Steven L. Warsof

Overview of the impact of noninvasive prenatal testing on diagnostic procedures

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell‐free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high‐risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure‐related fetal losses. Yet, NIPT has been described as a ‘disruptive innovation’ due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome.

Uptake of noninvasive prenatal testing at a large academic referral center.

OBJECTIVE Noninvasive prenatal testing (NIPT) is a recently developed risk-assessment technique with high sensitivity and specificity for fetal aneuploidy. The effect NIPT has had on traditional screening and diagnostic testing has not been clearly demonstrated. In this study, NIPT uptake and subsequent changes in the utilization of first-trimester screen (FTS), chorionic villus sampling (CVS), and amniocentesis in a single referral center is reported. STUDY DESIGN Monthly numbers of NIPT (in high-risk patients), FTS, CVS, and amniocentesis were compared between a 35-month baseline period (April 2009 through February 2012) before introduction of NIPT, and the initial 16 months following NIPT introduction divided in 4-month quarters beginning in March 2012 through June 2013. RESULTS A total of 1265 NIPT, 6637 FTS, 251 CVS, and 1134 amniocentesis were recorded over the 51-month study period in singleton pregnancies of women who desired prenatal screening and diagnostic testing. NIPT became the predominant FTS method by the second quarter following its introduction, increasing by 55.0% over the course of the study period. Total first-trimester risk assessments (NIPT+FTS) were not statistically different following NIPT (P = .312), but average monthly FTS procedures significantly decreased following NIPT introduction, decreasing by 48.7% over the course of the study period. Average monthly CVS and amniocentesis procedures significantly decreased following NIPT introduction, representing a 77.2% and 52.5% decrease in testing, respectively. Screening and testing per 100 morphological ultrasounds followed a similar trend. CONCLUSION NIPT was quickly adopted by our high-risk patient population, and significantly decreased alternate prenatal screening and diagnostic testing in a short period of time.

Association of combined first-trimester screen and noninvasive prenatal testing on diagnostic procedures.

OBJECTIVE: To describe the changes over a 9-year period in the number and rate of diagnostic testing after the introduction of the combined first-trimester screen and subsequent noninvasive prenatal testing. METHODS: The number of prenatal screening and diagnostic tests was recorded over a 9-year period from billing records. Three time intervals were considered: 1) 20 months before a combined first-trimester screen was offered; 2) 72 months after a combined first-trimester screen was offered; and 3) 16 months after noninvasive prenatal testing introduction. Prenatal testing was compared per year, per time interval, and per 100 morphologic ultrasonograms to account for fluctuations in patient number. RESULTS: A total of 15,418 prenatal tests was recorded during the study period, consisting of 9,780 combined first-trimester screen, 1,265 noninvasive prenatal testing, 608 chorionic villus sampling (CVS), and 3,765 amniocenteses. Combined first-trimester screen peaked at 1,836 in 2009–2010 but declined by 48.1% after noninvasive prenatal testing was introduced. Combined first-trimester screen per 100 morphologic ultrasonograms also significantly decreased (P<.05) after noninvasive prenatal testing introduction. Chorionic villus sampling peaked after combined first-trimester screen introduction in 2007–2008 with 100 procedures, representing an 81.8% increase from prefirst-trimester screen. After the introduction of noninvasive prenatal testing, CVS declined by 68.6% during 2012–2013. Chorionic villus sampling per 100 morphologic ultrasonograms followed the same trend. Amniocentesis declined every year of the study period (78.8% overall), including 60.3% after combined first-trimester screen and a further 46.7% after noninvasive prenatal testing. Monthly amniocentesis procedures per 100 morphologic ultrasonograms significantly decreased (P<.05) after introduction of a combined first-trimester screen and noninvasive prenatal testing. CONCLUSION: The introduction of combined first-trimester screen was associated with an increase in CVS and a decrease in amniocentesis testing. Noninvasive prenatal testing was associated with a subsequent decrease in CVS and further decrease in amniocentesis. LEVEL OF EVIEDENCE: III

Fetal Sacrococcygeal Teratoma

The fetus with sacrococcygeal teratoma (SCT) is at high risk for prenatal and perinatal complications. The natural history and pathophysiology of fetal SCT is different than that of postnatally diagnosed SCT, and has only recently been defined. Survival of fetuses with SCT is dependent on anticipation and recognition of pathophysiologic events, and optimal obstetric and surgical management. In a subset of fetuses with SCT, fetal resection of tumor may offer the only hope for survival.

Doppler analysis of the umbilical artery. The importance of choosing the placental end of the cord.

Thirty normal pregnancies were studied with continuous or pulsed Doppler ultrasound (50 measurements). The ratio of systolic (S) to end‐diastolic (D) measurement, or S/D ratio, was obtained at both ends of the cord: the placental insertion and the fetal abdominal insertion. A statistically significant difference was demonstrated between the two sets of measurements. Normal values were obtained at the placental insertion, whereas, simultaneously, the fetal abdominal insertion generated highly abnormal values. When performing Doppler waveform analysis of the umbilical artery, if abnormal values are obtained, one should be cautious to be certain that they originated from the placental insertion.

