Cesarean Delivery in Fetal Triploidy: Clinical Considerations and Case Study Insights

Introduction

Fetal triploidy is a lethal chromosomal abnormality that arises from the presence of 3 sets of chromosomes instead of 2, resulting in an abnormal number of total chromosomes per cell (69, XXX; 69, XXY; or 69, XYY) [1]. It is estimated that 1–3% of all conceptions are triploid [2], and up to 20% of first-trimester spontaneous miscarriages are triploid. At 16 weeks, the incidence of triploidy is 1: 30 000, and at 20 weeks, it drops to 1: 25 0000 because of spontaneous pregnancy loss [3]. In addition to multiple structural anomalies, triploidy can be associated with placental hydatid disorder, fetal growth restriction, and even preeclampsia [3,4].

Current standard pregnancy management includes early aneuploid screening. Fetal triploidy, however, is not one of the aneuploid conditions screened for by 2 of the most commonly employed tests, the first-trimester screening (FTS) or the noninvasive prenatal testing (NIPT) [5,6]. Consequently, waiting until the detection of a spectrum of fetal abnormalities consistent with triploidy on ultrasound is the rule [7].

Invasive testing is required to make a definitive diagnosis, and genetic counseling is crucial in discussions of the options pregnant women have to choose a definitive fetal chromosomal test [8]. We present a case of fetal triploidy in a pregnant 17-year-old woman who had inconsistent prenatal care and an abnormal fetal ultrasound before 20 weeks. She presented at our facility at 33 weeks’ gestation with multiple congenital anomalies on ultrasound. She had declined invasive testing for fetal karyotype, which resulted in a counseling dilemma regarding her choice of delivery methods.

Case Report

A 17-year-old Brazilian woman, primigravida, was seen at 10 weeks’ gestation confirmed by vaginal ultrasound. During her first visit at her prenatal clinic at 10 weeks, she was screened and found negative for trisomies 21, 13, and 18, as well as monosomy X, triple X, and certain microdeletions, using the NIPT, a noninvasive prenatal assay that uses cell-free fetal DNA (cffDNA). She also had a normal nuchal translucency measurement at the time of her scan. She returned to her prenatal clinic at 15 weeks and had a maternal serum alpha-fetoprotein to help screen for open neural tube defect, and the test was negative. She returned for an ultrasound at 19 weeks, and the fetus was already growth-restricted. At that scan there was a ‘concern for a fetal heart defect’ on the ultrasound. If she received counseling after her 19-week ultrasound, it was not documented. She did not receive prenatal care until she presented to our prenatal center at 33 weeks’ gestation.

When she presented here at 33 weeks, she had complaints of several weeks of intermittent, unprovoked, unexplained lower abdominal pain and nausea. She reported normal fetal movements and no trauma or vaginal bleeding. Her physical examination revealed a fundal height of 24 weeks, cervix closed, 50% effaced, and -3 station. An extended fetal monitor strip was reassuring, with no decelerations, moderate variability, and reactivity without contractions. The rest of her physical exam was normal, and the reason for her pain was not apparent. An abdominal ultrasound indicated a severely growth-restricted fetus with multiple fetal anomalies, including a fetal heart with a ventricular septal defect, an overriding aorta, and presumed tetralogy of Fallot (Figures 1, 2), a partially absent cavum septum pellucidum, upper extremities with fixed wrist flexion, and intrauterine growth restriction. She was seen by pediatric cardiology, genetic counseling, and the neonatal group. She was counseled and offered amniocentesis for fetal karyotyping at 33 weeks, but she declined. Between 33 and 37 weeks, she was seen in the obstetric clinic weekly and had standard antepartum surveillance. Because of the fetal growth restriction and absent end-diastolic velocity on the umbilical artery Doppler, the neonatal team was informed, and a cervical ripening and labor induction was begun at 37 weeks. She was counseled extensively about the likely prognosis of the infant and consented to a cesarean for fetal indications despite the anomalies. After 25 µg of misoprostol was placed vaginally, persistent nonreassuring fetal surveillance was noted, and an emergency low transverse cesarean delivery was performed. The female infant weighed 1.365 kg with Apgar scores of 6 and 9 at 1 and 5 minutes after delivery.

The newborn required intubation and transitioned to high-flow jet ventilation and required continuing escalation of respiratory support. The infant was noted to have pulmonary hypoplasia, multiple congenital heart defects, and concern for septo-optic dysplasia. Consequently, no medical intervention was available to improve or cure the infant’s condition. At 15 days of life, she was diagnosed with triploidy (69XXX) with no evidence of mosaicism. After extensive counseling with genetics and palliative care, the parents opted for redirection of care to palliation. At 20 days of life, the patient’s infant died while in the hospital. The patient was discharged 3 days postoperatively after receiving a 68 mg etonogestrel implant for contraception.

