Prenatal diagnosis of retinal detachment in Walker-Warburg syndrome.

Lissencephaly, hydrocephalus, and eye abnormalities characterize patients with the Walker-Warburg syndrome, an uncommon autosomal recessive condition. Encephaloceles occur in about 50% of patients. We describe the prenatal diagnosis of this condition based on the ultrasonographic findings of retinal detachment, hydrocephalus, and an encephalocele in a fetus not known to be at risk.

Prenatal diagnosis of gastroschisis: development of objective sonographic criteria for predicting outcome.

OBJECTIVE: To determine which sonographic findings predict intestinal damage in fetuses with gastroschisis, and to develop objective criteria that may be useful in selecting candidates for preterm delivery. METHODS: Twenty-four consecutive fetuses at two perinatal centers were assessed retrospectively or prospectively. Maternal, perinatal, and sonographic data were recorded and correlated with postnatal outcome. RESULTS: Bowel diameter of at least 18 mm was associated with a significantly longer time to oral feeding and with significantly greater need for bowel resection. When gestational age was plotted against bowel diameter, a threshold curve was generated, above which all patients had prolonged hypoperistalsis and below which only 30% had prolonged hypoperistalsis. Two infants were delivered at 33 weeks' gestation, both of whom had complications potentially related to prematurity. Only one of 22 patients who delivered later than 33 weeks had similar complications. CONCLUSIONS: Bowel dilatation may be a marker of prenatal bowel damage in fetuses with gastroschisis, especially when it presents late in gestation. Prenatal sonography may be useful in selecting appropriate fetuses for preterm delivery.

False diagnosis of intestinal obstruction in a fetus with congenital chloride diarrhea.

Intestinal obstruction is often diagnosed prenatally by ultrasound, providing an opportunity for prenatal counseling, genetic investigation, and planned delivery at a perinatal center. We describe a patient with typical features of fetal bowel obstruction, who was found at birth to have congenital chloride diarrhea. A 25-year-old white woman had marked polyhydramnios; multiple dilated, fluid-filled loops of intestine were seen in the fetal abdomen on prenatal ultrasound. However, postnatally, there was no evidence of bowel obstruction. The infant girl passed large amounts of watery stools, but tolerated feeds well. A rectal biopsy showed normal ganglion cells. On the fourth day of life her serum sodium and chloride were markedly decreased, and stool chloride levels were diagnostic of congenital chloride diarrhea. She was placed on sodium chloride and potassium chloride supplements, and her serum electrolytes normalized. Congenital chloride diarrhea is a rare, inherited condition caused by an abnormality of intestinal electrolyte transport. This case illustrates that it may present prenatally with a picture similar to that seen with intestinal obstruction.

Cloacal exstrophy: prenatal diagnosis before rupture of the cloacal membrane.

Embryologically, cloacal exstrophy is thought to result from persistence and subsequent rupture of the infraumbilical cloacal membrane during the fifth embryonic week. We report a case of cloacal exstrophy in which a prenatal diagnosis was made prior to rupture of the cloacal membrane. A routine ultrasound at 17 weeks' gestation demonstrated monoamniotic twins. One twin was normal, but the other was found to have a sacral myelomeningocele, "rocker-bottom" feet, splaying of the pubic rami, and a large cystic mass protruding from the infraumbilical anterior abdominal wall. A repeat ultrasound was performed at 22 weeks, with the same findings. At 26 weeks, further examination showed disappearance of the abdominal cyst, a small omphalocele, no demonstrable bladder, and the suggestion of prolapsed bowel inferior to the umbilical cord insertion. After delivery at 34 weeks, the abnormal twin was found to have the typical findings of cloacal exstrophy, myelomeningocele, bilateral lower limb anomalies, and extremely foreshortened small bowel. Rupture of the presumed cloacal membrane after 22 weeks in this case is inconsistent with our current understanding of the embryology of this anomaly, and should stimulate a reexamination of the current concepts. If the characteristic features are recognized, cloacal exstrophy can be diagnosed by prenatal ultrasound, permitting prenatal counseling and appropriate perinatal management.

Neonatal alloimmune thrombocytopenia: spontaneous in utero intracranial hemorrhage.

Neonatal alloimmune thrombocytopenia is an uncommon but important cause of thrombocytopenia in infants. Because of the severity of the thrombocytopenia, some of these infants will have intracranial hemorrhage with resultant long-term disability. Obstetricians and neonatologists have recommended delivery by caesarean section and the rapid institution of appropriate treatment for the infant; however, it is theoretically possible that a hemorrhagic event could precede the delivery and consequently not be prevented by these perinatal interventions. In this report we describe a neonate in whom the diagnosis of alloimmune neonatal thrombocytopenia was suspected because of antenatal ultrasound evidence of intracerebral hemorrhage. This case demonstrates the importance of antenatal fetal assessment and indicates the need for the development of therapeutic strategies to maintain fetal hemostasis.

