Received: 10 May 2020 Revised: 4 September 2020 Accepted: 19 October 2020

DOI: 10.1002/ajmg.a.61948

ORIGINAL ARTICLE

Neonatal complications of Down syndrome and factors

necessitating intensive care

Katelyn Seither1 | Sammy Tabbah2 | Dawit G. Tadesse3 | Kristen R. Suhrie1,4

1
Perinatal Institute, Division of Neonatology,
Cincinnati Children's Hospital Medical Center, Abstract
Cincinnati, Ohio Limited knowledge exists about how frequently newborns with Down syndrome
2
Division of Maternal-Fetal Medicine,
receive a prenatal diagnosis, require intensive care, and what surgical and medical
Department of Obstetrics and Gynecology,
University of Cincinnati, Cincinnati, Ohio factors are contributory. A retrospective cohort study was performed for patients
3
Division of Epidemiology and Biostatistics, with a diagnosis of Down syndrome born in 2013 and 2014 who sought care at
Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio Cincinnati Children's Hospital Medical Center during the first year of life. Data were
4
Department of Pediatrics, University of extracted from the electronic medical record through the first year of life including
Cincinnati, Cincinnati, Ohio
need for intensive care as a newborn, prenatal diagnosis, and medical and surgical
Correspondence complications. Of the 129 patients in the study, 65% required intensive care as new-
Kristen R. Suhrie, Perinatal Institute, Division
borns. The presence of a structural abnormality that required surgical correction in
of Neonatology, Cincinnati Children's Hospital
Medical Center, 3333 Burnet Ave, MLC 7009, the neonatal period and certain types of congenital heart disease not requiring surgi-
Cincinnati, OH 45229.
cal intervention in the neonatal period were positively associated with the need for
Email: kristen.suhrie@cchmc.org
intensive care. A minority of infants, 8%, had a confirmed prenatal diagnosis. A
majority of newborns with Down syndrome required intensive care following birth
while a minority had any concern for the diagnosis prenatally. Improving prenatal
diagnostic rates would allow for better prenatal counseling and delivery planning,
while targeting therapeutic interventions for this population is needed to improve
outcomes.

KEYWORDS

Down syndrome, intensive care, newborns, prenatal diagnosis

1 | I N T RO DU CT I O N a prenatal diagnosis in live born infants with Down syndrome or their

Down syndrome has an incidence of 1:700 live births in the United
States and is associated with many complications including congenital
heart disease (CHD), respiratory insufficiency, and gastrointestinal abnor-
malities (Bergstrom et al., 2016; Ergaz-Shaltiel et al., 2017; Mai
et al., 2019). Highly sensitive screening and diagnostic tests along with
guidelines for their use exist for the detection of a fetus with Down syn-
drome, allowing for comprehensive prenatal evaluation, counseling, and
delivery planning for affected families (ACOG, 2007a; ACOG, 2015;
Bianchi et al., 2014). While much has been published about prenatal rates
of Down syndrome detection with various screening test and termination
rates following a prenatal diagnosis, less is known about the incidence of
neonatal outcomes (de Graaf, Buckley, & Skotko, 2016; Hurford, Haw-
kins, Hudgins, & Taylor, 2013). A recent study from England estimated
that 46% of all neonates with Down syndrome are requiring intensive
care as neonates with prematurity being a significant contributing factor
(Mann et al., 2016). What is not yet understood is what medical and/or
surgical issues are driving this need for advanced care.
The objectives of this study were to evaluate a cohort of infants
with Down syndrome to determine rates of prenatal diagnosis, assess
the incidence of intensive care unit (ICU) admission during the new-
born period as well as medical and surgical complications associated
with the need for intensive care, and describe the burden of early
health complications experienced by this unique population.

Am J Med Genet. 2020;1–8. wileyonlinelibrary.com/journal/ajmga © 2020 Wiley Periodicals LLC 1