Discussion

Triploidy occurs from a complete extra set of chromosomes from the normal of 46 to the triploid of 69, established at conception [8,9]. It occurs either when 1 normal sperm fertilizes an egg that has an extra set of chromosomes or if 2 sperm fertilize a normal egg [9]. There are 2 types of true triploidy, defined by the extra chromosomes’ origin. The additional set of chromosomes in type I is diandric or paternal in origin. In these cases, the placenta is typically enlarged, there are elevated levels of maternal serum beta human chorionic gonadotropin, and there is increased nuchal translucency in the first trimester ultrasound. In type II triploidy, the additional set of chromosomes is digynic or maternal in origin. This is the most common form of triploidy, making up 72% of the fetuses that survive past 14 weeks [2]. Digynic triploid pregnancy is characterized by a small placenta and asymmetrical fetal growth restriction [4]. It is rare for triploidy pregnancies to continue to reach term since they most often result in spontaneous abortion [3]. Triploid infants who are born alive have multiple anatomic anomalies, including limb anomalies, neural tube defects, cardiac abnormalities, and microcephaly, and have an extremely short lifespan unless they have a mosaic triploidy [4,10].

Some of the ultrasound characteristics of true triploidy include molar changes of the placenta, holoprosencephaly, exomphalos, and fetal nuchal translucency thickness above the 95th percentile [7]. There is no remedy for the condition, and all true triploid infants who survive the birth process die from the condition.

Early prenatal screening for chromosomal aneuploidy has become a standard of care in the United States. One of the many methods of maternal serum screening relies on cell-free fetal DNA (cffDNA), and all of these methods can be utilized as early as 10 weeks of gestation [7]. Fetal triploidy is not detected routinely, but cffDNA testing methodology that utilizes single nucleotide polymorphism (SNP)‐based NIPT will detect 11% of triploidies. Unfortunately, our patient’s plasma was not run with this method, but a technique that employs next-generation sequencing to identify common aneuploidies. The standard test of that center is to offer a NIPT that uses cffDNA at 10 weeks.

The patient’s fetal ultrasound at 19 weeks suggested ‘a concern for a heart problem’ based on the records we reviewed when she first presented to us at 33 weeks. No other details were supplied, but in general, a targeted fetal ultrasound interpreted by a trained imager is highly accurate and extremely useful in pregnancy management [8]. A referral for fetal echocardiography would be a likely follow-up choice for the fetal heart anomalies [11]. Abnormal findings on ultrasound may also suggest a need for a definitive fetal karyotype. An amniocentesis is an invasive test performed after 15 weeks of gestation that can provide a definitive fetal karyotype [12]. If the karyotype is normal, the delivery should be planned judiciously based on the spectrum of anomalies and the advice of pediatric subspecialists and counselors [13]. Unfortunately, the outcome of a triploid fetus will be unchanged regardless of the management.

The patient could also elect to terminate the pregnancy with or without a normal karyotype [14]. There are data that 40% of patients elect to continue the pregnancy despite facing a terminal condition of their fetus [15]. How the delivery is managed with a fetus that has a lethal anomaly is highly controversial and personal. A cesarean delivery for nonmaternal indications places the mother at risk, and the general consensus is that it should be performed for medical indications only [16].

However, this decision may be difficult for the patient and is ultimately between the patient and her caregiver. Information on the condition and options for the patient is supplied through trained counselors, whom most pregnant women endorse. The majority (78%) of women with normal fetuses who are offered genetic counseling agree to counseling, and the incidence is even higher if known fetal anomalies are present [17]. Regardless of the counseling content, however, our patient was managed per routine fetal monitoring protocol, which resulted in a cesarean delivery for fetal indications.

This case is notable because the lack of a definitive karyotype was injurious to the patient. It resulted in an unnecessary cesarean, which has immediate and long-term health consequences. Reproductive autonomy is a solid principle, and to decline an invasive fetal test is a fundamental patient right [18]. The care provider’s obligation is to inform the patient of the consequences of the choice, including potential effects on future childbearing.

This case can have legal implications. Should a cesarean delivery be offered if the outcome will be fatal? Trained and interested counselors are critical components in the management of these cases.

Conclusions

Triploidy is a unique chromosomal abnormality that is rarely seen at term. This case presented a unique scenario as the patient declined amniocentesis which could have been attempted any time after 15 weeks. In this case, the lack of definitive knowledge of the lethality of the fetal condition resulted in a cesarean delivery of an infant with projected severe life-ending anomalies. Screening for genetic conditions other than triploidy is routine and is performed early in pregnancy. Targeted second-trimester ultrasound is also not diagnostic for triploidy but highly reliable for detecting isolated or multiple fetal anomalies. An amniocentesis after 15 weeks can provide a definitive fetal karyotype, which, in many cases, is information that will help the patient make essential choices about her care. Access to trusted counseling is critical. Avoiding an operative delivery for a fetus with a lethal anomaly is our recommendation. The dilemma this case provokes is how to manage a fetus with a likely but unconfirmed lethal condition, when a straightforward definitive test is available, knowing that the patient may incur unnecessary maternal reproductive consequences.