Lower Limb Movements and Urologic Function in Fetuses with Neural Tube and Other Central Nervous System Defects

Lower limb movements and urologic systems were evaluated by prenatal ultrasound in 120 fetuses with either neural tube defects or intracranial anomalies. Despite anticipated major lower extremity and bladder dysfunction, lower limb movements were seen in 100% of the fetuses with anencephaly and encephaloceles, 93% with isolated spina bifida, 60% with complex spina bifida and 90% with abnormal intracranial findings. In all the cases except those with cloacal exstrophy, fetal bladder and collecting systems appeared normal. Therefore, fetal lower limb movements and urinary tract integrity appear to have no diagnostic or prognostic value in fetuses with neural tube defects or other central nervous system anomalies. These diagnoses can only be made by direct ultrasound observation of the lesion itself.

Cook obstetrics and gynecology catheter multicenter chorionic villus sampling trial: Comparison of birth defects with expected rates

OBJECTIVE The null hypothesis was that offspring of women undergoing first-trimester chorionic villus sampling do not experience a rate of birth defects exceeding background rates. STUDY DESIGN Follow-up information regarding major malformations was prospectively sought on offspring of 4105 women undergoing first-trimester chorionic villus sampling from nine centers participating in a collaborative study with the Cook obstetrics and gynecology catheter. These data were compared with data from the Collaborative Perinatal Project and other registries. RESULTS A total of 84 offspring with major malformations was identified (2.36%). Compared with background rates, there was no increase in the incidence of total malformations or specific malformations (including limb reduction defects) in the subjects. One institution experienced all three limb reduction defects in this series; the probability of this occurring by chance alone is < 1%. CONCLUSION Chorionic villus sampling was not found to result in an increase in major birth defects or in specific categories of birth defects in this series.

Fetal biometry: Relevance in obstetrical practice

Fetal biometry is the measurement of the fetus and various segments of the fetal anatomy. Every part of the fetal anatomy may be imaged, but fetal head, abdomen, and femur measurements are the most commonly used, as well as the crown-rump length in early gestation. These biometric measurements can be used to estimate gestational age and fetal weight, evaluate interval fetal growth, and identify fetuses who are either growth restricted or macrosomic. These measurements may influence antepartum and intrapartum management and may be used to predict peripartum outcomes. Biometry is therefore an integral and valuable element of obstetrical practice.

Ultrasonic Prediction of Discordant Growth in Twin Pregnancies

In this prospective study conducted from 1984 through 1987, the ability to correctly predict growth discordancy in twin gestations by ultrasonic estimated fetal weights is examined. Discordancy was defined as an intertwin birth weight difference of 25% or greater. This method resulted in a sensitivity rate of 77% and a specificity rate of 92%. The positive predictive value of an abnormal test (i.e. discordant growth) was 67% and the negative predictive value of a normal test (i.e. concordant growth) was 95%. The perinatal mortality rate of 217/1,000 in discordant twin fetuses was significantly higher than 29/1,000 in the concordant twins in this study population (p < 0.01) and even more of a contrast to the rate of 10/1,000 in our singleton population. Accurate prediction of discordant twin pregnancies which are at high risk for poor outcome opens the opportunity for potential in utero treatment modalities.

Counseling for Fetal Macrosomia: An Estimated Fetal Weight of 4,000 g is Excessively Low

OBJECTIVE Because of the known complications of fetal macrosomia, our hospitals policy has been to discuss the risks of shoulder dystocia and cesarean section (CS) in mothers with a sonographic estimated fetal weight (SEFW) ≥ 4,000 g at term. The present study was performed to determine the effect of this policy on CS rates and pregnancy outcome. STUDY DESIGN We examined the pregnancy outcomes of the macrosomic (≥ 4,000 g) neonates in two cohorts of nondiabetic low risk women at term without preexisting indications for cesarean: (1) SEFW ≥ 4,000 g (correctly suspected macrosomia) and (2) SEFW < 4,000 g (unsuspected macrosomia). RESULTS There were 238 neonates in the correctly suspected group and 205 neonates in the unsuspected macrosomia group, respectively. Vaginal delivery was accomplished in 52.1% of the suspected group and 90.7% of the unsuspected group, respectively, p < 0.001. There was no difference in the rates of shoulder dystocia. The odds ratio for CS was 9.0 (95% confidence interval, 5.3-15.4) when macrosomia was correctly suspected. CONCLUSION The policy of discussing the risk of macrosomia with SEFW ≥ 4,000 g to women is not justified. A higher SEFW to trigger counseling for shoulder dystocia and CS, more consistent with American College of Obstetrics and Gynecology (ACOG) guidelines, should be considered.