46: Fetal anomalies

Fetal anomalies

Ashley T. Peterson and Sabrina D. Craigo

Division of Maternal‐Fetal Medicine, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA, USA

Introduction and background

The presence of fetal anomalies complicate between 2% and 3% of all pregnancies [1]. The World Health Organization estimates that more than a quarter‐million neonatal deaths are associated with congenital anomalies annually worldwide. Major anomalies are an important contributor to chronic illness and disability and can have significant impact on the patient, family, and healthcare system. The most common major anomalies are cardiovascular and neural tube defects. The most common chromosome abnormality associated with anomaly is Trisomy 21, or Down syndrome. Causes can be genetic, infectious, drug‐related or environmental. Some anomalies may be prevented via the avoidance of known or suspected teratogens (alcohol), supplementation of nutrition (folate), administration of vaccines (rubella), or control of chronic maternal illnesses (diabetes). In addition, screening programs exist to improve rates of prenatal detection and aid in parental counseling and guide individual pregnancy management.


Patients with structural ultrasound anomalies, especially more than one major anomaly, should be offered diagnostic testing. In the literature, the risk of chromosome abnormalities in a fetus with major anomalies varies (rates of 2–35% have been reported) and depends on the number and the type of fetal systems involved. A retrospective study at a single institution that included 2806 fetuses with malformations detected on ultrasound found multisystem malformations were associated with a higher rate of abnormal karyotype (29%) than isolated malformations (2%) [2]. Similarly, Rizzo et al. included 425 fetuses with abnormal karyotypes and reported multiple anomalies were more likely to be associated with an abnormal karyotype than an isolated anomaly (35.0% versus 8.9%) [3]. A 2005 retrospective review of a low‐risk population in Belgium reported a statistically significant difference in abnormal chromosomes for fetuses with multiple malformations (18.8%) compared with isolated malformations (9.3%) [4]. Furthermore, isolated malformations of cystic hygroma or hydrops were statistically more likely to be associated with abnormal karyotype compared to all other organ systems (p < 0.001). Conversely, isolated malformations of the urinary tract were significantly less likely to be associated with abnormal karyotype than anomalies of other systems.

Chromosomal microarray analysis has also been studied and reported to improve diagnosis of cytogenetic aberrations in fetuses with structural anomalies over traditional karyotyping. In a prospective multi‐center study, microarray detected clinically relevant deletions or duplications in 6.0% of subjects with anomaly on ultrasound (N = 1109) when the fetal karyotype was normal [5]. This confirms an earlier systematic review that reports microarray detects clinically significant genomic alterations in 5.2% of patients with an ultrasound anomaly and a normal karyotype [6]. Microarray will detect deletions and duplications that will be missed on traditional karyotype, however it will miss inversions and balanced translocations, which are associated with 6.7% (95% confidence limits, 3.1–10.3%) of structural anomalies [7]. Thus, for patients with at least one major structural anomaly on ultrasound, microarray is recommended and can replace fetal karyotype; for patients with normal ultrasound findings, traditional karyotype for prenatal diagnosis is preferred [8].

Associated findings

A retrospective study from a single institution of 250 pregnancies noted to have severe oligohydramnios (anhydramnios) reported fetal anomalies in 50.7% of second‐trimester cases and 22.1% of third‐trimester cases [9]. Severe oligohydramnios was associated with renal anomalies most often (65.2%). Similarly, a 2011 single‐institution retrospective study of 28 555 third‐trimester ultrasounds reported major fetal malformations were more common in pregnancies with oligohydramnios (25%) and borderline amniotic fluid index (AFI) (10%) than normal AFI (2%), p < 0.001 [10].

The presence of a single umbilical artery has been known to be associated with congenital anomalies, but the degree of association varies depending on the study design. A meta‐analysis that included studies spanning four decades found a 27% incidence of congenital malformation associated with a single umbilical artery among live‐born singleton pregnancies, 7% of which were major renal anomalies [11]. Additionally, when the analysis expanded the sample from live‐born pregnancies to include fetal autopsies, abortions and demised fetuses, single‐umbilical cord arteries were associated with congenital anomalies in two‐thirds of cases. A large Canadian population‐based study found single umbilical artery occurred in 0.44% of singleton pregnancies and was associated with an almost sevenfold increased risk of co‐occurring fetal anomalies, with genitourinary anomalies being most common [12]. A smaller, single‐institution retrospective cohort study of singleton pregnancies undergoing routine anatomic survey found fetuses with a single umbilical artery were associated with significantly increased risk of renal and cardiac malformations, with adjusted odds ratios of 3.0 and 21.0 respectively [13].

