Cost-effectiveness of estimating gestational age by ultrasonography in Down syndrome screening.

OBJECTIVE: To quantify the financial benefits of using ultrasound estimation of gestational age in maternal serum screening for Down syndrome. METHODS: Maternal age-specific sensitivity and false-positive rates for Down syndrome were derived for the triple test (alpha-fetoprotein, hCG, and unconjugated estriol) using gestational age based on ultrasound dating and also time from the last menstrual period (LMP). These rates were entered into a formula to determine the societal financial net benefit of Down syndrome screening. The average per-case net benefits of ultrasound- and LMP-dated pregnancies were then compared. Average net benefits were also calculated separately with ultrasound versus LMP dating for triple tests referred to our laboratory, and the additional costs associated with any post-test ultrasound scans, repeat testing, or recalculations were estimated. RESULTS: The use of ultrasound dating resulted in higher detection rates for Down syndrome and lower false-positive rates, which translated into an average per-case savings to society of $33.54. For women referred to our program with LMP dating, there was an average reduction of $31.60 in net benefits, plus added costs of $14.39 attributable to extra ultrasound, repeat testing, and recalculation. CONCLUSION: When ultrasound dating is available before serum screening, it should be used preferentially to establish Down syndrome risk. Routine first-trimester ultrasound examination can be justified for women with a known LMP if the cost of the ultrasound examination is less than $46.

Elevated maternal serum alpha-fetoprotein and mild fetal uropathy.

Sixty-one consecutive patients referred because of elevated maternal serum alpha-fetoprotein (MSAFP) levels and 80 referred for second-trimester ultrasound for other reasons were examined. Ultrasound examination of the genitourinary tract and assignment of phenotypic sex was done by ultrasonographers blinded to the MSAFP results. Among male fetuses with elevated MSAFP, 33% had pyelectasis compared with only 5% of controls. Among female fetuses, pyelectasis was seen in 16% of cases and no controls. Increased MSAFP not caused by an open neural tube defect may be seen in conjunction with mild benign uropathy in the second trimester.

Vanishing gastroschisis and short-bowel syndrome.

BACKGROUND: Gastroschisis occurs in 1 of every 4000 live births resulting in a neonate with an abdominal wall defect that requires repair. Surgical correction has high survival rates. CASE: An 18-year-old primigravida had a fetus with gastroschisis detected by ultrasound performed for elevated maternal serum alpha-fetoprotein. Subsequent ultrasound found resolution of the classic sonographic features of gastroschisis and evidence of intestinal obstruction. At birth, no obvious abdominal wall defect was seen. Laparotomy was done because of clinical and radiographic evidence of bowel obstruction, and we found significant bowel loss that resulted in short-bowel syndrome. CONCLUSION: Gastroschisis diagnosed antenatally can resolve in utero causing necrosis of portions of the small and large bowels, causing short-bowel syndrome and increased morbidity and mortality.

Iatrogenic monoamniotic twins as a complication of therapeutic amniocentesis.

BACKGROUND: Therapeutic amniocentesis has been accepted widely as a safe and efficacious way to treat the polyhydramnios-oligohydramnios sequence associated with twin-twin transfusion syndrome. CASE: A 28-year-old woman, gravida 2, para 1, diagnosed with twin-twin transfusion syndrome at 28 weeks' gestation was treated with serial amniocenteses. The dividing membrane was ruptured inadvertently during therapeutic amniocentesis, with subsequent complete disruption of the amniotic membrane. Iatrogenic monoamniotic twins with cord entanglement and knotting resulted. CONCLUSION: Creation of monoamniotic twins by disruption of the dividing membrane can be a complication of therapeutic amniocentesis for twin-twin transfusion syndrome. Such disruption may result in the same morbidity and mortality that are seen in naturally occurring monoamniotic twins.

Maternal smoking and accelerated placental maturation.

