Jeffrey M. Dicke

Revisiting the Fetal Loss Rate After Second-Trimester Genetic Amniocentesis : A Single Center's 16-Year Experience

OBJECTIVE: To estimate an institution’s specific fetal loss rate after a second-trimester genetic amniocentesis. METHODS: This is a retrospective cohort study using our prenatal diagnosis database for all pregnant women presenting for care between 1990 and 2006. We compared the fetal loss rate in women who underwent amniocentesis between 15 and 22 weeks of gestation with those women who did not have any invasive procedure and had a live fetus documented on ultrasound examination between 15 and 22 weeks. Only singleton gestations were included. Logistic regression analysis was used to adjust for potential confounders between the groups. RESULTS: Among 58,436 women meeting the inclusion criteria, complete outcome data were available for 51,557 (88%), 11,746 (91%) in the amniocentesis group and 39,811 (87%) in the group that did not have amniocentesis. The fetal loss (miscarriages and intrauterine fetal death) rate in the amniocentesis group was 0.4% compared with 0.26% in those without amniocentesis (relative risk 1.6, 95% confidence interval [CI] 1.1–2.2). Fetal loss less than 24 weeks (including induction for ruptured membranes and oligohydramnios) occurred in 0.97% of the amniocentesis group and 0.84% of the group with no procedure (P=.33). The fetal loss rate less than 24 weeks attributable to amniocentesis was 0.13% (95% CI –0.07 to 0.20%) or 1 in 769. The only subgroup that had a significantly higher amniocentesis attributable fetal loss rate was women with a normal serum screen (0.17%, P=.03). CONCLUSION: The institutional fetal loss rate attributable to amniocentesis is 0.13%, or 1 in 769 at Washington University School of Medicine. The total fetal loss rate was not significantly different from that observed in patients who had no procedure. LEVEL OF EVIDENCE: II

Evaluating the Rate and Risk Factors for Fetal Loss After Chorionic Villus Sampling

OBJECTIVE: To estimate the fetal loss rate in our center and evaluate the risk factors associated with such losses after chorionic villus sampling (CVS). METHODS: This is a retrospective cohort study including all women undergoing chorionic villus sampling and a control group that had no invasive procedure at a single center over a 16-year period. Fetal loss was defined as any loss before 24 weeks of gestation. Univariable and multiple logistic regression analyses were used to compare pregnancies resulting in fetal loss to those without a loss and to adjust for potential confounders between the groups. RESULTS: Of 5,243 women who had CVS who were compared with 4,917 women seen before 14 weeks who had no invasive procedure, there were 138 (2.7%) fetal losses before 24 weeks of gestation in the CVS group compared with 161 (3.3%) in the control group (relative risk 0.80, 95% confidence interval, 0.64–1.0). The difference in loss rate of –0.7% (95% confidence interval, –0.02 to 1.3) between the CVS group and those who had no procedure was not statistically significant at P<.05. The significant risk factors for fetal loss were African-American maternal race, at least two aspirations/needle insertions, heavy bleeding during CVS, maternal age younger than 25 years, and gestational age at performing CVS before 10 weeks. CONCLUSION: The estimated fetal loss rate after CVS was not significantly different from the group that had no procedure. Significant predictors of fetal loss after CVS were identified, but the accuracy of the final model for predicting fetal loss was only modest. LEVEL OF EVIDENCE: II

Predicting the risk of pre-eclampsia between 11 and 13 weeks gestation by combining maternal characteristics and serum analytes, PAPP-A and free β-hCG

To determine if a simplified model for predicting pre‐eclampsia (PEC) can be developed by combining first‐trimester serum analytes, pregnancy‐associated plasma protein A (PAPP‐A) and free beta human chorionic gonadotrophin (β‐hCG), and maternal characteristics.

Umbilical Artery Doppler Indices in Small for Gestational Age Fetuses Correlation With Adverse Outcomes and Placental Abnormalities

