Are isolated facial cleft lip and palate associated with increased perinatal mortality? A cohort study from the West Midlands Region, 1995-1997.

OBJECTIVE: To investigate the association between cleft lip and/or palate and perinatal mortality. METHODS: A retrospective review was performed of cases of cleft lip/palate born to West Midlands residents from 1995 to 1997. Perinatal mortality for identified cases was compared with all births from 1995 to 1997. RESULTS: 347 cases of cleft lip and/or cleft palate were delivered from 1995 to 1997. Thirty-six pregnancies were terminated due to parental wishes--2 were registerable births. There were 310 spontaneous registerable births (stillbirths/livebirths) with cleft lip and/or palate and 1 further late fetal loss. In 220 (70.5%), the lesion was isolated. Of these, there were 7 perinatal deaths, 5 had post mortems and no additional anomalies were identified. In 92 (29.5%) cases other abnormalities were identified. The overall perinatal mortality rate (PNMR) in the West Midlands, was 10.0/1000 total births. The overall PNMR for babies with facial clefts was 89.7/1000 total births. The PNMR for those with associated anomalies was 228.3/1000 live/still births. The PNMR for isolated facial clefts was 31.8/1000 live/still births, significantly higher than the background population (OR 3.3, 95% CI: 1.5-7.0). CONCLUSION: Consideration should be given to screening the fetus at 20-24 weeks for facial deformity. This has implications for detection both of fetal anomalies and of a population at risk for adverse outcome.     

Audit of perinatal deaths in a tertiary level hospital in Latvia (1995–1999) using the Nordic-Baltic perinatal death classification: Evidence of suboptimal care

Objective.?The objective of this study was to explore applicability of the Nordic-Baltic perinatal death (PND) classification in a single hospital via evaluation of changes of the preventability of PND over the time period in a tertiary level perinatal care center in Latvia.

Method.?All PND cases during the period 1995–1999 at a tertiary referral perinatal care center, the Riga Maternity Hospital (RMH), were analyzed using the common Nordic-Baltic PND classification.

Results.?The total perinatal mortality rate (PNMR) did not decline at the RMH over the study period. The rate of antenatal and intrapartum deaths at <28 weeks of gestation increased (p < 0.01). Early neonatal deaths at 28–33 weeks of gestation with a low 5-minute Apgar score became less frequent (p < 0.05). There was a trend towards more cases of probably suboptimal care (p < 0.005) and the proportion of preventable PND cases increased from 14.7% in 1995 to 36.4% in 1999 (p = 0.01).

Conclusion.?The perinatal audit performed at the RMH using the Nordic-Baltic PND classification disclosed a requirement for further improvement of perinatal care in the hospital. The classification can be used to evaluate the preventability of perinatal death cases in a single hospital, and its application in other hospitals in Latvia could provide information necessary for the improvement of perinatal care in the country.     

Evaluation of prenatal diagnosis of cleft lip with or without cleft palate and cleft palate by ultrasound: experience from 20 European registries. EUROSCAN study group

Ultrasound scans in the mid-trimester of pregnancy are now a routine part of antenatal care in most European countries. Using data from registries of congenital anomalies a study was undertaken in Europe. The objective of the study was to evaluate prenatal detection of cleft lip with or without cleft palate (CL(P)) and cleft palate (CP). All CL(P) and CPs suspected prenatally and identified at birth in the period 1996-98 were registered from 20 Congenital Malformation Registers from the following European countries: Austria, Croatia, Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands, UK, Ukraine. These registries followed the same methodology. A total of 709,027 births were covered; 7758 cases with congenital malformations were registered. Included in the study were 751 cases reported with facial clefts: 553 CL(P) and 198 CP. The prenatal diagnosis by transabdominal ultrasound of CL(P) was made in 65/366 cases with an isolated malformation, in 32/62 cases with chromosomal anomaly, in 30/89 cases with multiple malformations and in 21/36 syndromic cases. The prenatal diagnosis of CP was made in 13/198 cases. One hundred pregnancies were terminated (13%); in 97 of these the cleft was associated with other malformations.     

