study we review our experience with maternal autoimmune thrombocytopenia and neonatal outcome. STUDY DESIGN Fifty-five pregnancies with autoimmune thrombocytopenia over a 10-year period in three major medical centers in San Diego, California, were evaluated. Maternal characteristics and neonatal outcomes were assessed and compared with those in other recent reports. Data were submitted to Fishers exact (two-tailed), chi2, and Student t tests, with linear regression performed to analyze the association between variables. RESULTS Maternal characteristics including platelet count, presence of antiplatelet antibody, antecedent history of autoimmune thrombocytopenia, and corticosteroid therapy were not predictive of severe neonatal thrombocytopenia. Maternal history of splenectomy was significantly correlated with fetal platelet counts <50 x 10(9)/L (odds ratio 5.63; 95% confidence interval 2.2 to 14.3). There were four neonates with severe neonatal thrombocytopenia (8%), and one who was delivered by cesarean section had intracranial hemorrhage. CONCLUSIONS These findings, combined with others in the literature, confirm that severe neonatal thrombocytopenia is an infrequent complication of maternal autoimmune thrombocytopenia and is not reliably predicted by maternal characteristics. Intracranial hemorrhage is also a rare event and is not related to mode of delivery. Cesarean section should be reserved for obstetric indications only.

The association of maternal floor infarction of the placenta with adverse perinatal outcome

Maternal floor infarction of the placenta is a relatively rare disorder that on gross examination is characterized by a thickened gray-yellow maternal floor of the placenta with histologic evidence of massive fibrin deposition involving the decidua basalis and the contiguous villi. This lesion has been associated with fetal death, preterm delivery, and intrauterine growth retardation and is thought to be recurrent. Sixty cases of maternal floor infarction were identified in 48 women. Fetal death occurred in 24 of the 60 cases (40%). Preterm birth occurred in 21 of 36 (58.3%) live-born infants, and 19 of the 35 (54.2%) live-born infants for whom a birth weight was known had evidence of intrauterine growth retardation. Among the 41 multiparous patients in our series there were five documented recurrences (12.2%). Review of the past reproductive history of these 48 patients (196 pregnancies) demonstrated a significant incidence of fetal death (24.1%), intrauterine growth retardation (31.3%), and preterm death (35.4%). The association of fetal death and maternal floor infarction emphasizes the importance of a placental examination with all cases of fetal death and infants with intrauterine growth retardation. Given the risk of recurrence, the identification of maternal floor infarction should alert the clinician to the potential for growth retardation, preterm birth, and fetal death in subsequent pregnancies.

Catecholamine-mediated reduction in uterine blood flow after nicotine infusion in the pregnant ewe.

The effect of nicotine on uterine blood flow, uterine vascular resistance, and plasma catecholamine concentration was studied in chronically catheterized pregnant sheep equipped with electromagnetic flow probes. The systemic administration of nicotine (14--32 micrograms/kg body wt per min) resulted in a 44% reduction in uterine blood flow (P less than 0.001) and a 203% increase in uterine vascular resistance. Both responses were inhibited by pretreatment with the alpha blocker, phentolamine. Arterial plasma concentrations of norepinephrine and epinephrine, measured by a single isotopic radioenzymatic assay, rose (from 117.9 +/- 6.7 to 201.8 +/- 13.3 pg/ml, P less than 0.001; and from 71.6 +/- 4.5 to 124.1 +/- 8.4 pg/ml, P less than 0.001, respectively) during nicotine infusion. The findings suggest that nicotine exerts a deleterious effect on uterine blood flow mediated through the release of catecholamines.

The effect of progesterone on estrogen-induced uterine blood flow

The effect of progesterone on estrogen-induced uterine blood flow was investigated in repeated experiments in seven nonpregnant, oophorectomized ewes with chronically implanted electromagnetic flow probes and catheters inserted into branches of the uterine arteries. Administered alone, progesterone has no effect on base-line uterine blood flow. Following intramuscular injection of progesterone (3 to 5 mg-per kilogram of body weight), peak uterine blood flow responses to 1 microng of estradiol-17beta were suppressed by 25 per cent compared to those of control animals. Direct intra-arterial infusion of progesterone, at concentrations sufficient to reproduce uterine venous levels observed in late pregnancy in the sheep, inhibited estrogen-induced uterine blood flow by 20 per cent. The findings support the hypothesis that progesterone modulates the estrogen-induced flow responses in both the pregnant and nonpregnant uterine vascular bed.