2 SEITHER ET AL.
2 | P A T I E NT S A N D M E TH O D S
A retrospective chart review was performed at Cincinnati Children's
Hospital Medical Center (CCHMC), which is a free-standing children's
hospital, that included all children with a diagnosis of Down syndrome
born between January 1, 2013 and December 31, 2014, who sought
care at our institution for any reason during the first year of life.
During the study period, CCHMC was the exclusive provider for ICU
care to newborns in the Cincinnati area and was the only provider of
pediatric sub-specialty care. The CCHMC neonatology division evalu-
ated 80% of all newborns not requiring ICU care during the study
period by providing inpatient newborn services at all the delivery
hospitals in the Cincinnati area. Services such as echocardiography
and genetic counseling were only available at CCHMC for pediatric
patients born during the study period in the Cincinnati region. One
hundred and thirty-five patients met inclusion criteria; six were subse-
quently excluded from analysis due to insufficient data in the elec-
tronic medical record, resulting in a final cohort of 129. Electronic
medical records were reviewed, and data were extracted until each
patient turned 1 year of age. Information regarding demographics,
prenatal diagnosis status, maternal age, gestational age, birth weight,
need for care in an ICU in the neonatal period, all diagnoses, and
surgical interventions were collected. All patients underwent echo-
cardiography on an inpatient or outpatient basis either at CCHMC or
their referring institution. Cardiac diagnoses were grouped into the
following categories: (I) Complex anomalies including Tetralogy of
Fallot, interrupted aortic arch, coarctation of the aorta, transposition
of the great arteries, and single-ventricle lesions; (II) Complete or
partial atrioventricular (AV) canal; (III) Isolated atrial septal defect
(ASD), ventricular septal defect (VSD), or patent ductus arteriosus
(PDA); (IV) Other CHD including valvular lesions, septal hypertrophy,
and vascular rings; (V) Pulmonary hypertension; (VI) Heart failure.
All data were stored in a secure REDCap database. Statistical
analysis was performed using the Fisher exact test or the binomial/
proportion test to compare categorical variables and the two-tailed
Student's t test to compare the means of two populations with
assumed unequal variance for the continuous variables. For all ana-
lyses, a p value of <.05 was considered statistically significant. All the
statistical tests were conducted using RStudio version 3.5.2 (2018).
This study was approved by the CCHMC Institutional Review Board
(Study Number 2015-9416) with waiver of parental consent.
3 | RESULTS
3.1 | Description of study cohort
Table 1 provides demographic data for the cohort as well as perinatal
characteristics sorted by need for ICU care in the neonatal period. Of
the 26 patients born preterm (<37 weeks gestation), the indication for
preterm birth could be determined for 22 of the 26 patients (85%).
There were maternal indications for delivery including pre-eclampsia,
preterm labor, and vasa previa in nine patients. An additional 12 patients
were delivered due to concern for fetal well-being with indications
including non-reassuring fetal heart tracing, abnormal umbilical artery
dopplers, severe growth restriction, and hydrops fetalis. One patient
was delivered emergently in the setting of placental abruption. The
average birth weight was 2,827 g across the cohort. Four patients in
the cohort (3%) died within the first year of life. The causes of death
for these patients were multifactorial and included respiratory failure,
pulmonary hypertensive crisis, cardiogenic shock, and sepsis with multi-
organ dysfunction. To understand if the study captured all children born
with Down syndrome within the eight-county primary service area for
CCHMC, we noted there were 51,396 total births in 2013 and 2014 in
those eight counties. Our study cohort identified 70 patients with
Down syndrome from the primary service area born in the years of
interest, which resulted in a calculated incidence of 1 in 734 live births;
this is comparable to the incidence of 1 in 700 live births reported in
the literature (Mai et al., 2019).
3.2 | Prenatal diagnosis rates and predictors of a
prenatal diagnosis
Table 2 defines the number of patients with a prenatal diagnosis of
Down syndrome and predictors of having a prenatal diagnosis. Prena-
tal diagnosis status was able to be extracted from the infant's chart
for a majority (88%) of patients in the cohort. A confirmed diagnosis
was defined as an abnormal karyotype obtained via amniocentesis or
chorionic villus sampling, while a suspected diagnosis was defined as
any of the following abnormal screening test: cell-free DNA, second
trimester quad screening, and/or characteristic ultrasound findings. All
patients in the cohort had a prenatal/postnatal karyotype or micro-
array confirming the diagnosis of Trisomy 21; one patient was found
to be mosaic for the condition with 85% mosaicism.
3.3 | Incidence and predictors of ICU care
Table 1 defines the number of patients needing ICU care in the neonatal
period as well as demographic and perinatal characteristics associated
with the need for advanced care. The mean length of stay for those
needing ICU care was 29 days (range 1–134 days; median 20 days).
Infants with Down syndrome required ICU care for a variety of reasons.
While the indication for ICU admission was multifactorial for all
patients, we defined the medical and surgical complications and deter-
mined which problems predicted the need for ICU care. The neonatal
noncardiac diagnoses for the cohort were described by systems in
Table 3, and the incidence of each problem was compared between
those requiring ICU care versus not. Table 3 describes the non-cardiac
medical diagnoses for those patients who required ICU care as new-
borns. Given the high incidence of respiratory problems in the cohort
and the known complication of sleep disordered breathing in Down
syndrome patients, each EMR was reviewed to determine if poly-
somnography was performed and the results were documented.
Twenty-nine patients had a polysomnogram performed during the
SEITHER ET AL. 3

