Prenatal diagnosis of fetal defects and its implications on the delivery mode

4.1 Fetal CHDs

CHDs are the most common fetal structural anomalies, with the incidence ranging between 8 and 12 per 1,000 live births depending on the time of diagnosis [11]. The incidence of CHDs in early gestation can be even higher, given that some CHDs are complex and usually lead to fetal demise [12]. A growing number of CHDs are diagnosed in utero with improvements in ultrasonographic technology and an increase in the demand for prenatal screening. Up to 50–60% of CHDs require surgical corrections, and 25% of conditions from this group are critical, constituting a leading cause of infant mortality [12]. Due to prompt detection of a severe CHD that requires intervention shortly after delivery, planned intervention can take place at a tertiary center with a congenital cardiac surgery program implemented and units equipped to treat such cases, or at a hospital located within the proximity of such a center. Pregnancies with prenatally and postnatally diagnosed severe CHDs requiring neonatal surgical intervention differed significantly in terms of perinatal management and delivery planning [13]. Although the complexity of CHDs found in the prenatally and postnatally diagnosed groups was similar, neonates from the former group were born earlier and with lower birth weights than those diagnosed postnatally [13]. With the prenatal diagnosis, there is an opportunity to schedule the delivery at a tertiary center capable of offering a necessary cardiac intervention following a prompt evaluation by a multidisciplinary team of cardiology, surgery, intensive care, and neonatology specialists. Thus, the delivery location for pregnant women with a prenatal diagnosis of a CHD posing the risk of postnatal compromise should be planned appropriately. It was proved that prenatal diagnosis of CHDs was associated with lower birth weight, preterm delivery, and increased risk of primary cesarean delivery [14].

There is evidence that pregnancies with fetal CHD were significantly more often delivered by cesarean section due to non-reassuring fetal heart rate regardless of prenatal diagnosis of the anomaly [15]. Moreover, cases of neonates with CHDs have a greater tendency toward an unfavorable outcome (e.g., 5 min Apgar score < 7, seizures, and hypoxic-ischemic encephalopathy) independently of prenatal diagnosis of CHDs [15]. Additionally, according to the published evidence, the overall neonatal conditions and surgical outcome are better when the delivery occurs in close proximity of a cardiac center capable of providing surgical interventions for neonates with major CHDs [16]. However, there is still no consensus considering the optimal mode of delivery in pregnancies with fetal CHDs. The risk of maternal and fetal comorbidities was increased, regardless the type of cesarean delivery: elective or intrapartum. The severity of CHDs did not seem to change either the delivery route or immediate neonatal outcomes; the paramount importance in determining the mode of delivery in pregnancies with fetal CHDs was identification of preexisting obstetrical comorbidities [17]. Vaginal delivery was successful in 66.1% of cases of fetal cardiac anomalies [11]. Planned cesarean delivery in pregnancies with prenatally diagnosed fetal cardiac anomalies was more common than in pregnancies in which such anomalies were detected postnatally. Importantly, the planned cesarean delivery did not reduce the risk of composite neonatal morbidity compared with attempted vaginal delivery [11].

Neonatal outcomes of fetuses with CHDs can be improved by delaying elective delivery to at least 39 weeks; however, waiting beyond 42 weeks turned out to have a negative impact on their condition [18]. These findings are in contrast to the results of some recent studies that identified a small albeit significant negative trend in gestational age at delivery in infants diagnosed prenatally with single-ventricle defects [16]. After excluding elective cesarean deliveries, operative vaginal deliveries due to non-reassuring fetal heart rates were more common among CHD patients [19]. Moreover, neonates diagnosed prenatally with CHD were more often small for gestational age, had meconium-stained amniotic fluid, 1 and 5 min Apgar scores ≤ 7, non-reassuring fetal heart rate, and chorioamnionitis [19]. Physicians should be aware of these findings and consider them when deciding on the mode of delivery. Also, good communication between obstetrical and cardiological units is essential in this setting because elective labor induction before 39 weeks of gestation is not recommended for fetuses with CHDs unless patient-specific obstetrical or logistic issues or fetus-specific concerns about well-being exist [13]. The decision to terminate pregnancy in cases of severe anomalies or to refrain from intervention in favor of palliative care at birth is a complex and highly individualized process. Complex counseling should provide parents with all necessary support regardless of their choice. They should refrain from presenting their personal opinions during the discussion and focus on providing families with all the support essential to arrive at a decision. Informed consent should be driven by evidence and patient’s education. The purpose of informed consent is to enable the patient to make an informed decision.

