Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315282 on 27 September 2018. Downloaded from http://fn.bmj.
com/ on 1 October 2018 by guest. Protected by
1
Department of Neonatology,
University Children’s Hospital
Tübingen, Tübingen, Germany
2
Center for Paediatric Clinical
Studies, University Children’s
Hospital, Tübingen University
Hospital, Tübingen, Germany
3
Department of Paediatric
Surgery and Pediatric Urology,
University Children’s Hospital
Tübingen, Tübingen, Germany
Correspondence to
Dr Yasemin Yarkin, Department
of Neonatology, University
Children’s Hospital, Tübingen
72076, Germany; ​Yasemin.​
Yarkin@​med.​uni-t​ uebingen.​de
Received 3 April 2018
Revised 31 July 2018
Accepted 28 August 2018
© Author(s) (or their
employer(s)) 2018. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Yarkin Y, Maas C,
Franz AR, et al. Arch Dis Child
Fetal Neonatal Ed Epub
ahead of print: [please
include Day Month Year].
doi:10.1136/
archdischild-2018-315282
Epidemiological study on intestinal volvulus without
malrotation in VLBW infants
Yasemin Yarkin,1 Christoph Maas,1 Axel R Franz,1,2 Hans-Joachim Kirschner,3
Christian F Poets1
Abstract
Background  We conducted a monthly epidemiological
survey in Germany to detect the prevalence of volvulus
without malrotation (VWM) in very low birthweight
(VLBW) infants and to identify factors for a better
distinction between this rare and life-threatening event
and other acute abdominal diseases in preterm infants.
Methods  Throughout 2014 and 2015, every paediatric
department in Germany was asked to report cases of
VWM in infants with birth weights <1500 g to the
Surveillance Unit for Rare Paediatric Conditions in
Germany. Hospitals reporting a case were asked to
return an anonymised questionnaire and discharge letter.
Results  Of 36 cases reported, detailed information was
submitted on 29, with 26 meeting entry criteria. With
9896 and 10 140 VLBW infants born in Germany in
2014 and 2015, respectively, we estimated a prevalence
of 1.52/1000 VLBW infants for 2014 and 1.08/1000 in
2015. No specific early symptom could be determined.
10% died, and 21% of infants developed short bowel
syndrome. Calculated from all verified VWM arise death
in 8% and a short bowel syndrome in 15%.
Conclusion  VWM is a rare source of acute abdomen
in VLBW infants. No specific signs and symptoms
potentially facilitating an early recognition of VWM could
be found from this survey. Because the rates of death
and short bowel syndrome are high, VWM should always
be considered early in an acute abdomen in a VLBW
infant.
Introduction
Volvulus without malrotation (VWM) represents
a life-threatening event in premature infants. Case
series describe its occurrence typically in very low
birthweight (VLBW) infants and several weeks
after birth.1 2 VWM generally presents as an acute
abdomen with a rapid and dramatic deterioration
of the infant’s general condition.3 Especially in the
vulnerable population of very preterm infants, an
early diagnosis, that is, before the occurrence of
irreversible intestinal ischaemia, is difficult due to
a rapid progression of ischaemic bowel damage and
non-characteristic early clinical signs or imaging
findings.4 Furthermore, VWM may be mistaken for
the more common entity of necrotising enterocolitis
(NEC) in VLBW infants.5 6 Conservative treatment
for suspected NEC delays surgical intervention6
thereby aggravating morbidity and mortality.
A VWM requires immediate surgical treatment
to restore intestinal blood supply and to avoid irre-
versible ischaemic bowel damage. Ischaemia of the
twisted bowel is supposed to develop more rapidly
Yarkin Y, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F4. doi:10.1136/archdischild-2018-315282
Original article
What is already known on this topic?
►► Volvulus without malrotation (VWM) is a rare
and life-threatening disease, needing immediate
surgical intervention to prevent mortality and
short bowel syndrome.