T A B L E 1 Demographics and
ICU admission
perinatal characteristics by ICU
admission status Yes No Total

n (%) n (%) n (%) p 95% CI

Study cohort 84 (65) 45 (35) 129(100)
Sex .27 (0.69,3.35)
Male 46 (70) 20 (30) 66 (51)
Female 38 (60) 25 (40) 63 (49)
Race .2
White 66 (62) 41 (38) 107 (83)
Black 11 (92) 1 (8) 12 (9)
Asian 2 (100) 0 (0) 2 (2)
Other/unknown 5 (63) 3 (37) 8 (6)
Maternal age (years) .43 (0.61,3.36)
< 35 48 (68) 23 (32) 71 (55)
≥ 35 29 (60) 19 (40) 48 (37)
Unknown 7 (70) 3 (30) 10 (8)
Prenatal diagnosis <.001
Yes 10 (100) 0 (0) 10 (8)
Suspected 30 (77) 9 (23) 39 (30)
No 33 (52) 31 (48) 64 (50)
Unknown 11 (69) 5 (31) 16 (12)
Birth weight category .14
SGA 18 (82) 4 (18) 22 (17)
AGA 62 (61) 39 (39) 101 (78)
LGA 2 (50) 2 (50) 4 (3)
Unknown 2 (100) 0 (0) 2 (2)
Birth weight (grams) .25
< 1,500 5 (100) 0 (0) 5 (4)
1,500–2,500 17 (77) 5 (13) 22 (17)
> 2,500 60 (60) 40 (40) 100 (78)
Unknown 2 (100) 0 (0) 2 (1)
Gestational age (weeks) .06
≥ 37 64 (62) 39 (38) 103 (80)
34–36 11 (65) 6 (35) 17 (13)
< 34 9 (100) 0 (0) 9 (7)

Abbreviations: AGA, appropriate for gestational age; CI, confidence interval; ICU, intensive care unit;
LGA, large for gestational age; SGA, small for gestational age.

first year of life. Only 3 (10%) were normal, 24 (83%) had obstructive
sleep apnea based on obstructive index, and 2 (7%) patients had evi-
dence of hypoventilation and hypoxemia not related to sleep apnea.
Of the 24 patients with confirmed sleep apnea during the first year of
life, 7 received that diagnosis in the neonatal period. Table 4 evaluates
the prevalence of CHD and the types of cardiac lesions associated
with the need for ICU care. Of the patients with a complete or partial
AV canal, one underwent surgical palliation during the neonatal
period. Three patients within this category also had a comorbidity of
duodenal atresia, one had posterior urethral valves, and one had
esophageal atresia. The majority of patients with an AV canal defect,
17/22 (77%), had no other anatomic abnormalities that would have
necessitated ICU care after delivery, and thus required ICU care for
medical issues such as feeding difficulties and respiratory insufficiency.
Twenty-four patients (19%) required ICU admission due to the
need for surgical intervention in the neonatal period. Seven patients
underwent cardiac repair, 14 patients had gastrointestinal surgery for
conditions including duodenal atresia, Hirschsprung disease, anorectal
malformations, omphalocele, and umbilical hernia, two had ENT pro-
cedures, and one had ablation of posterior urethral valves.
4 SEITHER ET AL.