Prenatal evaluation of facial clefts with two-dimensional and adjunctive three-dimensional ultrasonography: a prospective trial

OBJECTIVE: The purpose of this study was to compare the prenatal diagnostic capabilities of two-dimensional ultrasonography versus adjunctive three-dimensional ultrasonography for fetal cleft lip and palate. STUDY DESIGN: Fetuses that were suspected of a facial cleft were then examined sequentially with two-dimensional ultrasonography then with a targeted scan of the fetal face with three-dimensional ultrasonography. The images were coded as cleft, no cleft, or equivocal for lip and palate. Postnatal outcome follow-up was obtained. RESULTS: Fifty-three of 57 fetuses had outcome results available. The diagnostic accuracy (true positive + true negative) of adjunct three-dimensional ultrasonography versus two-dimensional ultrasonography alone were improved for cleft lip (100% [53/53 fetuses] vs 91% [48/53 fetuses], P <.05) and cleft palate (89% [47/53 fetuses] vs 57% [30/53 fetuses], P <.05) CONCLUSION: There is significant improvement in diagnostic accuracy with two-dimensional ultrasonography with adjunctive three-dimensional ultrasonography compared with two-dimensional ultrasonography alone for the prenatal evaluation of facial clefts.     

Prenatal imaging of facial clefts by magnetic resonance imaging with emphasis on the posterior palate

OBJECTIVE: To evaluate the role of Magnetic Resonance Imaging (MRI) in the prenatal diagnosis of facial clefts. MATERIALS AND METHODS: Six fetuses with a sonographic diagnosis of cleft lip and palate underwent MRI at a median age of 30 weeks (range 28-32). The defect was bilateral in two cases. RESULTS: Fetal MRI confirmed the presence of a cleft involving at least the anterior palate in all cases. Distinction between unilateral and bilateral clefts could be made in all cases and was always confirmed after birth. Sagittal views of the fetal face were found to be particularly useful in identifying the degree of extension of the cleft into the palate. The diagnosis was confirmed after birth. CONCLUSION: Our results suggest that MRI may be ancillary to ultrasound in prenatal investigation of a fetus with cleft lip, allowing a better staging of the lesion by demonstrating the degree of involvement of the palate.     

Chromosomal defects and associated malformations in fetal cleft lip with or without cleft palate

OBJECTIVE: To describe the incidence, associated features including chromosomal defects in fetuses, with cleft lip and/or palate and assess the need for karyotyping. METHODS: Retrospective study of 62 cases of prenatally diagnosed facial cleft lip and/or palate in a tertiary fetal medicine unit between January 1991 and December 1999. Chromosome analysis was performed in all fetuses with associated ultrasound findings and in 14 (39%) fetuses with isolated facial clefts. RESULTS: Associated abnormalities were detected in 26 (42%) of the 62 fetuses of which 22 (35%) fetuses had multiple other abnormalities. Central nervous system abnormalities and limb malformations were the most common. Three fetuses had genetic syndromes confirmed after birth. All fetuses with isolated clefts were chromosomally normal, whereas 15 of the 26 with additional abnormalities (58 or 24% of the total group) had chromosomal defects (eight cases of trisomy 13, five of trisomy 18, one unbalanced translocation between chromosomes 7 and 8, and one deletion 4p-). All 22 women who chose not to undergo fetal karyotype analysis delivered phenotypically normal infants. There were five midline clefts; each of them was associated with additional sonographic findings and four were associated with holoprosencephaly. CONCLUSION: Isolated facial clefting is not associated with an increased risk for chromosomal defect. Amniocentesis is recommended when facial cleft is found in association with additional ultrasonographic abnormalities as it is unnecessary for isolated clefts.     