4.2 NTDs

NTDs are complex and heterogenous groups of the congenital central nervous system (CNS) anomalies resulting from the failure of the neural tube to close [20]. This group includes several anomalies, e.g., anencephaly, spina bifida, and encephalocele. The incidence of NTDs has been reported at 0.89–0.93 per 1,000 live births in Europe, 0.53 per 1,000 in the United States, 0.2–9.6 per 1,000 in Latin America, and 0.62–13.8 per 1,000 in Arab countries [21]. Risk factors for NTDs include maternal folate deficiency, obesity, diabetes mellitus, fungus contaminants of maize, mycotoxins, heat, exposure to teratogens (valproic acid, carbamazepine, lead), influenza virus, and socioeconomic status [22].

Anencephaly is a severe pathology of neuroaxis development arising 26–28 days after conception due to impaired closing of the neural tube developing forebrain and variable amounts of brainstem being fully exposed [23]. Although some fetuses are born alive, anencephaly is recognized as a lethal condition with no possibility of effective treatment [24]. The global prevalence of anencephaly is estimated to be 5.1 per 10 000 births; in addition in countries where termination of pregnancy is prohibited, the incidence of anencephaly tends to be even higher [25,26]. Prenatal detection of anencephaly is possible during the first trimester ultrasound scan and it is considered reliable, and less than 25% of anencephaly is detected by ultrasound prior to 18 weeks of gestation [27]. During the first trimester, an early fetal anatomy assessment can detect not only structural non-genetic malformation but also anomalies associated with genetic defects different from the common chromosomal aberrations [28]. According to many authors, pregnancy with anencephaly should be terminated via the vaginal route, although induced labor may increase the risk of cesarean delivery [29]. There is also some evidence that compared with labor of spontaneous onset, elective labor induction in nulliparous women is associated with significantly more operative deliveries. Moreover, the difference in the delivery mode could be attributed to the gestation age and the risk of cervical damage by the bony basal skull of the fetus [29]. Additionally, the incidence of shoulder dystocia may increase due to a smaller head circumference (HC) in anencephalic fetuses, which enables full dilatation of the cervix and increases the risk of the shoulders getting stuck [30]. Another important problem is dysfunction of the hypothalamic-pituitary axis in anencephalic pregnancies, which leads to prolonged gestation that increases the risk of repeated cesarean delivery in women with a previous uterine scar [31].

Another example of NTDs is myelomeningocele. A large body of evidence shows that this anomaly can be successfully treated surgically during the prenatal period. The Management of Myelomeningocele Study demonstrated that morbidity associated with spina bifida can be reduced by fetal myelomeningocele closure via open maternal-fetal surgery. The documented beneficial effects of the treatment included the reduced need for ventriculoperitoneal shunting in the first year of life, reversal of hindbrain herniation, and improvement of motor function and neurodevelopmental outcomes at 30 months of age [32]. Open maternal-fetal surgery is performed via hysterotomy in the contractile portion of the uterus, similar to that created during a classical cesarean delivery. Since conventional hysterotomy is associated with a 4–9% risk of uterine rupture and a resultant increase in maternal and neonatal morbidity, the risk in pregnancy following open surgery can be similar or even greater [33]. A number of recently conducted studies demonstrated the effectiveness and safety of endoscopic treatments for NTDs. Compared with an open approach, fetoscopic repair of open NTDs was shown to reduce the incidence of cesarean delivery, preterm delivery, and other important complications, such as uterine scar dehiscence, with no significant difference in total costs of care from surgery to infant discharge [34]. During preoperative counseling, patients considering maternal-fetal surgery for myelomeningocele closure should be informed not only about the benefits in terms of the reduction of morbidity for the neonate and child but also about the associated maternal risks for the index pregnancy, as well as about the potential additive risk of uterine scar complications in future pregnancies. All those risks should also be considered during the management of subsequent pregnancy; thus, women with a history of maternal-fetal surgery for myelomeningocele closure in previous pregnancies should optimally be offered delivery at 36–37 weeks of gestation and be managed in close collaboration with a center having adequate expertise in fetal surgery [33]. Moreover, the decision on the mode of delivery should be based on prenatal diagnosis and the type of fetal therapy. If both open and endoscopic approaches are available at the perinatal center, both should be discussed because the later decision on the mode of delivery is also based on the fetal therapy used previously [34]. In the case of large anomalies with concomitant hydrocephalus, cesarean delivery is a highly recommended option. However, in the case of fetuses whose prognosis is grave based on the lesion level and size or in utero movement, vaginal delivery may be a preferable option. The results of a large meta-analysis suggest that routine cesarean delivery for fetuses with open NTDs does not necessarily improve neurological outcomes; however, it needs to be emphasized that available evidence on this matter is limited to small observational studies [35].