TABLE 2 Prenatal diagnosis

Prenatal diagnosis status
predictors
Confirmed Suspected No Unknown

n (%) n (%) n (%) n (%) p

Study cohort 10 (8) 39 (30) 64 (50) 16 (12)
Maternal age (years) .35
< 35 6 (8) 19 (27) 41 (58) 5 (7)
≥ 35 4 (8) 20 (42) 20 (42) 4 (8)
Unknown 0 0 3 (30) 7 (70)
Service market .15
Primary 3 (4) 25 (36) 39 (56) 3 (4)
Referral 7 (12) 14 (24) 25 (42) 13 (22)
Race .09
White 7 (7) 30 (28) 54 (51) 16 (14)
Black 2 (17) 6 (50) 4 (33) 0 (0)
Asian 1 (50) 0 (0) 1 (50) 0 (0)
Other/unknown 0 (0) 3 (38) 5 (62) 0 (0)
Structural heart defect <.01
I. Complex lesion 4 (29) 7 (50) 2 (14) 1 (7)
II. AV canal 4 (16) 12 (48) 6 (24) 3 (12)
III. ASD/VSD/PDA 0 (0) 15 (23) 42 (66) 7 (11)
IV. Other 1 (9) 3 (27) 6 (55) 1 (9)
Duodenal atresia 1 (12) 3 (33) 2 (22) 3 (33) .13

Abbreviations: AV, atrioventricular; ASD, atrial septal defect; PDA, patent ductus arteriosus; VSD,
ventricular septal defect.

Nearly half of the study participants, 59 (46%), were not born in
an eight-county area for which CCHMC serves as the primary
provider for pediatric specialty care and had traveled to CCHMC for
care. These infants were referred to our institution for a variety of
reasons, including management of complex upper airway anomalies,
cardiac surgery, multidisciplinary aerodigestive evaluation, and devel-
opmental follow up through the Thomas Center for Down Syndrome
Services. Further analysis was done to compare those patients from
our primary service area versus those traveling to CCHMC for care;
Table 5 compares these two populations.
4 | DISCUSSION
A majority of patients in our cohort, 55%, were born to mothers under
the age of 35, which is unsurprising as the majority of pregnancies
occur in women in this age group (ACOG, 2016). During the study
period, The American College of Obstetricians and Gynecologists
(ACOG) recommended cell free DNA testing as the preferred screen-
ing method for aneuploidy in high risk pregnancies and integrated
screening for low risk pregnancies, both with detection rates >95% in
their respective populations, with invasive testing then considered for
anyone with a positive screen. They also stated that all pregnant
women should have the option to undergo amniocentesis or chorionic
villus sampling as a first line test, with or without prior screening
(ACOG, 2007b; ACOG, 2012). Despite this fact, a minority of patients
(8%) received a prenatal diagnosis or even a positive screening test
(30%), see Table 1. This is likely related to our regional population as
there is known regional variation in uptake of aneuploidy screening
and prenatal invasive diagnostic testing. This phenomenon was
highlighted in a recent study that demonstrated a significantly lower
rate of noninvasive prenatal screening in the Midwest compared to
the Western and Eastern United States (Platt et al., 2014). Further-
more, when an ultrasound abnormality was present, patients in the
Midwest were more likely to opt for noninvasive prenatal screening
versus invasive diagnostic testing, which was in contrast to the west-
ern cohort (Platt et al., 2014). These findings reflect regional differ-
ences in women's goals and values as well as providers' approaches
surrounding aneuploidy screening and diagnostic testing, which
involve a balance between the need for informational accuracy and
the perception of risk of invasive prenatal testing (ACOG, 2016; Seror
et al., 2019). During the study period, cell free DNA testing, integrated
screening, as well as invasive testing with amniocentesis and chorionic
villus sampling were available in the Cincinnati area and were covered
by both private payers and Medicaid. Therefore, our low rates of pre-
natal diagnoses were not related to a lack of availability or insurance
coverage. A recent study from Ireland conducted over a similar time
period showed a low rate of prenatal diagnosis of 26% in 124 patients,
SEITHER ET AL. 5