What this study adds?
►► This study shows that VWM occurs in
1–1.5/1000 infants <1500 g, more often than
expected.
►► Differentiation to other abdominal diseases
remains difficult and challenging.
in VWM because of the normal position and fixa-
tion of the uninvolved colon, whereas in cases of
copyright.
volvulus with malrotation and a mobile caecum,
the colon may attenuate ischaemia and sequelae of
the small bowel torsion.3 Both incidence and aeti-
ology of VWM are unknown.3 In preterm infants,
respiratory support with continuous positive airway
pressure (CPAP) as well as abdominal massage and
pelvic rotation have been suspected as risk factors.1 2
We performed a prospective epidemiological
study in Germany (1) to determine the incidence
of VWM in VLBW infants, (2) to detect potential
‘red flag’ signs and symptoms of this disease, (3) to
gather information on risk factors and (4) to poten-
tially develop preventive strategies.
Patients and methods
As part of the Surveillance Unit for Rare Paediatric
Conditions in Germany (ESPED), all paediatric
departments (459 in 2014 and 409 in 2015) received
monthly reporting cards asking them about new
admissions of preterm VLBW infants with VWM
admitted between January 2014 and December
2015. Reports on the mailing card prompted
immediate mailing of an anonymised three-page
questionnaire. Electronic reminders were sent to
all non-responders. In case of persistently missing
completed questionnaires, the study centre also
contacted the local person responsible for the
ESPED collaboration to maximise response rates.
Captured were all preterm infants with a birth
weight of <1500 g who had suffered an intestinal
VWM. VWM had been defined as any finding of
volvulus on laparotomy, where the duodenal rota-
tion/fixation was confirmed as normal (also known
   F1

Original article
as ‘segmental volvulus’). In general, reporting completeness of
the ESPED system exceeds 95%.
Data collection
The anonymised three-page questionnaire designed by our group
asked for basic demographic data, information about pregnancy,
perinatal medical history and the clinical course during the
postnatal hospitalisation. The latter included details on clinical
signs, diagnostic imaging and laboratory findings on the day of
volvulus presentation and on parameters of gastrointestinal func-
tion and enteral nutrition, manipulations intended to promote
bowel function, as well as respiratory support received prior
to the event. Furthermore, details on intraoperative findings,
including the extent of bowel resection (if any) and the postop-
erative outcome were obtained, as was an anonymised copy of
the infant’s discharge letter. Based on these data, duplicate cases
or those not meeting inclusion criteria were excluded.
Statistical analyses
As this is an explorative study without a primary hypothesis,
no sample size calculation was done. Descriptive statistics were
applied to characterise the study population. Data are presented
as median (range).
Results
Between January 2014 and December 2015, a total of 36
cases of VWM in VLBW infants were reported to the study
centre; detailed information was supplied in 29 cases, yielding
a response rate of 81%. Unfortunately, several respondents did
not provide answers to all questionnaire items. Response rates
for single questionnaire items ranged from 40% to 100%
Of the 29 cases with detailed information, 26 could be verified
(15 in 2014 and 11 in 2015) while three with diagnosis other
than VWM were excluded.
Given a birth rate of 9896 preterm VLBW infants in 2014 and
10 140 in 2015 in Germany (according to the German Federal
Statistical Office) and assuming complete reporting, an inci-
dence of intestinal VWM of 1.29/1000 VLBW infants (95% CI
1.08 to 1.51) was estimated: 1.52/1000 in 2014 and 1.08/1000 in
2015. All diagnoses of VWM were made on surgery. Eighty-one
per cent (21/26) of the affected infants were predominantly
of extremely low gestational age (<28 weeks); they presented
at a median postnatal age of 27 days. Median Apgar values at
1/5/10 min were 6/7/9; median umbilical artery pH was 7.34.
Five infants were twins; 54% were girls. Detailed demographic
data are shown in table 1.