综合征性神经管缺陷3 798例分析

目的：探讨综合征性神经管缺陷（neural tube defects,NTDs）的发生形式和伴发畸形谱。方法：中国出生缺陷监测网采用以医院为基础的监测方法,收集1987-1995年间,孕28周到产后7d,伴各种出生缺陷的围产儿资料,包括活产、死胎和死产。结果：3498例综合征性NTDs,无脑、脊柱裂和脑膨出分别为997例、2394例和407例。伴发肌肉、骨骼系统,面、耳、颈部和泌尿生殖系统畸形的围产儿分别为51.3％,19.6％和9.3％。前5位高发畸形分别是马蹄内翻足、唇腭裂（唇裂合并腭裂）、腹裂、足外翻、足月睾丸未降。神经管缺陷的裂联合征（schisis-association）中,NTDs合并总唇裂（唇裂 唇裂合并腭裂）占67.5％,无脑合并腭裂占8.3％,无脑合并脐膨出占6.6％。综合征性NTDs患儿低出生体重儿发生率为36.9％,围产期病死率为71.2％,产前诊断率为33.1％。结论：为1/3的NTDs可伴发其他畸形。综合征性NTDs儿病死率高,预后差。     

Role of fetal autopsy as a complementary tool to prenatal ultrasound

Abstract

Aim: To correlate and compare prenatal ultrasound with fetal autopsy examination to detect structural births defects and provide specific diagnoses.

Methods: 141 second trimester fetuses (<20 weeks and <500?g) where pregnancy was terminated for structural birth defects and/or severe intra-uterine growth restriction (IUGR) or intra-uterine death, referred to our tertiary care private, teaching hospital were examined by a team of experienced pathologist and clinical geneticist. Findings of pathology examination were compared to those provided by ultrasound examination.

Results: A total of 301 structural abnormalities were noted. Specific etiology was identified or syndromic diagnosis was possible in 57/141 (40.4%) cases. The maximum number of systemic anomalies (45/301, 14.95%) was noted in the central nervous system (CNS). CNS anomalies were most commonly associated with facial dysmorphism including cleft lip/palate etc. There was a complete agreement between ultrasound and autopsy findings in 41/141 (29.07%) cases, additional information that did not influence the final diagnosis and/or counseling was obtained by autopsy in 65/1416 (46.09%) cases, while additional information that influenced the final diagnosis and/or counseling was provided by autopsy in 35/141 (24.82%) cases.

Conclusion: Fetal autopsy serves as a complementary tool to fetal ultrasound due to its ability to pick up minor anomalies and/or anomalies that were missed on ultrasound. It may be routinely performed as an attempt to reach a specific diagnosis and offer appropriate counseling to couples, following pregnancy termination for fetal anomalies.     

Prenatal diagnosis of cleft palate by 3D ultrasound

A case of a fetus seen at 33.2 weeks of gestation who was diagnosed with cleft lip in the third quarter by routine ultrasound. Describes the sequential steps that led to a multidisciplinary support the diagnosis of cleft palate by three-dimensional image reconstruction, which were originally obtained to demonstrate the fetal face surface. Birth confirmed the prenatal findings and established the diagnosis of cleft lip and cleft hard and soft palate. It has been reported that the diagnosis of facial clefts can be done with relative ease prenatally, but the detection rate of facial clefts in routine tests is only 20%. Until recently the diagnosis of cleft palate is not considered possible, however in recent years advances in three-dimensional technology has made possible the development of techniques for the assessment of the palate and various authors have reported promising results of ingenious applications that make think that in the near future will approach the palate a fact. We discuss the advantages and disadvantages of these methods are relatively new and highlights how valuable this information is for parents of the affected creature.     

Pregnancy complications in women with heart disease

Objective.?To identify pregnancy complications of women with heart disease delivering at a university hospital.

Methods.?A retrospective study was carried out of 193 pregnant women with heart disease delivered at a university hospital between January 1997 and December 2006.

Results.?Rheumatic heart disease (RHD), congenital heart disease (CHD), arrhythmia and cardiomyopathy were observed in 133 (68.9%), 26 (13.5%), 32 (16.6%) and 2 (1%) cases, respectively. Obstetric complication was found in 27 (14%) cases that was composed of preterm delivery (11.4%), gestational diabetes (1%), pregnancy induced hypertension (1%) and postpartum hemorrhage (0.5%). Cardiac complication was observed in 24 (12.4%) cases. Congestive heart failure was the most common cardiac complication which observed in 11 (5.7%) cases. There were four (2.1 %) maternal deaths, three cases in CHD group and one case in RHD group. Preterm infant was observed in 22 (11.4%) cases. Thirteen percent had low birth weight and 8.3% were small for gestational age. There were no perinatal deaths or congenital anomalies.