T A B L E 3 Medical diagnoses in the

ICU admission
neonatal period
Yes No

Diagnostic category (n, %) (n, %) p 95% CI

Pulmonary <.01 (0, 0.03)
Respiratory distress/failure 46 (55) 0 (0) <.01 (0, 0.08)
Obstructive sleep apnea 7 (8) 0 (0) .1 (0, 1.26)
Airway anomalies 9 (11) 0 (0) .03 (0, 0.90)
Gastrointestinal <.01 (0.04, 0.24)
Poor feeding 52 (62) 10 (22) <.01 (0.07, 0.43)
Dysphagia 5 (6) 1 (2) .66 (0.01, 3.38)
Duodenal atresia 9 (11) 0 (0) .03 (0, 0.90)
Hirschsprung disease 2 (2) 2 (4) .61 (0.13, 27.01)
Hematology .26 (0.28, 1.43)
Polycythemia 6 (7) 1 (2) .42 (0.01, 2.58)
Hyperbilirubinemia 22 (26) 12 (26) 1 (0.41, 2.49)
Thrombocytopenia 9 (11) 2 (4) .33 (0.04, 2.01)
Nephrology <.01 (0.01, 0.55)
Acute kidney injury 5 (6) 0 (0) .16 (0, 2.01)
Hydronephrosis 4 (5) 0 (0) .3 (0, 2.81)
Other renal/GU anomalies 14 (16) 2 (4) .05 (0.02, 1.10)
Endocrinology 1 (0.17, 3.14)
Hypoglycemia 4 (5) 2 (4) 1 (0.08, 6.80)
Hypothyroidism 5 (6) 2 (4) 1 (0.07, 4.73)
Neurology .01 (0, 0.78)
Hypotonia 5 (6) 0 (0) .16 (0, 2.01)
Hypothermia 5 (6) 0 (0) 1.16 (0, 2.01)
Infectious disease .01 (0, 0.61)
Any infection 12 (14) 0 (0) .01 (0, 0.61)

Abbreviations: CI, confidence interval; GU, genitourinary; ICU, intensive care unit.

T A B L E 4 Effect of congenital heart

ICU admission
disease on ICU admission status
Yes No Total

n (%) n (%) n (%) p 95% CI

Any heart disease 77 (68) 37 (32) 114 (88) .15
I. Complex lesion 13 (93) 1 (7) 14 (12) <.01 (0.66, 1.00)
II. AV canal 22 (88) 3 (12) 25 (22) <.01 (0.69, 0.97)
III. ASD/VSD/PDA 32 (50) 32 (50) 64 (56) 1 (0.38, 0.63)
IV. Other 9 (82) 2 (18) 11 (10) .04 (0.52, 0.98)
V. Pulmonary hypertension 20 (91) 2 (9) 22 (17) <.01 (0.71, 0.99)
With structural heart disease 19 (90) 2 (10) 21 (95) 1
Without structural heart disease 1 (100) 0 (0) 1 (5)
VI. Heart failure 11 (100) 0 (0) 11 (8.5) <.01 (0.72, 1.00)

Abbreviations: ASD, atrial septal defect; AV, atrioventricular; CI, confidence interval; ICU, intensive care
unit; PDA, patent ductus arteriosus; VSD, ventricular septal defect.
6 SEITHER ET AL.

T A B L E 5 Comparison of local versus

Primary (n, %) Referral (n, %) p 95% CI
referral populations
Total 70 (54) 59 (46)
ICU admission 41 (58) 43 (73) .1 (0.85, 4.32)
Surgery (neonatal period) 12 (17) 7 (12) .46 (0.20, 1.96)
Cardiac diagnosis (any) 68 (97) 46 (78) <.01 (0.01,0.50)
I. Complex lesion 5 (7) 9 (15) .34 (0.61, 5.05)
II. AV canal 12 (17) 12 (20) .16 (0.65, 9.41)
III. ASD/VSD/PDA 43 (61) 21 (35) .66 (0.46, 3.31)
IV. Other 8 (11) 3 (5) <.01 (0.16, 0.75)
V. Pulmonary hypertension 9 (13) 12 (20) .23 (0.07, 1.85)
Prenatal diagnosis
Confirmed 3 (4) 7 (12) .18 (0.64, 18.73)
Suspected 25 (36) 11 (19) .05 (0.16, 0.96)
No 39 (56) 23 (39) .08 (0.24, 1.09)
Length of stay (mean days) 23 ± 22 35 ± 36 .02 (2.38, 22.62)
Gestational age (mean weeks) 38 ± 2 37 ± 2 .58 (−0.49, 0.89)
Birth weight (mean kg) 2.9 ± 0.6 2.9 ± 0.7 .53 (−0.15, 0.29)

Abbreviations: ASD, atrial septal defect; AV, atrioventricular; CI, confidence interval; ICU, intensive care
unit; kg, kilograms; PDA, patent ductus arteriosus; VSD, ventricular septal defect.