4.3 Gastroschisis

Gastroschisis is an abnormality of the abdominal wall that results in the herniation of the bowel and other abdominal organs, typically on the right side of normal umbilical cord insertion. Thanks to the progress in ultrasound technology, the majority of gastroschisis cases, approximately 90–98%, can be identified prenatally nowadays. The prevalence of gastroschisis has been estimated to be 0.5–1 per 10,000 births [36]. However, recent evidence suggests that the prevalence of gastroschisis is increasing, up to 5.1 per 10,000 births [36]. While the overall fetal-neonatal mortality due to gastroschisis remains relatively low (5–10%), pregnancies complicated by this anomaly are often associated with fetal growth restriction, preterm delivery, and neonatal complications, such as bowel atresia, perforation, stricture, ischemia, and necrotizing enterocolitis [37]. Risk factors for gastroschisis include young maternal age, tobacco and illicit drug use, low socioeconomic status, low body mass index, and infections [38]. The intestinal wall undergoes changes with the severity of inflammation, as shown histologically in both human studies and experimental animal models. The inflammatory changes may be mediated by exposure to amniotic fluid constituents. In 17% of the fetuses with gastroschisis, the exposed bowel coexists with other defects, such as intestinal atresia, necrosis, perforation, or volvulus, which is referred to as complex gastroschisis. The risk of morbidity and mortality in such patients is higher than in neonates with simple gastroschisis without concomitant intestinal defects [39]. The optimal timing and mode of delivery in pregnancies with gastroschisis are still a matter of debate. Some authors recommend elective preterm delivery to minimize the exposure of the gastrointestinal tract to the proinflammatory constituents of the amniotic fluid. Published evidence suggests that the induction of labor at 37 weeks of gestation was associated with lower rates of sepsis, bowel damage, and neonatal death compared with pregnancies managed expectantly beyond 37 weeks [40]. However, no difference in the outcomes of pregnancies terminated by elective delivery at 36 weeks and those treated expectantly until spontaneous labor was demonstrated in one randomized controlled trial [37]. Also, an optimal delivery mode in pregnancies complicated by gastroschisis raises some controversies. According to the literature, gastroschisis does not constitute an indication for routine cesarean delivery, and the decision on the mode of delivery should be based primarily on obstetrical conditions and the clinician’s and parents’ discretion [41,42]. There are centers that do not perform cesarean deliveries routinely in pregnancies with gastroschisis managed at their center, and the time of delivery for neonates with this anomaly is not arbitrarily controlled. However, as stated by some authors, neonates with gastroschisis delivered during nighttime received delayed closure more frequently [43]. Thus, scheduling the delivery in the morning hours, when all necessary specialists are available at the clinic, seems to be a reasonable option. According to many authors, the outcomes of vaginal deliveries and cesarean deliveries in pregnancies with gastroschisis are essentially the same; hence, this anomaly should not be considered an indication for elective cesarean delivery. Considering that cesarean delivery is known to be associated with increased maternal morbidity and lack of neonatal benefit, scheduled cesarean delivery in pregnancies with gastroschisis should not be recommended.

4.4 Fetal tumors

The estimated prevalence of all congenital tumors varies between 1 and 13.5 per 100,000 live births, and the true number of these anomalies may be higher as such conditions are likely not reported [44]. Detection of a fetal tumor constitutes a diagnostic and therapeutic dilemma given the variety of possible differential diagnoses and the variable course during the pregnancy and after birth [45]. The most challenging problem faced by a physician is the decision of whether a given case is eligible for ultrasonographic monitoring with a surgical intervention postponed postnatally. Frequently, it is impossible to distinguish between the fetal masses that require a prenatal intervention and those cases where immediate postnatal treatment is also an option [46]. Many fetal tumors are often found incidentally during the second- or third-trimester ultrasound examination [47].

