Trisomy 21 in one of extremely low birth weight twins

Abstract

Prematurity is frequently seen in the neonatal intensive care unit, and trisomy 21 is an often diagnosed neonatal disorder. We report a unique case of extremely premature twins, one of whom was ultimately diagnosed with trisomy 21. We were able to examine the neonatal courses and outcomes of these twins, which were similar despite the presence of trisomy 21 in one twin. This is the first report comparing the neonatal course of an infant with trisomy 21 to an unaffected twin in patients born so prematurely, and demonstrates the difficulty of making the diagnosis of trisomy 21 based solely on physical examination in premature infants.

1. Introduction

Trisomy 21 (Down syndrome) is the most frequent chromosomal disorder in live-born infants; the condition occurs in about 1 in 1,000 live births [1,2]. Infants with Down syndrome are often born prematurely [3], While physical examination findings which raise the suspicion for Down syndrome are usually quite apparent in older patients, the diagnosis can be challenging in the neonatal period, especially in premature infants [4]. In Down syndrome, the physical examination findings for which clinicians most commonly check are: hypotonia, upslanting palpebral fissures, single palmar creases, low-set ears, a wide gap between the first and second toes, and a fiat nasal bridge. Other physical examination findings seen in Down syndrome include epicanthal folds, downturned corners of the mouth, excess nuchal skin, brachycephaly (a wide, flattened head shape), Brushfield spots in the iris, a protruding tongue, brachydactyly (short, broad hands), and fifth finger clinodactyly (incurving) [5,6].

The literature on Down syndrome in infancy is robust, and there are numerous case reports of Down syndrome occurring in one of multiple gestations, but there is relatively little literature discussing neonatal outcomes in extremely low birth weight (ELBW) infants with Down syndrome [4,7–14]. The presence of Down syndrome in one of two ELBW twins provides an opportunity to compare the clinical outcomes of premature infants with and without this disorder.

Neonates with Down syndrome are prone to a variety of medical issues, including feeding difficulties, hearing loss, congenital heart disease, ophthalmologic problems, gastrointestinal atresias, hematologic abnormalities, and congenital hypothyroidism [1,15]. In addition to medical concerns related to Down syndrome, the care of ELBW (birth weight < 1000 g) infants may be complicated by respiratory distress syndrome, eventual bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, and susceptibility to infections [16,17]. The combination of ELBW and Down syndrome might be suspected to result in a much higher degree of morbidity than either of the two diagnoses alone.

2. Patients

The patients are former 26 and 2/7 week female twins born to a 20 year-old gravida 4 mother (previous pregnancies had resulted in the delivery of a term infant and an elective termination). The mother had had incomplete prenatal care and a history of at least weekly phencyclidine (PCP) use during pregnancy. She presented to a community hospital because of abdominal pain, and was found to be in active labor. Due to non-reassuring fetal heart tones, delivery was performed by emergent caesarean section. Placental pathology showed a dichorionic, diamnionic twin placenta. The patients’ characteristics and birth data are presented as Table 1.

Table 1.

Clinical details

	Twin A (no evidence of trisomy 21)	Twin B (trisomy 21)
Apgars (at 1 & 5 minutes)	8,9	8,8
Weight at birth	908 g (50th %)	512 g (< 3rd %, approximately 50th % for 22 weeks gestation)*
Length at birth	33 cm (10th–50th %)	29 cm(< 3rd %, approximately 50th % for 23 weeks gestation)*
Head circumference at birth	24 cm (10th–50th %	21 cm (< 3rd %, approximately 50th % for 23 weeks gestation)*
Placental weight	200 g	180 g
Days on ventilator	0	43
Age when full feeds achieved (d)	43	63
Age when transferred to rehabilitation hospital (d)	73	76
Weight on DOL 30	1430 g (10th–50th %)	1070 g (3rd–10th %)*
Weight on DOL 71	2750 g (50th %)	1750 g(< 3rd %)*

^*Growth centiles based on premature infants, not on infants with trisomy 21, as there are no standardized charts available for the growth of premature infants with trisomy 21.

DOL: day of life.