In a prospective study of 367 patients referred for obstetric ultrasound evaluation, maternal cigarette smoking was found to have an important effect on the rate of placental maturation. The frequencies of grades 0, I, II, and III placentas throughout gestation were determined for both smoking and nonsmoking groups. Overall, the smoking mothers had more mature placentas than the nonsmoking mothers. This was reflected by the earlier mean gestational age at appearance of each of the placental grades in the smoking group as compared with the nonsmoking group. The mean gestational ages at appearance of grades 0, I, II, and III placentas for smoking mothers were 23.5, 27.9, 32, and 34.4 weeks, respectively, as compared with 26, 31.6, 35.7, and 38.3 weeks in the nonsmoking group. Smokers had a greater frequency of grade II placentas from 22-35 weeks than nonsmokers, and a greater frequency of grade III placentas beyond 25 weeks.

Human parvovirus infection in pregnancy.

During an outbreak of fifth disease in the Hartford, Connecticut area in the winter of 1986, nine pregnant women were exposed to the parvovirus. Five of these nine had serologic evidence of previous exposure and immunity; all five had uneventful pregnancies. Three of the four women who exhibited serologic evidence of recent exposure to the parvovirus had hydropic fetuses who died, one of whom was anencephalic. Histologic and DNA hybridization studies suggest parvovirus infection as a cause for nonimmune hydrops and fetal death. A review of the literature suggests that of 37 women who were exposed and infected by human B19 parvovirus during pregnancy, 14 (38%) had adverse outcomes, including spontaneous abortions, intrauterine fetal death, and congenital anomalies. Women at high risk for exposure (school teachers) should have screening for immunoglobulin G parvovirus-specific antibodies; if these are absent, they should avoid close contact with schoolchildren. Pregnant women with evidence of recent infection should have a level II ultrasound. Because no vaccine is currently available, routine screening cannot be recommended.

A comparison of pre-discharge survival and morbidity in singleton and twin very low birth weight infants.

The perinatal mortality rate of twins is four to 11 times higher than that of singletons, and twins are widely reported to have more morbidity than singletons, mainly because of a higher preterm birth rate. However, it is not clear that live-born preterm birth rate. However, it is not clear that live-born preterm twins suffer greater morbidity than comparable singletons. In fact, twins have been reported to develop pulmonary maturity earlier than singletons, which might result in decreased morbidity relative to comparable preterm singletons. We conducted this retrospective review of 496 consecutive singleton and 104 twin infants weighing 500-1499 g and born alive at 24-31 weeks' gestation to determine whether pre-discharge survival and morbidity in very low birth weight (VLBW) twin infants were greater than those of comparable singletons. The mean (+/- standard deviation) gestational age of the singletons was 27.5 +/- 2.0 weeks and of the twins 27.6 +/- 2.0 weeks. There were no differences in mean gestational age, gestational age distribution, mean birth weight, birth weight distribution, gender, or maternal race between the two groups. The pre-discharge survival rate for twins (77%) was not significantly different than that of singletons (82%). There were no differences between twins and singletons in the incidences of neonatal respiratory distress syndrome (63 versus 71%), pulmonary interstitial emphysema (14 versus 16%), patent ductus arteriosus (28 versus 29%), necrotizing enterocolitis (3 versus 5%), intraventricular hemorrhage (11 versus 16%), and retinopathy of prematurity (11 versus 18%). The incidence of bronchopulmonary dysplasia was significantly less in twins (27 versus 46%; P = .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein.

OBJECTIVE: To evaluate the clinical significance of a second-trimester elevated maternal serum hCG in women carrying singleton, chromosomally normal fetuses. METHODS: The results of second-trimester maternal serum screening (alpha-fetoprotein [MSAFP], hCG, and unconjugated estriol) for 25,438 women were reviewed, and those with hCG values exceeding 3.0 multiples of the median (MoM) were identified. A control population was selected only on the basis of samples accessioned by the laboratory at the same time as the study group. Follow-up information was collected from physicians' offices for both groups. Incidence of fetal or neonatal loss (spontaneous abortion, fetal death, and neonatal death combined), preterm birth (before 37 weeks' gestation), small for gestational age, and preeclampsia were compared. RESULTS: Three hundred twenty-two women (1.3%) had hCG levels exceeding 3.0 MoM. In addition to chromosomal abnormalities and fetal death at the time of testing, this group showed a significantly higher incidence of fetal or neonatal death, preterm birth, low birth weight, and preeclampsia than did controls. For patients with elevated second-trimester hCG, many of the preterm deliveries occurred before 34 weeks' gestation. Logistic regression analysis indicated that hCG, MSAFP, and race were significant independent factors in predicting risk for adverse outcome. CONCLUSIONS: Similar to elevated AFP, elevated hCG is associated with poor pregnancy outcome. By combining the results of the two tests, it may be possible to improve substantially the identification of patients at very high risk for adverse outcomes.