It is estimated that fetal intracranial tumors account for 0.5–1.9% of all tumors detected in children [48]. Teratoma is the most commonly occurring brain tumor during fetal development, while astrocytoma, craniopharyngioma, and primitive neuroectodermal tumor are less common [48]. These tumors are typically detected during the third-trimester ultrasound scan. Unfortunately, fetal intracranial tumors often have a poor prognosis and can cause complications such as intracranial bleeding or dystocia during delivery [49]. The most common life-threatening fetal masses of the head and neck include vascular lesions, such as lymphangioma and hemangioma; these two types of lesions are often considered congenital malformations rather than true neoplasms [50].

Teratomas are neoplasms containing the derivatives of all three germ layers, usually, they are benign and very seldom undergo malignant transformation. Oropharyngeal teratoma, also referred to as an epignathus, constitutes 2–3% of all congenital teratomas. Cervical teratomas are usually detected as large masses that may extend in all directions. They may contribute to a significant hyperextension of the fetal neck, which may result in dystocia. The prognosis in fetal teratoma depends on the size and location of the mass and the consequent risk of airway obstruction [51]. Lymphatic malformations of the fetal head and neck are benign lesions very often found as fluid-filled, multiseptate cysts. They typically arise in the anterior or posterior triangles of the neck, and sometimes if venous components are present, they contain phleboliths – focal calcifications. Lymphatic malformations may be the cause of a lethal airway obstruction that requires intubation promptly after delivery and may lead to infection if left untreated. Optimal treatment of prenatally diagnosed teratomas and lymphatic malformations typically involves surgical excision, and the prognosis after treatment is usually very good [52].

The incidence of sacrococcygeal teratoma is estimated to be 1 in 40,000 live births, and it is more commonly diagnosed in female infants [53]. Typically, sacrococcygeal teratomas are present as an exophytic mass located in the sacrococcygeal area. Depending on the location of the mass relative to the body, four types are distinguished: type I is external, type II is equally located both externally and internally, type III is mainly internal, and type IV is entirely internal [54]. The presence of a sacrococcygeal teratoma may increase perinatal morbidity and mortality due to dystocia, fetal hydrops, polyhydramnios, bleeding, or cardiovascular complications [55]. Prognosis related to vascular complications caused by the tumor can be determined based on the serial evaluation of the heart size and Doppler measures of the fetal cardiac output [56]. Doppler interrogation of the umbilical arterial flow showing diminished or reversed diastolic flow reflecting competitive “steal” from the placenta to the sacrococcygeal teratoma is a marker of poor outcome [57]. Mirror syndrome is a life-threatening condition associated with maternal fluid retention and hemodilution; the syndrome occurs concomitantly to fetal hydrops and manifests as progressive maternal edema “mirroring” that of the affected fetus [58]. The treatment of sacrococcygeal teratomas involves surgical removal of the tumor mass using either open surgery or laparoscopic closure of the vessels supplying the tumor. The delivery method for fetuses with this condition depends on several factors, including the size of the tumor and the fetal condition. Vaginal delivery may still be an option for fetuses with an uncomplicated tumor < 5 cm in diameter; otherwise, cesarean delivery is the preferred method [59].

4.5 Microcephaly

Microcephaly, which is defined as an HC that is smaller than 3 SD below the mean for a person’s age and sex, is a neurological marker, which can be detected antenatally during a routine ultrasonographic examination or post-partum during the neonatal physical examination. Microcephaly is a relatively rare condition, with an estimated prevalence of 0.1–0.5% [60]. The diagnosis of microcephaly can be challenging, given a plethora of available cut-off values. The prognosis varies depending on the severity of microcephaly, its etiology, and accompanying manifestations [60]. HC below 3 SD of the mean is more likely to be associated with various disorders, whether genetic or non-genetic, that affect the development of the brain and contribute to intellectual disability and neurological abnormalities [60]. Abnormal pelvic proportions or fetal head dimensions that are too small or too large can lead to prolonged or arrested labor and may increase the risk of instrumental delivery and maternal and fetal complications [61]. Increased biparietal diameter in a term fetus at up to 7 days before labor was found to be associated with a significantly higher rate of operative vaginal deliveries without adverse neonatal outcomes [60]. Large HC was shown to be an independent risk factor for operative vaginal delivery and unplanned cesarean delivery; maternal and fetal issues should be considered, including primiparity or multiparity [62]. The mode of delivery and perinatal outcomes in fetuses with isolated microcephaly are similar to those in those with a normal HC. Further prospective studies based on valuable pre-labor and ultrasonographic data are needed to understand better the effect of microcephaly on labor progress and perinatal factors.