Conclusion.?Form this study, RHD with pregnancy is still predominant. The most common obstetric complication was preterm delivery. The most common cardiac complication was congestive heart failure.     

Birth defects data from surveillance hospitals in Dalian city,China, 2006–2010

Objective: The objective of this study is to disclose characteristics of birth defects in perinatal infants in Dalian and provide an epidemiological basis for controlling birth defects.

Methods: Data used in this study were collected from surveillance hospitals in Dalian during 2006–2010. Comparison analysis and trend analysis were conducted by performing Chi-square tests.

Results: The perinatal prevalence of birth defects from 2006 to 2010 was 101.14 per 10?000 live births and was decreased by about 29% from 115.49 per 10?000 live births in 2006 to 81.16 per 10?000 live births in 2010. The prevalence in urban was higher than that in rural areas significantly. The three leading birth defects were congenital heart disease, cleft lip and/or palate, and polydactyly or syndactyly. About 572 cases identified by antenatal diagnosis were terminated pregnancy before 28 weeks of gestation, so the prevalence of birth defects would decrease from 126.29/10?000 to 101.14/10?000.

Conclusions: Dalian has experienced a decreasing temporal trend of birth defects’ prevalence; however, it is still confronted with the challenge to reduce the prevalence of birth defects. Congenital heart diseases are the focus to prevent birth defects. It is necessary to keep the surveillance system function properly, provide preconception health care service extensively, and improve the ability of prenatal diagnosis.     

Prenatal detection of facial clefts

OBJECTIVES: To determine (1) the antenatal detection rate for isolated cleft lip and/or cleft palate during the routine anomaly scan; (2) the correlation between prenatal diagnosis and postnatal findings, and (3) the association of apparently isolated cleft lip and/or cleft palate with other anomalies, in particular chromosomal abnormalities. METHOD: A population-based retrospective analysis of all cases of isolated cleft lip and/or cleft during an 8-year period in an academic teaching hospital in the UK. RESULTS: Thirty-nine cases of isolated cleft lip and/or cleft palate were identified among deliveries at the hospital. Twenty-eight cases had a routine anomaly scan. Fourteen cases were detected prenatally (sensitivity 50%). None of the isolated cleft palates was detected, while 14 of 20 cases of cleft lip (70%) were detected. One of the isolated cases of cleft lip was associated with trisomy 21, while 3 of the isolated cleft palate cases were associated with the Pierre Robin syndrome. In all cases, an antenatal diagnosis of cleft was confirmed following delivery or post-mortem examination (specificity 100%). CONCLUSIONS: Ultrasound is a useful tool in screening for cleft lip with or without cleft palate, but not for cleft palate alone. Even with an isolated cleft lip, there is an increased risk of chromosomal abnormality. The role of prenatal education and support is extremely important in the preparation of prospective parents and can help alleviate the shock which occurs when there is an unexpected cleft at birth.     

Protective effect of hyperemesis gravidarum for nonsyndromic oral clefts

OBJECTIVE: To evaluate whether hyperemesis gravidarum is associated with a decreased risk for nonsyndromic oral clefts and to examine the relationship between hyperemesis gravidarum, birth weight, and gestational age. METHODS: This was a population-based, matched case-control study of 1950 subjects with oral clefts (1368 with cleft lip with or without cleft palate; 582 with cleft palate) collected from the Hungarian Congenital Abnormality Registry and 1955 controls identified from the National Birth Registry. RESULTS: Fewer mothers of newborns with oral clefts had early-onset hyperemesis gravidarum than did mothers of controls (cleft lip with or without cleft palate: 83 cases and 121 controls, odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.50, 0.89; cleft palate: 42 cases and 64 controls, OR = 0.63, 95% CI 0.42, 0.94). The use of dimenhydrinate was more common among mothers of subjects with cleft palate (OR = 2.47, 95% CI 1.11, 5.49), whereas iron seemed to have a protective effect against this condition (OR = 0.26, 95% CI 0.09, 0.80). Gestational age and birth weight were not significantly associated with hyperemesis gravidarum. CONCLUSION: This study suggests that hyperemesis gravidarum provides a protective effect against risk to oral clefts in newborns.     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。     