however, for patients with anomalies on prenatal ultrasound, the diag-
nosis rate increased to 56% (Martin et al., 2018). Within our study
cohort, the presence of a structural heart defect was the only variable
significantly associated with a known or suspected prenatal diagnosis
of Down syndrome (p < .01). Duodenal atresia, diagnosed in nine
patients, did not influence prenatal diagnosis status (p = .13). Women
>35 years of age were not more likely to receive a prenatal diagnosis
(p = .35). Confirmed or suspected prenatal diagnosis of Down syn-
drome was significantly associated with ICU admission, p < .01, which
is likely related to a more severe phenotype with fetal anomalies
noted on prenatal imaging.
The study cohort had an even distribution of male and female and
was majority white. The overall racial distribution was similar to the
population for Ohio. A significant proportion of patients (20%) were
born at less than 37 weeks gestation, which is nearly double the pre-
term birth rate for all U.S. born infants (Martin, Hamilton, Osterman,
Driscoll, & Drake, 2018). International studies of preterm birth rates
for newborns with Down syndrome have ranged from 9 to 29%
(Ergaz-Shaltiel et al., 2017; Mann et al., 2016; Martin, Smith,
et al., 2018; Glasson, Jacques, Wong, Bourke, & Leonard, 2016.) The
indication for preterm birth was approximately equally distributed
between maternal and fetal factors.
A majority, 65%, of all subjects required intensive care in the neo-
natal period. While prematurity rates were 20%, prematurity was not
significantly associated with the need for ICU care (see Table 1) and
62% of all term infants still required ICU care. In previous international
studies, rates of ICU admission have ranged from 35 to 80% (Ergaz-
Shaltiel et al., 2017; Martin, Smith, et al., 2018). While 19% of the
cohort required ICU care due to an anatomic abnormality that
required surgical correction, the major of patients required ICU care
for medical indications. The most common medical indications for ICU
admission, excluding cardiac diagnoses, were poor feeding (62%) with
eight requiring gastrostomy tubes in the neonatal period, respiratory
distress (55%) with 1 requiring extracorporeal membrane oxygenation
cannulation for refractory respiratory failure, jaundice (26%), and
infections (14%).
A majority of the cohort (n = 114, 88%) had at least one structural
or functional cardiac defect. Specific categories of cardiac abnormali-
ties (types I complex lesions, II AV canals, and V pulmonary hyperten-
sion) were significantly associated with the need for ICU admission
(p < .01, p < .01, p < .01). When patients with any CHD were analyzed
as a whole, however, there was no statistically significant increased
need for ICU care, likely owing to the 56% of patients with a type III
lesion (ASD/VSD/PDA) that did not influence ICU admission status.
Interestingly, 25 patients had a type II lesion (AV canal) and 22 (88%)
required ICU admission. An AV canal is not thought to be symptom-
atic in the neonatal period due to persistently elevated pulmonary
pressures preventing immediate over circulation and development of
heart failure symptoms. When diagnosed prenatally, families are rou-
tinely counseled that this type of defect can be followed up by cardi-
ology on an outpatient basis and that their infant will not require ICU-
level care. While surgical repair in the neonatal period may rarely be
indicated for an AV canal (only 1 patient required neonatal interven-
tion in this cohort, a palliative procedure in the setting of severe com-
mon AV valve regurgitation), it does predict difficulties navigating the
neonatal period and has a significant positive association with needing
ICU care. Within our cohort, 17% of patients (n = 22) carried a diagno-
sis of pulmonary hypertension; all but one of these patients also had a
structural heart defect. The presence of pulmonary hypertension,
regardless of its etiology, had a significant positive association with
SEITHER ET AL.
the need for ICU care (p < .01). A recent study by T. Martin and col-
leagues noted pulmonary hypertension in 34% of newborns with
Down syndrome and an equal incidence in patients with and without
a structural cardiac lesion (2018). They also demonstrated that having
pulmonary hypertension increased the risk for needing invasive
mechanical ventilation, longer duration of ICU care, and an increased
risk of death (Martin, Smith, et al., 2018).
The prevalence of Down syndrome nationally is reported to be
approximately 1:700; the prevalence calculated for our cohort was
1:734, indicating that nearly all patients with Down syndrome born in
the Cincinnati area were captured in this study. The American Academy
of Pediatrics recommends that all patients with Down syndrome
undergo postnatal echocardiography (Bull, 2011). In the Cincinnati area,
CCHMC is the only institution providing pediatric echocardiography;
therefore, we would predict that patients born in our local market
would have at a minimum had a point of contact with CCHMC for an
echocardiogram. Both of these facts would indicate that the findings of
this study accurately describe the health outcomes for a regional, unbi-
ased cohort of newborns and infants with Down syndrome.
While this study has many strengths, it has a few inherent limita-