Twinning is associated with an increased risk of congenital anomalies. Data from the 1980 Metropolitan Atlanta Congenital Defects Program reported that twins have almost a 50% higher likelihood of anomalies, and even more so with same‐sex (likely monozygous) twinning [14]. An analysis of nine international registries reported an overall congenital malformation relative risk of 1.25 (95% CI, 1.21–1.28) in twins compared with singletons [15]. Additionally, this study reported anomalies were more likely to occur in twin pregnancies across all systems. Rates of cardiac anomalies in particular have been reported as occurring more frequently in twin gestations. One population‐based study in Northern Ireland reported increased rates of fetal cardiovascular system anomalies in same‐sex twins (91.0/10 000) versus singletons (66.4/10 000) [16]. A smaller study of twins from Spain reported similar overall rates of fetal anomalies in twins and singletons, but significantly higher relative risk of central nervous system (CNS), cardiovascular system, and genitourinary system anomalies in same‐sex twins than singletons [17].


Ultrasound screening is used to detect anomalies before birth. Three large trials (the Eurofetus study, the RADIUS study, and the Helsinki Ultrasound Trial) have been published that report varying sensitivities for ultrasound detection of fetal anomalies ranging from 35% to 56% [1820]. The Eurofetus study, a large multi‐center prospective trial of 3685 fetuses with structural malformations, deformations and dysplasias, reported a sensitivity of 61.4% (CI 95%, 59.8–63.0%) for routine ultrasound examination. Limited to major fetal anomalies, the sensitivity increased to 73.7% with higher rates for CNS (88.3%) and urinary tract (84.8%) abnormalities. The Helsinki Study group noted prenatal detection incurred a lower perinatal mortality rate, while the RADIUS study group’s findings did not. The difference in perinatal mortality rate between the two studies may be a reflection of their respective study designs (the RADIUS study group examined a low‐risk population and the Helsinki trial was population‐based), or the rate of termination between the two countries.

Prenatal ultrasound imaging has been thought to be suboptimal in the detection of fetal anomalies in the presence of oligohydramnios or maternal obesity. Few studies have specifically looked at the effect of low amniotic fluid volume on the detection of fetal anomalies. A study of 345 pregnancies ranging from 16 to 38 weeks affected by premature rupture of membranes (175 with oligohydramnios, 170 without oligohydramnios) showed no difference in detection of major fetal anomalies with rates of 7.4% and 10%, respectively [21]. With respect to maternal obesity, one retrospective cohort study of 11 135 singleton pregnancies at a single institution reported lower detection rates of congenital anomalies on both standard and targeted ultrasounds as maternal body mass index (BMI) increased. Detection rates for normal BMI, overweight, Class I, II, and III obesity were reported as 66%, 49%, 48%, 42%, and 25%, respectively [22].

The role of additional imaging modalities for detection of fetal anomalies, such as 3D ultrasound imaging and magnetic resonance imaging (MRI) remains adjunctive. For specific situations or anomalies, there may be a role in using additional modalities for prenatal counseling and postnatal therapy. Fetal MRI has been in use since 1983 and gained more traction in the 1990s after technical advancements improved accuracy with ultrafast T2‐weighted sequences. A systematic review of the literature in 2014 analyzed the additional value added by fetal MRI to CNS abnormalities detected by ultrasound. The review found that fetal MRI results confirmed ultrasound‐detected CNS abnormalities in 65.4% of fetuses and reported pooled sensitivity and specificity of MRI was 97% (95% CI, 95–98%) and 70% (95% CI, 58–81%) [23]. Strikingly, this review found that fetal MRI results differed from ultrasound in 30.2% and thereby significantly altered counseling and pregnancy management. To date, there has been one prospective blinded case–control study comparing the sensitivity and specificity of 2D ultrasound, 3D ultrasound and MRI in detection of fetal anomalies. Goncalves et al. reported fetal MRI, 2D ultrasound, and 3D ultrasound had similar sensitivities (80%, 78%, and 76% respectively) for overall detection of congenital anomalies [24]. For detection of CNS anomalies, fetal MRI was found to be statistically significantly more sensitive than 3D ultrasound but similar to 2D ultrasound. In 22.2% of cases, fetal MRI was found to provide additional information over ultrasound that affected prognosis, counseling, and or management.