Prenatal ultrasound and neonatal data
Prenatal ultrasound findings were reported as suspicious in
only two cases who had dilated echogenic bowels and absent
peristalsis. One of these infants also had a whirlpool sign and
underwent laparotomy immediately after birth, on which 32 cm
Table 1  Demographic data
Number of infants 26
Gestational age at birth (median; range) (weeks) 25.9 (23–32)
Birth weight (median; range) (g) 728 (450–1480)
PMA at VWM onset (median; range) (weeks)* 31 (26–46)
PMA at VWM onset (median; range) (days)* 27 (−2–149)
Data are median (minimum–maximum).
*Diagnosis/VWM onset=day of surgery, except in one prenatal suspicion.
PMA, post menstrual age; VWM, volvulus without malrotation.
F2
Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315282 on 27 September 2018. Downloaded from http://fn.bmj.com/ on 1 October 2018 by guest. Protected by
of necrotic bowel was removed. Although she subsequently
developed short bowel syndrome (SBS), she could be discharged
on full enteral feeds. The other infant had laparotomy 13 days
postnatally, 2 days after first becoming symptomatic for VWM.
No information on intraoperative findings or the postopera-
tive course was supplied. No polyhydramnions or ascites was
reported antenatally, but four had pathological Doppler signals.
Enteral intake and stooling before diagnosis of VWM
Information on enteral feeding before the event was available
for 22 infants, half of which were solely fed with mother’s milk;
in five infants, a fortifier had been added. Five infants were
only formula fed, while six had received both breast milk and
formula. The median time interval from birth until full enteral
feeding was achieved was 20 days (range 6–60; 16 responses).
The time interval from birth until the last meconium-like stool
was passed was 7 days (range 2–20). Tolerance to enteral feeding
was unremarkable before the event, except for four patients who
had bilious and two patients who had bloody gastric residues
reported within the last 5 days before the event. Support given
for stooling in the last 5 days before the event had been reported
for 15 infants included enemas (n=14), abdominal massage
(n=12) and/or a rectal tube (n=6). Only six patients were
reported to defecate completely spontaneously. One patient was
operated directly after birth without any support attempts. For
four patients, information is lacking.
Respiratory support
At time of VWM diagnosis, most infants had received support
via nasal CPAP. The highest positive end expiratory pressure
copyright.
(PEEP) used ranged from 4 to 8 cm H2O, with a median of 6 cm
H2O (table 2).
Clinical and radiological signs
Clinical signs at presentation were dominated by rather
unspecific findings except that they pointed to a gastrointestinal
problem (table 3).
Radiological and ultrasound findings are described in table 4.
The most common finding on ultrasound as well as on plain
radiographs was dilated bowel loops followed by a suspicious
configuration of bowel loops on plain radiographs. No specific
imaging findings were recognised, and a whirlpool sign was
hardly ever reported.
Time to laparotomy, intraoperative and postoperative
findings
In eight infants, laparotomy was performed on the day when
symptoms of VWM were first noticed, in seven infants lapa-
rotomy was done on day 1, in four infants on day 2, in two infants
on day 4 and in one infant each on days 5, 6 and 22, respectively,
after onset of clinical signs. In two infants the timing of lapa-
rotomy in relation to onset of clinical signs was not reported.
Table 2  Type and proportion of respiratory support before diagnosis
of VWM
Total number reported 25
Nasal CPAP (n (%)) 14 (56)
Mechanical ventilation via endotracheal tube (n (%)) 6 (24)
High-flow nasal cannula (n (%)) 2 (8)
No respiratory support (n (%)) 3 (12)
CPAP, continuous positive airway pressure; VWM, volvulus without malrotation.
Yarkin Y, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F4. doi:10.1136/archdischild-2018-315282
 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315282 on 27 September 2018. Downloaded from http://fn.bmj.com/ on 1 October 2018 by guest. Protected by
Original article
nutrition at discharge, two were on full enteral feedings and in
Table 3  Main symptoms on the day of VWM diagnosis
one infant information on this item is missing.