Non-oral pyogenic granuloma in pregnancy: a report of two cases.

BACKGROUND: Pyogenic granulomas are benign vascular lesions of the skin or mucous membranes. Oral lesions are believed to occur in up to 2% of pregnancies. To the best of our knowledge, non-oral lesions in pregnancy have not been reported in the obstetric literature. CASES: We report two cases of non-oral pyogenic granuloma in pregnancy. The first, involving a finger lesion in a woman with triplets, demonstrated rapid growth and recurred after surgical excision. The second was an inguinal crease lesion, which was excised successfully after becoming symptomatic. CONCLUSION: Clinical experience suggests that the prevalence of pyogenic granulomas in pregnancy is not as high as has been reported in the literature. The relation of non-oral lesions to pregnancy is unknown.

Angiographic embolization of a ruptured renal artery aneurysm during pregnancy.

BACKGROUND: Ruptured arterial aneurysms during pregnancy usually are catastrophic, and the primary approach is surgical. Angiographic embolization is an alternative treatment. CASE: A 28-year-old primigravida with a history of congenital hepatic fibrosis presented at 23 weeks' gestation with abdominal pain, hypertension, and proteinuria. She underwent a cesarean delivery for preeclampsia and a retroperitoneal hematoma was noted. A postoperative angiogram revealed bilateral renal artery and splenic aneurysms. She underwent two angiographic embolizations of a ruptured right renal artery aneurysm and was discharged to undergo outpatient embolotherapy of the left renal and splenic aneurysms. The day after discharge, she died because of rupture of the splenic aneurysm. CONCLUSION: Aggressive management of ruptured and high-risk unruptured aneurysms during pregnancy is indicated. Embolotherapy is an alternate approach if surgery is not possible.

Long-term outcome of children following maternal human parvovirus B19 infection.

OBJECTIVE: To determine the long-term outcomes of children exposed in utero to maternal parvovirus B19 infection. METHODS: All pregnant women with serologic evidence of recent parvovirus B19 infection and a comparison group with serologic evidence of past infection from January 1988 to December 1994 were sent questionnaires or contacted by phone about the health and development of their children. Information requested included: pregnancy complications, date of delivery, birth weight, sex, birth defects, need for special care, significant health problems, and developmental delays. All women had serology done at either the Centers for Disease Control and Prevention or the virology laboratory of the Connecticut Department of Health. The data were analyzed using descriptive statistics, chi2 analysis with Fisher exact test, or Student t test in appropriate cases. P < .05 was considered significant. RESULTS: Outcome information was obtained from 113 of 117 immunoglobulin-M positive women. The 113 respondents had 103 term singletons, two sets of twins (of which one neonate died of complications of prematurity), one hydropic stillborn, four spontaneous abortions, and one ectopic pregnancy. The mean gestational age at time of exposure was 15.6 weeks. The median age of the liveborn infants in study and comparison groups was 4 years. Eight of the 108 (7.3%) surviving children, one set of twins (exposed at 27 weeks), and six singletons (exposed at 7, 8, 9, 20, 27, and 35 weeks) had developmental delays in speech, language, information processing, and attention. Outcomes were obtained for 99 of 110 patients with past infection; they had 83 liveborn singletons, five sets of twins, two stillborns, and five spontaneous abortions. Seven of the 93 (7.5%) children had developmental delays, similar to the study group. Post-hoc power analysis revealed that 712 infected patients would be needed to find a twofold difference in the risk of abnormal neurologic development; our study had 30% power to find such a difference. CONCLUSION: There is no apparent increase in the frequency of developmental delays in children with exposure in utero to parvovirus, but larger studies are needed.