Transvaginal ultrasound scanning in early pregnancy and correlation with human chorionic gonadotropin levels.

Pregnancy can be detected early using transvaginal ultrasonography and human chorionic gonadotropin (hCG) measurements. The purpose of this study was to correlate serum hCG levels with transvaginal gestational sac measurements. The mean sac diameter (MSD) and gestational sac diameter (GSD) were calculated as the mean and cube root of the product, respectively, of three sac dimensions taken at right angles. A nonlinear relationship between hCG (natural logarithm) and MSD and GSD was observed. The data were best fitted by a second order polynomial regression model (r2 = 0.98), thereby establishing normal hCG levels for various gestational sac dimensions in early pregnancy.

Early pregnancy assessment with transvaginal ultrasound scanning.

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen.

Multiple cardiac masses diagnosed with prenatal ultrasonography in the fetus of a woman with tuberous sclerosis.

Cardiac rhabdomyomas are associated with tuberous sclerosis, but their identification in utero is uncommon. The authors report a case of multiple cardiac masses discovered in utero by prenatal ultrasonography at about 30 weeks gestational age. Follow-up included neonatal echocardiography, ultrasonography and computed tomography of the head. The differential diagnosis of echogenic intracardiac masses, as well as their management, is discussed.

Do sick newborn infants benefit from participation in a randomized clinical trial?

BACKGROUND: Adult participants in randomized controlled trials often have better outcomes than patients who are eligible but not enrolled. OBJECTIVE: To examine whether newborn infants who were allocated to placebo in an investigational drug trial had better outcomes than infants who were eligible but not randomized (eligible NR). STUDY DESIGN: During a randomized controlled trial of antithrombin therapy in premature infants with respiratory distress syndrome, data were collected prospectively on all 76 infants in the eligible NR group. Study outcomes were compared with those of all 61 infants who were randomized to placebo. The same exogenous surfactant was used in all patients. RESULTS: In the placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group, mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2. 3) weeks, and 58% were male; 57% of infants in both groups had been exposed to steroids before birth. The median duration of mechanical ventilation was reduced from 6.2 days in the eligible NR group to 4. 8 days in the placebo group (P =.008). There was also a trend toward less frequent and less severe intraventricular hemorrhage in trial participants. CONCLUSIONS: These data are consistent with the hypothesis that sick newborn infants may benefit from participation in a randomized controlled trial.

A placebo-controlled randomized trial of antithrombin therapy in neonatal respiratory distress syndrome.

Neonatal respiratory distress syndrome (RDS) is associated with decreased plasma activity of antithrombin (AT) and increased formation of thrombin. We tested whether AT reduces thrombin formation, improves gas exchange, and decreases the duration of mechanical ventilation and supplemental oxygen. One hundred twenty-two infants were randomized to pasteurized AT concentrate or to placebo. Two ml/kg (equivalent to 100 IU AT/kg) were followed by 1 ml/kg (50 IU/kg) every 6 h for 48 h. Outcome measures included plasma AT activity, thrombin-AT (TAT) complex, prothrombin fragment (F1+2), the ratio of arterial to alveolar oxygen pressure [(a/A)PO2], and the ventilator efficiency index (VEI). In the AT group (n = 61), mean (SD) birth weight was 1,198 (301) g, mean (SD) gestational age (GA) was 28.3 (2.0) wk, 54% were male. In the placebo group (n = 61), mean (SD) birth weight was 1,201 (315) g, mean (SD) GA was 28.8 (2. 3) wk, 51% were male. In treated infants, AT activity was raised to means of 1.69 and 2.25 U/ml at 24 and 48 h, respectively. Corresponding means in control infants were 0.37 and 0.44 U/ml (p < 0.0001). F1+2, but not TAT, was significantly reduced by AT (p = 0. 004). VEI and (a/A)PO2 were similar in both groups throughout the first week of life. Median days receiving mechanical ventilation were 7.1 (AT) versus 4.8 (placebo), p = 0.0014. Median days receiving supplemental oxygen were 7.9 (AT) versus 5.5 (placebo), p < 0.0001. There were seven (11.5%) deaths in the AT group and three (4.9%) deaths in the placebo group. We conclude that treatment with AT cannot be recommended in premature infants with RDS.