Total number reported 26
Acute abdominal distension, n (%) 18 (69)
Deterioration of general clinical situation, n (%) 17 (65) Discussion
Bile-stained nasogastric aspirates, n (%) 10 (38) We wanted to determine the prevalence of VWM in Germany
Aggravation of apnoea of prematurity, n (%) 9 (35) and identify specific signs that would help to distinguish VWM
Increased lactate levels, n (%) 9 (35) from more common conditions like NEC or spontaneous intes-
Constipation, n (%) 9 (35) tinal perforation in preterm infants. We were notified of 26
Metabolic acidosis, n (%) 8 (31)
confirmed cases over a 2-year study period, yielding a prevalence
Abdominal wall erythema/oedema, n (%) 4 (15)
of about 1.3/1000 VLBW infants in Germany. To our best knowl-
edge, this is the first report on population-based prevalence data
Bloody stools, n (%) 3 (11)
of VWM in VLBW infants. For comparison, a British neonatal
Unusually protracted screaming attack, n (%) 3 (11)
surgical service reported only one case of VWM in a series of
Vomiting, n (%) 2 (8)
57 emergency laparotomies in extremely low gestational age
Stool-containing gastric residues, n (%) 1 (4)
neonates, indicating that other causes of acute abdomen domi-
VWM, volvulus without malrotation. nate by far.7
In contrast to previous case series, VWM occurred equally
often in girls and boys, and comparatively late after birth:
Two infants had received a laparotomy prior to VWM, one for median age here was 27 days, whereas in the other report, the
stomach perforation on postnatal day 8, and 90 days later the median age was about 20 days.1–6 8–10 Yet, patients in this survey
laparotomy was carried out because of a VWM. were born at a lower gestational age (25.9 weeks). The median
The other underwent an explorative laparotomy because of an gestational age in previously reported case series was about 28
ileus symptomatology on the 55th day of life, and 94 days later weeks.1–6 8–10 Because this survey focused on VLBW infants, our
needed a laparotomy because of VWM. study group was more premature. Prenatal manifestation of
In 14 of 24 cases with information provided, volvulus had
volvulus, as here reported for two infants, has been reported
been suspected preoperatively; in the remaining infants, the
before.9 The diagnosis of VWM was made during laparotomy
diagnosis was only made intraoperatively.
27 (0–149) days after birth. In this survey, there was no apparent
Intraoperative findings besides volvulus were an ovarian cyst,
relationship between postnatal age at surgery and severity of
a microcolon, a missing fixation with a mobile colon and Meck-
outcome. Infants who died had onset of clinical signs on post-
el’s diverticulum and a segmental intestinal stenosis of 2 mm in
natal day 82 (64–99), and all had laparotomy on the day of

copyright.
length (in one infant each).
initial presentation.
Eighteen of 25 infants (72%) had a bowel resection ranging
Infants with delayed surgery (first surgical intervention more
from 4 cm to resection of the entire small intestine (median:
than 1 day after onset of symptoms) had favourable outcomes
23 cm); information on bowel resection was missing in one
(all survived without (temporary) SBS). However, this should
infant.
not be interpreted as an indication to postpone surgical inter-
Eleven infants required a second laparotomy, two had two
vention; to the contrary, infants with delayed surgical interven-
relaparotomies. Although a second laparotomy could be part of
tions probably had less severe twisting of the intestine and hence
a surgical strategy to allow as much ischaemic bowel as possible
preserved blood flow.
to recover before definite decision for resection, this strategy
Clinical presentation was that of an acute abdomen without
was not applied in this cohort. Eighteen patients survived, while
any VWM-specific signs. Similarly, recent case reports did not
two died shortly after laparotomy (six infants with missing data).
identify specific clinical sign that could help identify VWM. In
Four infants developed a SBS (SBS was defined as discharge with
our study, the main clinical symptoms were acute abdominal
partial parental nutrition); one of these was on total parenteral
distension (69%), acute deterioration of the infants’ general
condition (65%) and suddenly increased bilious gastric resid-
uals (38%).