Calculated risk of chromosomal abnormalities in twin gestations.

Genetic counseling concerning the risks of chromosomal abnormalities in twin gestations can be difficult; the risk of amniocentesis is weighed against that of chromosomal abnormalities in either one or both of the twins. Because most twins are dizygotic (each with a risk a priori of aneuploidy), the chance that one of the fetuses is affected is greater than would be expected for a singleton. Only three possibilities would result in either one or both twin's being affected: 1) dizygotic twins with one fetus affected, 2) dizygotic twins with both fetuses affected, and 3) monozygotic twins with both fetuses affected. Using existing tables of estimated risks of chromosomal abnormalities in singleton gestations and mathematically derived formulas, we created tables defining the age-related risks of chromosomal abnormalities in twin gestations. According to these tables, a patient at 33 years of age with a twin gestation has a risk of Down syndrome in at least one of her twins equivalent to that of a 35-year-old with a singleton. Prenatal genetic testing should be considered for women with twins at a younger age than the traditional 35.

Spontaneous resolution of fetal cystic hygroma in Down's syndrome.

We describe a case of spontaneous resolution of a cystic hygroma between 14-16 weeks' gestation in a fetus with trisomy 21 who, at termination at 19 weeks, revealed only mild webbing of the neck. Redundant nuchal skin folds are among the most common features of trisomy 21. Our case supports the hypothesis that this redundant skin of the fetal neck represents early cystic hygromas, which resolve in utero before 16 weeks' gestation.

Pregnancy outcome following first-trimester varicella infection.

Varicella infection in the first trimester has been associated with a constellation of congenital abnormalities. The incidence of the congenital varicella syndrome is unknown, although it has been reported to be as high as 9%. In a prospective study performed between 1986-1990, 40 patients were identified who had first-trimester varicella infection. Pregnant patients were referred from physicians in the perinatal regional network after developing the classical picture of varicella infection. Targeted fetal ultrasound examinations were performed between 16-20 weeks' gestation in all cases and neonatal outcome was determined. Of the 40 patients, three had first-trimester losses and another underwent an elective termination of pregnancy after counseling. Of the remaining 36 women, one had fetal omphalocele. Thirty-five pregnancies continued until term, and no infant had features of the congenital varicella syndrome at birth. Other than the case of omphalocele, no major congenital anomalies were identified. This study, the largest series of patients with first-trimester varicella infection, showed an incidence of congenital varicella syndrome of 0% and an incidence of congenital anomalies of 3% (range 0-8% at 95% confidence level).

Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial.

OBJECTIVE: To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects. METHODS: Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis. RESULTS: The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills. CONCLUSION: Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.

Atypical presentation of preeclampsia in high-order multifetal gestations.

OBJECTIVE: To describe our experience with preeclampsia in high-order multifetal gestations. METHODS: Records for all triplet and quadruplet pregnancies delivered after 24 weeks' gestation from January 1988 through June 1994 were reviewed. All patients were treated with bed rest from 20 weeks' gestation onward and received corticosteroids weekly beginning at 24 weeks. Tocolytics were used as needed. RESULTS: Twenty-one triplet and eight quadruplet pregnancies were studied. The mean gestational age at delivery was 32.3 and 27.9 weeks, and mean birth weights were 1547 and 1028 g, respectively. Seventeen of 29 patients developed preeclampsia, 14 of the 21 triplet mothers and three of the eight quadruplet mothers. Among 16 patients who were delivered for preeclampsia, only eight had blood pressure (BP) elevation before delivery, whereas ten had epigastric pain, visual disturbances and/or headache; nine had elevated liver enzyme levels; and seven had low platelet counts. Only three patients had proteinuria, and only six had edema. Five women developed the syndrome of hemolysis, elevated liver enzymes, and low platelets postpartum, all of whom had normal BP before delivery. Two patients developed preeclampsia after delivery. A total of 95 infants were delivered, all by cesarean, of whom 93 (98%) survived. CONCLUSION: Preeclampsia is common in high-order multifetal gestations and often presents in an atypical manner. Hypertension is not always the presenting sign, and symptoms consistent with severe preeclampsia and abnormal laboratory values predominate.