Neonatal outcome of fetuses with urinary tract abnormalities diagnosed by prenatal ultrasonography.

Between 1979 and 1986 an abnormality of the urinary tract was diagnosed by prenatal ultrasound examination in 93 fetuses. Postnatal investigation at a large teaching hospital showed a definite abnormality in 85 infants, 66 of whom were boys. An obstructed urinary tract, usually requiring surgery, was present in 46 infants. Other abnormalities included a multicystic kidney (in 15 infants), vesicoureteric reflux (in 9), prune-belly syndrome (in 5) and polycystic kidneys (in 5). Early recognition and treatment of urinary tract disorders in infants should be accompanied by informed prenatal counselling to minimize parents' anxiety.

Thrombin/antithrombin III complex formation in the neonatal respiratory distress syndrome.

Intravascular and intra-alveolar thrombin generation may exacerbate the pulmonary hypertension and surfactant dysfunction that characterize the neonatal respiratory distress syndrome (RDS). Although low levels of the most important thrombin inhibitor, antithrombin III (AT III), have been reported in infants with RDS, direct evidence of increased intravascular thrombin generation has been lacking. Accordingly, the objective of this study was to determine whether thrombin generation is increased in severe neonatal RDS. Thirty-nine infants of 25 to 29 wk gestation with a clinical and radiologic diagnosis of RDS were enrolled in a prospective cohort study. Plasma levels of thrombin/antithrombin III complexes (TAT) and AT III activity, measured 36 to 72 h after birth, were related to RDS severity. Seventeen infants had severe RDS (mean airway pressure greater than 10 cm H2O or FlO2 greater than 0.8), and 22 had mild or moderate disease. Mean birthweight (1,017 versus 1,054 g) and mean gestational age (27.8 versus 27.4 wk) were similar in both groups. The median TAT level in infants with severe RDS was significantly higher than that in patients with mild or moderate disease (10.7 and 4.0 micrograms/L, respectively; p less than 0.001). In addition, the mean AT III activity in infants with severe RDS was significantly lower than that in less severely affected patients (0.31 and 0.46 U/ml, respectively; p less than 0.01). Considering the entire cohort, plasma TAT levels were inversely correlated with the arterial/alveolar oxygen tension ratio (r = -0.48, p = 0.0022) and the ventilator efficiency index (r = -0.51, p = 0.0011). The elevated TAT levels and reduced AT III activity in infants with severe RDS are consistent with increased thrombin generation and resulting AT III consumption. Therefore, to regulate thrombin activity, these infants may benefit from replacement therapy with AT III concentrate.

Management of prenatally diagnosed tracheal obstruction: access to the airway in utero prior to delivery.

A fetus of 23-weeks gestation presented with polyhydramnios, and was found on sonography to have a large anterior cervical teratoma. At 26 weeks the mother went into premature labor and the membranes ruptured; at this time the uterus was of 32-weeks size secondary to polyhydramnios. A cesarean section was performed through a low transverse uterine incision, and the fetal head and shoulders were delivered with the cord intact. An endotracheal tube was placed, and the cord was then divided. The baby was taken to the neonatal intensive care unit for stabilization prior to planned resection, but suffered pharyngeal hemorrhage followed by endotracheal tube dislodgement several hours after birth, and expired. Despite an unfortunate outcome, this case illustrates the feasibility and potential value of in utero airway access in cases of prenatally diagnosed tracheal obstruction.

A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.

A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Venous thrombosis in patients who have undergone major hip or knee surgery: detection with compression US and impedance plethysmography.

To compare the sensitivity, specificity, and predictive values of compression ultrasonography (US) in postoperative orthopedic patients with those of (a) impedance plethysmography in postoperative patients and (b) compression US in symptomatic outpatients, the authors performed an investigator-blinded cohort study. One hundred thirty-four consecutive inpatients who had undergone elective knee-replacement surgery or surgery for a fractured hip and 65 consecutive outpatients with clinically suspected venous thrombosis who had undergone venography were evaluated. Compression US allowed detection of 11 of 21 (52.4%) proximal-vein thrombi but was insensitive to calf-vein thrombi in the orthopedic patients. Compression US had a significantly greater specificity and positive predictive value than impedance plethysmography for all thrombi in orthopedic patients; compression US also had greater sensitivity. The sensitivity of compression US for proximal-vein thrombi was significantly higher (92.1%) in symptomatic outpatients than in orthopedic patients. The authors conclude that compression US has significant advantages over impedance plethysmography in the detection of proximal-vein thrombi in patients who have undergone hip- or knee-replacement surgery.