Placental abruption,offspring sex,and birth outcomes in a large cohort of mothers

Objective.?To investigate stillbirth, neonatal, and perinatal death outcomes in pregnancies complicated by placental abruption, according to fetal sex.

Methods.?We utilized maternally linked cohort data files of singleton live births to mothers diagnosed with placental abruption during the period 1989 through 2005 (n?=?10,014). Logistic regression models were employed to generate adjusted odd ratios and their 95% confidence intervals. Male babies served as the referent category.

Results.?The sex ratio at birth was 1.18. The overall prevalence of stillbirth, neonatal mortality, and perinatal mortality was 7.2%, 4.5%, and 11.8%, respectively. Placental abruption was less likely to occur in mothers carrying female pregnancies than mothers of male infants (adjusted odds ratio [95% confidence interval]?=?0.89 [0.86–0.93]). There were no significant sex differences with regards to stillbirth, neonatal mortality, and perinatal mortality. Similar findings were observed for preterm and term infants.

Conclusions.?Although a preponderance of male infants was discernable among mothers with placental abruption, no sex difference in fetal survival was observed among the offspring of the mothers affected by placental abruption.     

Natural history of 70 fetuses with a prenatally diagnosed orofacial cleft

OBJECTIVE: This study is an analysis of neonatal outcome in 70 fetuses diagnosed over a 10-year period as having cleft lip with or without cleft palate (CL-P) by ultrasonographic examination. METHODS: We describe the natural history of these 70 fetuses with orofacial clefts and select those who may be candidates for fetal surgery. The sonograms of 70 fetuses with orofacial clefts were evaluated for the nature of the CL-P and for the nature of the associated anomalies. Additionally, karyotyping was performed in 63 of 70 patients (90%). RESULTS: The frequency of additional anomalies and the mortality rate varied with the type of cleft. Also, the frequency and type of chromosomal abnormalities varied with the type of cleft. The overall mortality rate was 63% (n = 44). 3 of the surviving 26 fetuses had severe associated anomalies. In 13 of the remaining 23 cases, the fetal age at diagnosis (> or =22 weeks) excluded the fetuses from the potential benefits of fetal intervention. CONCLUSION: Of 70 fetuses with prenatally diagnosed orofacial clefts, only 10 (14%) were candidates for fetal CL-P surgery.     

Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000

OBJECTIVES: To describe trends in incidence, associated anomalies, clinical outcomes and sensitivity of prenatal diagnosis for congenital malformations of the diaphragm in the West Midlands Region between 1995 and 2000. METHODS: Information was retrieved from a population-based register of major congenital malformations in a health region of England, the West Midlands Congenital Anomaly Register (WMCAR), between 1995 and 2000. RESULTS: One hundred and sixty-one confirmed cases of congenital malformations of the diaphragm were notified from 396 577 births. This gives an incidence of 4.1 per 10,000 births. After natural losses and terminations, the incidence at birth was 2.9 per 10,000 registered births. For live-born cases, the infant mortality rate was 317 per 1000 births. 47% of the cases had additional structural or chromosomal anomalies; the infant mortality rate for these complex cases was 533 per 1000, an increased relative risk of 2.37 compared with isolated lesions. 66% of the cases were diagnosed prenatally, 51% of isolated lesions and 84% of complex cases. Fourteen prenatally diagnosed cases (12%) were false-positives; however, 11 of these cases had other significant pathology. These 14 cases were not included in the 161 confirmed cases. CONCLUSION: Congenital malformations of the diaphragm remain associated with considerable infant mortality. Most cases are now diagnosed before birth and the prognosis is adversely affected by the presence of other structural or chromosomal anomalies. This presents significant challenges for those involved in counselling the parents of affected fetuses.     