Ear length in second-trimester aneuploid fetuses.

OBJECTIVE: To test the hypothesis that small ears have diagnostic value in detecting second-trimester aneuploid fetuses by ultrasound. METHODS: We prospectively studied 452 patients with singleton pregnancies undergoing ultrasound examination for genetic amniocentesis at 14-25 weeks and an additional 30 singleton pregnancies at 20-25 weeks with a negative anomaly screen. Standard fetal biometry measurements were obtained, including ear length (from helix to end of lobe). RESULTS: Of these patients, 424 (88%) had ear measurements obtained, and a nomogram for ear length by gestational age was compiled. The relationship between ear length and gestational age was linear across the second trimester (r = 0.84, P < .001). Fourteen fetuses had aneuploidy by amniocentesis, of whom ten had ear lengths at or below the tenth percentile. The sensitivity was 71% and the specificity 92% (377 of 410). Positive and negative predictive values were 23% (ten of 43) and 99% (377 of 381), respectively. CONCLUSION: Fetal ear length may be useful in identifying aneuploid fetuses sonographically during the second trimester.

Maternal serum screening for fetal trisomy 18: a comparison of fixed cutoff and patient-specific risk protocols.

OBJECTIVE: To compare the effectiveness of two widely used protocols for second-trimester screening for fetal trisomy 18. METHODS: Second-trimester screening results for 41,565 women were reviewed to determine whether pregnancies could be considered to be at high risk for trisomy 18. The screening test was considered positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3) fell below defined levels, or the second-trimester patient-specific risk (based on maternal age and serum analytes) was greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes for the two protocols were compared. RESULTS: The fixed-cutoff method showed a 23% detection rate and a 0.19% false-positive rate for trisomy 18. These low rates were in close agreement with a theoretical expectation for fixed-cutoff trisomy 18 screening. The risk-based approach resulted in a 69% detection rate and a 0.45% false-positive rate. Both methods identified pregnancies with other fetal anomalies. CONCLUSION: Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.

Placenta previa is not an independent risk factor for a small for gestational age infant.

Previous studies have presented conflicting evidence on the association between intrauterine growth retardation (IUGR) and placenta previa, with some groups reporting rates of IUGR as high as 16-19%. However, most of these studies failed to include a control population, included patients with other factors known to be associated with IUGR (eg, chronic hypertension, fetal anomalies, pregnancy-induced hypertension, insulin-dependent diabetes mellitus, etc), and/or did not confirm the patient's estimated gestational age. During the study period of January 1, 1980 through June 30, 1990, 54,969 deliveries occurred at the three affiliated hospitals of the Maternal-Fetal Medicine Division of the University of Connecticut Health Center. Review of the delivery records revealed 179 singleton pregnancies with documented placenta previa and without the above exclusion factors. One hundred seventy-one of these 179 study patients were compared with 171 women without placenta previa matched for confirmed gestational age, race, parity, and fetal sex. The incidence of small for gestational age (SGA) infants was 4.1% (seven of 171) in the study group and 5.8% (ten of 171) in the control group. Mean birth weights were 2559 and 2476 g, respectively. Neither difference was statistically significant. These results suggest that the prenatal diagnosis of an SGA fetus in a pregnancy complicated by placenta previa should not simply be attributed to abnormal placental implantation. Furthermore, routine ultrasonic examinations for growth in pregnancies complicated by placenta previa are not indicated.

Transverse cerebellar diameter/abdominal circumference ratio throughout pregnancy: a gestational age-independent method to assess fetal growth.

In a prospective study of 162 patients, measurements of the transverse cerebellar diameter (TCD) and abdominal circumference (AC) were obtained between 15-38 weeks' gestation. A ratio between the TCD and AC was calculated after each examination. This ratio remained constant during gestation. The mean ratio was 13.7% (fifth and 95th percentiles of 11.9 and 15.9%, respectively); the median ratio was 13.6%. Forty-two patients had repeat measurements and the ratio did not change. This ratio is gestational age-independent; however, further investigation is needed to determine its application in the assessment of fetal growth abnormalities.