4.6 Lung and thorax malformations

CCAM of the lung is a rare defect of the terminal bronchioles. CCAM occurs due to an alteration in embryogenesis between the fifth and seventh week of gestation [63]. The overall prevalence of CCAM remains unknown, partly due to the non-universal nature of prenatal ultrasound screening and partly because of the variety of diagnostic classifications and criteria. The reported prevalence varies between 1:25,000 and 1:35,000 live births [64]. Prenatal diagnosis can be established with ultrasonographic techniques. If a fetal thoracic mass is detected in ultrasound, CCAM should be considered as a differential diagnosis, along with CDH, bronchopulmonary sequestration, and other, much less frequently observed, anomalies such as bronchogenic or enteric cysts, neuroblastoma, cerebral heterotopia, congenital lobar emphysema, mediastinal cystic hygroma, and unilateral bronchial atresia [64]. Macrocystic CCAM can mimic CDH with herniated stomach and intestines. Bronchopulmonary sequestration, with an ultrasonographic presentation of a well-defined homogenous mass, is characterized by the presence of an aberrant nutrient artery, absent in the case of CCAM. The prognosis varies with some anomalies undergoing spontaneous intrauterine resolution without observable pathologies found after birth. The large CCAM can interfere with the cardiovascular function of the fetus, changing loading conditions due to cardiac compression and the creation of tamponade-like physiology. Progressive changes, corresponding to alterations in ventricular filling and compliance, can be identified on serial fetal echocardiography with Doppler interrogation. In some cases, those abnormalities may lead to mortality due to pulmonary hypoplasia or moderate respiratory symptoms during childhood, and some persistent lesions can cause recurrent infections and even undergo malignant transformation [65]. Thus, surgery is usually necessary after birth. A large CCAM with early signs of hydrops is a fatal condition, and fetal surgical intervention should be considered as rescue therapy in such cases.

CDH is a congenital birth defect that occurs in approximately 1 in 3,000 live births [66]. The main determinants of short-term prognosis in such cases are persistent pulmonary hypertension of the newborn and the degree of pulmonary hypoplasia. Preterm delivery in CDH fetuses is associated with poor outcomes, with survival rates of 35–43% for newborns delivered before 37 + 0 weeks gestation [67]. CDH can be managed prenatally through the laparoscopic percutaneous endoscopic tracheal occlusion. Deployment of an occlusive balloon within the fetal trachea may promote lung growth and improve neonatal outcomes [68]. Unfortunately, such therapy is associated with an increased rate of preterm delivery. Published evidence shows that the mode of delivery in pregnancies with CDH (vaginal delivery vs cesarean delivery) is not associated with neonatal morbidity or mortality [68,69]. The survival rates in the case of planned cesarean delivery and vaginal delivery were shown to be similar; a lower survival rate was documented solely in the subgroup in which emergency cesarean delivery was conducted after an unsuccessful attempt at vaginal delivery [70]. Based on these findings, the mode of delivery in pregnancies with CHD should be chosen primarily based on obstetrical indications, as this anomaly alone does not constitute a sufficient reason for planned cesarean delivery. The tracheal balloon should be removed by ex utero intrapartum treatment (EXIT). The EXIT procedure is an established method to secure obstructed neonatal airways during delivery while still maintaining fetoplacental circulation for 20–30 min or more [71]. To be performed successfully, the EXIT procedure requires coordination and collaboration among physicians of maternal-fetal medicine, neonatological intensive care, obstetrical and pediatric anesthesiology, interventional radiology, and pediatric otolaryngology–head and neck surgery, as well as two teams of surgical nurses.