The prenatal diagnosis of Pierre-Robin sequence.

The purpose of this study was to evaluate the spectrum of prenatal sonographic and chromosomal findings, associated anomalies and perinatal and neonatal outcomes in cases with Pierre-Robin sequence. All cases (20) with Pierre Robin sequence, who were born at China Medical College Hospital between 1990 and 1997, were included and analysed in this series. 12 pregnancies (60 per cent) were complicated by polyhydramnios and 9 (45 per cent) were combined with cleft palate. Four cases (20 per cent) with cardiac anomalies were also observed. Two fetuses (10 per cent) had abnormal karyotyping (one trisomy 21, one trisomy 18). All fetuses were delivered at or near term. Male deviation was observed in cases with isolated Pierre-Robin sequence or combined mild anomalies (male female ratio: 13:3). Two neonatal mortalities and three with mental retardation were observed. This investigation provides a basis for counselling patients with fetal micrognathia or neonatal Pierre-Robin sequence. The main prenatal sonographic findings of Pierre-Robin sequence are micrognathia, polyhydramnios and cleft palate. In cases of polyhydramnios, sonographic examination of the facial profile and palate are recommended. After the finding of polyhydramnios, micrognathia, and even cleft palate, clinicians should be aware of the possibility of neonatal Pierre-Robin sequence. Cardiac evaluation and karyotyping is also recommended.     

Impact parental de l’échographie 3D/4D des fentes labiopalatines

ObjectivePrenatal diagnosis of cleft lip and palate has been available for over 25 years. 3D ultrasound has significantly improved prenatal screening and perinatal care. Surface rendering of the fetal face is frequently asked by parents during exam and it has been shown to substantially improve parental-fetal bonding. However, little is known about the parental impact of surface ultrasound of the abnormal fetal face. We thus decided to assess parental feelings after 3D surface rendering of the fetal face in cleft lip and palate.Patient(s) and methodBetween January 2003 and December 2006, a questionnaire was systematically proposed after birth to the parents who had 3D examination during pregnancy for lip and cleft palate. Analysis of results was performed retrospectively.ResultsTwenty-three couples answered to inclusion criteria, 12 have been contacted, 9 responded. 3D ultrasound was not perceived as disturbing in 78% of parents. On the contrary 3D pictures had a positive effect and better prepare parents to birth. All of them even more considered that it should be systematically performed.Discussion and conclusionPrenatal diagnosis of cleft lip and palate is known to improve parental well-being during the perinatal period. Furthermore, in addition to improved diagnosis, 3D ultrasound also provides a better understanding and acceptance of the malformation than 2D examination. The parental impact of 3D ultrasound is positive supporting and strengthening a systematic use in isolated fetal lip and cleft palate.     

Expectant management of preeclampsia superimposed on chronic hypertension

Objective.?Women with chronic hypertension (CHTN) are at an increased risk for pregnancy complications including preeclampsia. The objective of this study was to review pregnancy outcomes for women with expectant management of preeclampsia superimposed on CHTN prior to 37 weeks'.

Methods.?We reviewed the inpatient charts of all women admitted to Magee-Womens Hospital (1995–2005) with the diagnosis of both CHTN and preeclampsia prior to term.

Results.?Sixty-eight women diagnosed with both CHTN and preeclampsia prior to 37 weeks' were identified. Of these, 42 women were expectantly managed; one subject was excluded from analysis for pregestational diabetes. For the remaining 41 women, the median gestational age at diagnosis was 31.6 weeks (range 23.6–36.4). The mean time from diagnosis to delivery was 9.7 days (range 2–34 days). Adverse perinatal outcomes included one case of HELLP syndrome, two cases of placental abruptions, three cases of pulmonary edema, and five postpartum hemorrhages. There were no fetal/neonatal or maternal deaths. Average NICU stay was 17.9 days.

Conclusions.?Expectant management of preterm superimposed preeclampsia among women with CHTN is a reasonable management strategy, but associated with some maternal morbidity. Prospective studies are needed to definitively quantify the risks and benefits of this approach.