tions. Most prominently, the study was retrospective and data collec-
tion was limited to only what was available in the CCHMC EMR;
maternal medical records were not queried and documentation from
outside institutions was inconsistently accessible. The study is also
dependent upon accurate information being entered into the EMR
and there was no way to validate the data. The final limitation is in
the timing of data collection with study participants being born
between 2013 and 2014. Since this time, cell free DNA testing has
been expanded to both high and low risk populations, which may have
led to a higher proportion of patients with a positive screening test
and possibly a higher rate of confirmatory invasive testing; however
there have been no new prenatal or postnatal interventions for Down
syndrome or management guidelines that would have changed cur-
rent health outcomes for infants with Down syndrome. Despite these
limitations, this study is the first to characterize a U.S born cohort of
infants with Down syndrome, their neonatal outcomes, and factors
necessitating ICU care.
5 | C O N CL U S I O N S
The majority of newborns with Down syndrome have significant early
complications that require ICU care. Many have anatomical abnormali-
ties that require surgical correction; however, most are requiring
advanced care for medical reasons including respiratory difficulties,
feeding problems, infections, and cardiac disease not requiring early
surgical correction. Given the high incidence of critical care needs
demonstrated by this study and others, the ideal location for delivery
of a baby with Down syndrome would be at an institution with level
III or IV neonatal ICU capabilities given that the majority are requiring
intensive care. This would allow for mother and infant to remain in
the same institution and facilitate parental bonding as well as parent
and care provider communication even when ICU admission is
7
warranted. In order to better prepare families for this early neonatal
experience, a prenatal diagnosis is imperative. Unfortunately, this is
not happening as often as is possible in live born infants with Down
syndrome. A prenatal Down syndrome diagnosis directs obstetrical
providers to perform more detailed imaging via ultrasound and fetal
echocardiography to look for anatomical complications, refer the fam-
ily for genetic counseling, and involve pediatric consultants such as
neonatologists, cardiologists, and pediatric surgeons to develop an
appropriate delivery plan and to educate the family about the health
challenges their child may face. This type of thorough prenatal evalua-
tion allows those families that choose to continue the pregnancy to
be prepared for the medical challenges encountered by many neo-
nates with Down syndrome.
For newborns with Down syndrome, the challenges of the neonatal
period are complex, but can be categorized into anatomic abnormalities,
functional abnormalities including respiratory difficulties and feeding
difficulties, and intrinsic problems related to infectious risk and
jaundice. While the functional and intrinsic abnormalities cannot yet
be accurately accessed prenatally, the anatomic abnormalities can,
and should be carefully sought out and characterized to provide an
accurate risk assessment for neonatal ICU care based on anatomic
findings. For those patients without anatomic problems requiring
immediate ICU care after birth, it is imperative that neonatal providers
carefully monitor for respiratory and feeding difficulties and rapidly
address these concerns. Down syndrome patients should be moni-
tored closely for signs of infection, and serum bilirubins should be
obtained routinely at 24 hr of life when the newborn screen is
performed or sooner if there are clinical signs of jaundice (Ram &
Chinen, 2011).
This is the first study to comprehensively evaluate a U.S. born
cohort of Down syndrome patients, and further multicenter studies
will be needed to evaluate rates of prenatal diagnosis and neonatal
complications across a more diverse cohort. The knowledge obtained
from this study will be used to write evidence based neonatal man-
agement guidelines for Down syndrome, which will help to standard-
ize neonatal care for this important population.
ACKNOWLEDG MENTS
Automated data extraction from the EMR were provided by the
Data & Technology Services team at Cincinnati Children's Hospital
Medical Center. Greg Muthig provided data management support for
the project. The authors would like to thank the Perinatal Institute at
Cincinnati Children's Hospital Medical Center for their support of
this work.
CONFLIC T OF INT ER E ST
The authors confirm that they have no conflicts of interest related to
this work or its publication.
DATA AVAILABILITY STAT EMEN T
Data Availability Statement: The authors elect not to share data
that support the findings of this study due to privacy or ethical
restrictions.
8 SEITHER ET AL.
ORCID
Katelyn Seither https://orcid.org/0000-0002-8204-7667
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How to cite this article: Seither K, Tabbah S, Tadesse DG,
Suhrie KR. Neonatal complications of Down syndrome and
factors necessitating intensive care. Am J Med Genet Part A.
2020;1–8. https://doi.org/10.1002/ajmg.a.61948