Objective. The purpose of this study was to compare the screening efficiency of the umbilical artery systolic to diastolic ratio (S/D), pulsatility index (PI), and absent end‐diastolic flow (AEDF) for adverse pregnancy outcomes and placental abnormalities in small for gestational age (SGA) fetuses. Methods. We conducted a retrospective cohort study of Doppler examinations of 161 nonanomalous SGA fetuses. The reliability of the S/D and PI were quantified by intraclass correlation coefficients. The association of the S/D, PI, and AEDF with adverse outcomes and placental abnormalities was compared by the χ2 test. Results. There was a simple association of Doppler results with adverse outcomes, which was mitigated when controlled for gestational age. For all measures of adverse outcomes, the specificity of abnormal Doppler results exceeded the sensitivity, and the negative predictive value was greater than the positive predictive value. Comparing the S/D with the PI, there was no significant difference in the sensitivity; however, the specificity of the PI was at least 90% and exceeded that of the S/D for all outcomes. The intraclass correlation coefficients of the S/D and PI were similar, indicating no difference in reliability. Placental abnormalities were significantly more common in cases with abnormal Doppler values (positive predictive value, 94%) with no overlap in the types of placental lesions in most cases. Conclusions. As an initial screen for adverse outcomes in SGA fetuses, the umbilical artery Doppler S/D, PI, and AEDF were imprecise. However, these measures were all strongly and similarly predictive of placental abnormalities, especially lesions of maternal underperfusion and fetal vascular obstruction.

The efficiency of first-trimester serum analytes and maternal characteristics in predicting fetal growth disorders

OBJECTIVE To evaluate the association between first-trimester serum analytes, pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin, and fetal growth disorders, and to determine whether a prediction model for these growth disorders can be developed. STUDY DESIGN Retrospective cohort study of patients seen for first-trimester aneuploidy screening. Pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin multiples of the median were evaluated for association with small- and large-for-gestational-age infants in combination with maternal characteristics. Univariate and backward stepwise logistic regression analyses were performed and the area under the receiver-operator curves used to determine the best prediction models. RESULTS Neither pregnancy-associated plasma protein A nor free beta-human chorionic gonadotropin levels were associated with an increased risk of large-for-gestational-age infants. For small-for-gestational-age infants, the final model included black race, free beta-human chorionic gonadotropin multiples of the median >90th percentile, and pregnancy-associated plasma protein A multiples of the median <5th percentile as significant predictors (area under the curve = 0.58). CONCLUSION Low pregnancy-associated plasma protein A and high free beta-human chorionic gonadotropin levels are associated with a small-for-gestational-age growth pattern; however, additional factors to improve the prediction model are needed.

Evaluating the incidence and likelihood ratios for chromosomal abnormalities in fetuses with common central nervous system malformations

OBJECTIVE To determine the incidence and likelihood ratios for chromosomal abnormalities in fetuses with common central nervous system malformations on ultrasound. STUDY DESIGN A database derived retrospective cohort study of all patients referred for ultrasound and genetic evaluation from 1990-2006. Fetal karyotypes were delineated by prenatal diagnosis or postnatal examination. The incidence and likelihood ratios were calculated for the association of each central nervous system abnormality with trisomy 13, 18, and 21. RESULTS Of 62,111 women included, 587 (0.9%) had major fetal central nervous system abnormalities. The only central nervous system anomalies associated with trisomy 21 were ventriculomegaly and choroid plexus cysts. When isolated, only spina bifida, holoprosencephaly, and agenesis of the corpus callosum were significantly associated with trisomy 13, anencephaly with trisomy 18, and ventriculomegaly with trisomy 21. Likelihood ratios positive range from 2-20 depending on the central nervous system malformation and aneuploidy type. CONCLUSION Central nervous system malformations detected on ultrasound are strongly associated with and predictive of chromosomal abnormalities, especially trisomy 13 and 18.

Teratology: Principles and Practice

Gross anomalies of structure and/or function affect 2 to 4 per cent of all human newborns and are the leading cause of perinatal mortality in this country. Despite their significance, the etiology of most such defects remains unclear. A majority are unassociated with any identifiable cause; a small but significant percentage are attributed to heritable disorders of either a Mendelian (single gene) or chromosomal nature. Drugs and environmental exposures are currently implicated in only a small percentage of affected pregnancies. Nevertheless, an awareness of the principles of teratogenesis, an appreciation for the role--though imprecise--of placental transfer and fetal drug disposition, and avoidance of known teratogens currently offers our best hope for the study and prevention of birth defects.