Fetal echocardiography is widely used to aid in the prenatal detection of cardiac anomalies. To date, there are no evidence based appropriate use criteria that have been developed for referral of women for fetal echocardiography. A single center retrospective study in 2014 revealed that reported that suspicion of congenital heart disease on screening ultrasound was most predictive of positive echocardiogram findings (59.9% prevalence, 85% CI, 56.7–63.1%) [25]. A high prevalence of congenital heart disease was also seen in fetuses with a known chromosome abnormality (42.4% prevalence, 95% CI, 25.6–59.3%), incomplete screening exam (33.3% prevalence, 95% CI, 14.5–52.2%), known twin‐to‐twin transfusion syndrome (28.6% prevalence, 95% CI, 4.9–52.2%), and extracardiac anomalies on screening ultrasound (21.2% prevalence, 95% CI, 15.6–26.9%). The prevalence of congenital heart disease was also found to be increased if the patient was referred for more than one indication, ranging from 26% for one indication to 53% for three indications.

Fetal surgery

Prenatal intervention with fetal surgery has been a possibility in select cases of major anomalies for over two decades at highly specialized centers with the goal of improving outcomes. Fetal surgery can be performed via open hysterotomy or minimally invasive techniques (fetoscopy) for a narrow set of indications involving anomalies such as neural tube defects, fetal lung lesions, congenital diaphragmatic hernia, skeletal dysplasias, sacrococcygeal teratomas, and obstructive uropathy. The literature has been largely limited to case series and cohort studies. One randomized controlled trial (Management of Myelomeningocele Study, also known as MOMS) compared prenatal and postnatal repair of myelomeningocele with hindbrain herniation and showed a clear survival benefit for fetal surgery before 26 weeks compared with postnatal repair for eligible cases and the trial was stopped for efficacy [26]. Prenatal surgery in this trial was shown to improve rates of fetal death, neonatal death and need for placement of cerebrospinal fluid shunt in first 12 months of life (68% versus 98%, relative risk, 0.70; 97.7% confidence interval [CI], 0.58–0.84; P < 0.001). Fetal lung lesions, such as congenital cystic adenomatoid malformation or bronchopulmonary sequestration) have been managed both prenatally and postnatally based on the presence of hydrops and gestational age at discovery. Two case series have noted that for those fetuses with hydrops and polyhydramnios less than 32 weeks gestation, fetal surgery, and thoracoamniotic shunting appears to improve survival [27, 28]. Management of fetal sacrococcygeal teratoma with prenatal surgery has also been reported in case series and found to be successful in the presence of co‐occurring hydrops, with reported survival rates of 30% and 55% for minimally invasive and open techniques [29, 30].

Delivery mode and timing

In the majority of cases, mode of delivery is not affected by the presence of a congenital anomaly and most affected pregnancies will, similarly, not require a preterm or early term delivery. However, it is reasonable to assume that cesarean delivery should be considered if the anomaly results in cephalopelvic disproportion, causes fetal soft tissue trauma during vaginal delivery, or the malformation affects the ability to assess fetal wellbeing in labor [31]. Four retrospective studies have been conducted that compare mode of delivery for meningomyelocele and no significant differences were found in short‐term neonatal outcomes in those delivered via vaginal or abdominal routes [3235]. There is no evidence that cesarean delivery is beneficial for fetuses with ventral wall defects, such as omphalocele. The data has been mixed with respect to outcomes for fetuses affected by gastroschisis; however, there is a large amount of confounding bias given studies that have been conducted are largely retrospective. In the last decade, six retrospective studies have been published that show no added benefit of cesarean delivery over vaginal delivery for fetal gastroschisis [3640]. In cases of cystic hygroma, cesarean delivery may be optimal for management of large anterior lymphangiomas obstructing the airway, though there are no data to support this recommendation. In the event that an EXIT (ex utero intrapartum therapy) procedure is indicated for successful delivery and intubation of a neonate with a lung mass causing airway compromise, cesarean delivery is necessary and is often a planned preterm delivery [41, 42

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Jul 20, 2020 | Posted by in GYNECOLOGY | Comments Off on 46: Fetal anomalies
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