The infants were transferred to a neonatal intensive care unit (NICU) in a children’s hospital on their first day of life. The patients were initially critically ill, and were stabilized per routine NICU protocol. During Twin B’s 7th week of life (approximately 32 weeks corrected gestational age), the diagnosis of Down syndrome was suspected because of her dysmorphic facial features. Examination by a pediatric geneticist noted the presence of redundant nuchal skin, bilateral epicanthal folds, bitemporal narrowing, micrognathia, a prominent tongue, a single palmar crease on the left and an interrupted transverse palmar crease on the right, and short fifth middle phalanges bilaterally. Her tone was normal for gestational age, and her ears were not low-set. With the presence of a membranous ventricular septal defect (VSD), Twin B thus had at least 8 signs of Down syndrome. A chromosome analysis on peripheral blood confirmed trisomy 21. Twin A did not have Down syndrome. The following is a description of the infants’ clinical courses in the NICU, with emphasis placed on differences between the two patients.

2.1. Twin A (the twin without trisomy 21)

Twin A initially had respiratory distress requiring nasal continuous positive airway pressure (NCPAP) for 9 days, followed by high flow nasal cannula (NC) and regular nasal cannula for the rest of her stay in the NICU.

Twin A received parenteral nutrition for 23 days for 23 days. Trophic feeds were attempted on DOL 10, but were discontinued almost immediately due to bilious residuals. On DOL 35, feeds were again stopped for 20 days due to concern for necrotizing enterocolitis (NEC). She achieved full feeds on DOL 63 and by discharge was tolerating approximately 25% of her feeds orally and the rest by gavage.

Serial head ultrasounds on twin A showed a resolving grade I intraventricular hemorrhage (IVH). Her eye exams showed no retinopathy of prematurity. Hearing test at discharge was failed bilaterally. Twin A was discharged to a rehabilitation hospital at 73 days of life (corrected age 36 5/7 weeks).

2.2. Twin B (the twin with trisomy 21)

Due to respiratory distress, twin B was intubated and received mechanical ventilatory support shortly after delivery. She was extubated to high flow NC and then regular NC with a flow of 2L/minute with a FiO₂ of 0.25. A patent ductus arteriosus (PDA) requiring surgical ligation was noted on echocardiogram on DOL 4. A repeat echocardiogram on DOL 46 showed a moderate membranous ventricular septal defect, a small atrial septal defect, right-sided ventricular pressure overload, and a small left-to-right atrial shunt. She eventually required repeat cardiac surgery for ASD and VSD repair.

Twin B received total parenteral nutrition (TPN) exclusively until DOL 27. Trophic feeds were attempted on DOL 17 but were stopped for 10 days due to abdominal distention and subsequent radiographs suggesting NEC. She achieved full feeds via nasal gastric tube on DOL 43.

Serial head sonograms showed no IVH. Eye examination on the day of discharge showed stable ROP bilaterally (Stage 2, Zone 2). Hearing test at discharge was failed bilaterally. Twin B was discharged to a rehabilitation hospital at 76 days of life (corrected age 37 1/7 weeks).

3. Discussion

A comparison of the NICU course of these twins shows that the two had similar and relatively positive outcomes at the time of their transfer from the NICU to a rehabilitation facility despite extreme prematurity, ELBW, a history of maternal substance use, and the presence of trisomy 21 in one of the infants. Both patients were ready for transfer to a rehabilitation hospital within several days of each other. The main differences in clinical courses was that the twin with trisomy 21 required greater early ventilatory support, needed surgical intervention for correction of her congenital heart lesions, and was consistently smaller than the twin without trisomy 21.

There are several potentially confounding issues in this case. First, discordant growth is common in twin pregnancies, and the fact that Twin B was small for gestational age (SGA) may not be completely due to the presence of trisomy 21. However, the fact that twin B but not twin A was SGA could alone account for twin A’s relatively milder course in the NICU. Second, it is possible that other variables during their hospitalization could have resulted in the observed differences in their clinical courses.

Finally, this case highlights the difficulty of making diagnoses based on physical examination alone in the instance of extreme prematurity. In a report of another infant with trisomy 21 born at 26 weeks gestation, the diagnosis was suspected early because of a myeloproliferative disorder. However, only at 27 weeks of age (13 weeks corrected gestational age) were findings on physical examination concerning for Down syndrome [4]. Despite this challenge, it is important to conduct thorough physical examinations even in instances of prematurity and critical illness, and clinicians must be aware that they may need to rely on diagnostic clues other than the physical exam.