The Type and Frequency of Fetal Renal Disorders and Management of Renal Pelvis Dilatation

Objective. This study describes the frequency of sonographically detected fetal renal disorders, the correlation of fetal renal pelvis dilatation (RPD) with the need for postnatal surgery, and proposed management of RPD. Methods. The study population consisted of 342 fetuses with prospectively identified isolated renal abnormalities and known follow‐up. Fetuses with RPD were considered separately with respect to underlying renal disease, postnatal testing, and the need for surgical correction. Obstructive RPD was defined as the need for surgical treatment. Nonobstructive RPD included those cases that required no therapy. The correlation between prenatal RPD and the need for postnatal evaluation was examined. Results. Renal pelvis dilatation was the primary postnatal sonographic finding in 66.4% of cases. The remainder were distributed between multicystic dysplastic kidney, duplication malformations, and reflux, with a smaller number of other diagnoses. Renal pelvis dilatation in the obstructive group was significantly greater than in the nonobstructive group. However, 10% of fetuses with maximum RPD of 10 mm or less had an obstructive process, whereas 58% of fetuses with RPD of greater than 10 mm did not have obstruction. There were no cases in which preterm delivery was necessitated by RPD. Conclusions. Renal pelvis dilatation is the most common fetal renal abnormality. The greater the RPD, the more likely it is due to obstruction. However, the overlap between obstruction and no obstruction dictates postnatal evaluation. In that RPD, regardless of degree, did not change the timing of delivery, a single follow‐up sonographic examination either late in pregnancy or after delivery is considered adequate for follow‐up of RPD detected earlier in pregnancy.

Cocaine inhibits alanine uptake by human placental microvillous membrane vesicles

OBJECTIVE The aim of this study was to determine the effects of cocaine on alanine uptake by human placental microvillous membrane vesicles and to characterize cocaine binding to the microvillous membrane. STUDY DESIGN Microvillous vesicles were isolated from the placentas of 10 human pregnancies with no history of cocaine use. The binding of tritiated cocaine to microvillous vesicle membrane and uptake of tritiated cocaine and tritiated alanine were determined with the use of filtration assays. Scatchard analyses were used to characterize cocaine binding. Sodium-independent and sodium-dependent uptake of tritiated alanine was measured in the presence and absence of (-)cocaine and its stereoisomer (+)cocaine. Uptakes were compared with the use of Student t tests. RESULTS Specific tritiated cocaine binding accounted for approximately 96% of total binding at a single-component high-affinity site in the microvillous membrane. The mediated sodium-dependent component of alanine uptake was significantly (p < 0.01) reduced in the presence of (-)cocaine but was unaffected by (+)cocaine. CONCLUSION Cocaine may contribute to fetal growth restriction by interfering with the normal activity of placental amino acid transporters necessary to maintain the nutrient gradients associated with normal fetal growth.

Universal cervical length screening: implementation and outcomes

BACKGROUND Transvaginal measurement of cervical length (CL) has been advocated as a screening tool to prevent preterm birth, but controversy remains regarding the overall utility of universal screening. OBJECTIVE We aimed to evaluate the acceptability of a universal CL screening program. Additionally we evaluated risk factors associated with declining screening and subsequent delivery outcomes of women who accepted or declined screening. STUDY DESIGN This was a retrospective cohort study of transvaginal CL screening at a single institution from July 1, 2011, through December 31, 2014. Institutional protocol recommended transvaginal CL measurement at the time of anatomic survey between 17-23 weeks in all women with singleton, viable pregnancies, without current or planned cerclage, with patients able to opt out. Patients with CL ≤20 mm were considered to have clinically significant cervical shortening and were offered treatment. We assessed acceptance rate, risk factors for declining CL screening, and the trend of acceptance of CL screening over time. We also calculated the prevalence of CL ≤25, ≤20, and ≤15 mm, and estimated the association between CL screening and spontaneous preterm birth. RESULTS Of 12,740 women undergoing anatomic survey during the study period, 10,871 (85.3%; 95% confidence interval [CI], 84.7-85.9%) underwent CL screening. Of those, 215 (2.0%) had a CL ≤25 mm and 131 (1.2%) had a CL ≤20 mm. After the first 6 months of implementation, there was no change in rates of acceptance of CL screening over time (P for trend = .15). Women were more likely to decline CL screening if they were African American (adjusted odds ratio [aOR], 2.17; 95% CI, 1.93-2.44), obese (aOR, 1.18; 95% CI, 1.06-1.31), multiparous (aOR, 1.45; 95% CI, 1.29-1.64), age <35 years (aOR, 1.24; 95% CI, 1.08-1.43), or smokers (aOR, 1.42; 95% CI, 1.20-1.68). Rates of spontaneous preterm birth <28 weeks were higher in those who declined CL screening (aOR, 2.01; 95% CI, 1.33-3.02). CONCLUSION Universal CL screening was implemented successfully with 85% of women screened. Overall incidence of short cervix was low and women with significant risk factors for preterm birth were more likely to decline screening. Patients who declined CL screening were more likely to be African American, obese, multiparous, age <35 years, and smokers. Rates of early, but not late, spontaneous preterm birth were significantly higher among women who did not undergo CL screening.