Table 4  Abdominal imaging findings on the day of VWM diagnosis Respiratory support via CPAP has been discussed as a risk
Total number reported 26 factor for VWM.9 Fifty-six per cent of the infants in this cohort
Radiographic findings (n (%)): had respiratory support with CPAP the day before VWM mani-
 Dilated loops of bowel 15 (58) festation, but at PEEP levels well within the expected range,
 Suspicious configuration of bowel loops 11 (42) given that most infants were born <32 weeks and only about 3–4
 Bowels with air fluid level 9 (35) weeks old. Due to the lack of a matched control group in this
 Free intraperitoneal gas 4 (15) study, it remains uncertain whether respiratory support (CPAP
 Pneumatosis intestinalis 3 (12)
in 56% of patients) or any other respiratory support are indeed
risk factors or just normal for this patient population. Our own
 Intestinal wall oedema 2 (8)
series of VWM previously published along with control infants
Sonographic findings (n (%)):
matched for gestational age at birth, sex, birth year and postnatal
 Dilated bowel loops 14 (54)
age at birth, however, indicated that more intense positive pres-
 Free intra-abdominal fluid 8 (31)
sure support might contribute to VWM.10
 Pneumatosis intestinalis 2 (8)
As also reported by others,3 4 neither radiological imaging
 Pneumatosis hepatis (portal venous gas) 1 (4) nor ultrasound examination was successful in detecting volvu-
 Intestinal wall oedema 1 (4) lus-specific features. Intramural gas was reported in three cases.
 Whirlpool sign 1 (4) A whirlpool sign was only found in the infant where this had
VWM, volvulus without malrotation. already been diagnosed prenatally.
Yarkin Y, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F4. doi:10.1136/archdischild-2018-315282 F3

Original article
In our experience, intestinal gas frequently prevents visual-
isation of the superior mesenteric artery sufficiently to detect/
rule out the whirl pool sign during abdominal ultrasound in
infants with acute abdomen.
The common practice of abdominal massage has also been
associated with volvulus.1 2 This was also here reported for 12
of 15 infants, but its relevance to volvulus remains unclear given
our uncontrolled study design.
In seven infants, surgical intervention was fast enough to
avoid any bowel resections; at least 4 of these infants were even-
tually discharged home. One infant had no resection performed
despite more than 90% of the intestine being ischaemic. This
infant died of multiorgan failure prior to an intended second-
look operation. Of the 18 infants who did have a bowel resec-
tion, at least 13 were discharged home, although four developed
SBS (15% of all verified VWM cases), with three of the four
continuing to grow normally on full enteral nutrition. In general,
the development of an SBS is rare (0.7%), as shown in a cohort
of 12316 VLBW infants, mainly caused by NEC.11
In the case study of Drewett and Burge, none of the infants
develop an SBS. The total parenteral nutrition lasted a median
of 12.5 days, and all affected infants could be discharged on
full enteral feeding.8 The oral feeding in the study by Billiemaz
et al1 could be started at a median of 11 postoperative days;
14.3% developed an SBS and 71% were discharged with full
oral feeding.
Information on the further course is sparse in other case
reports. Four case studies1 2 6 9 mentioned data on the propor-
tion of SBS with a median value calculated from these reports
of 12.7%.
Mortality (10%) was lower than reported in all previous case
series,1 3 5 6 8 12 but this proportion might underestimate actual
mortality rate as there was no information on survival for six
infants, and therefore a robust conclusion regarding mortality
cannot be made.
Limitations
Our study is hampered by incomplete questionnaire data despite
several attempts to improve response rates and by its uncon-
trolled nature. Nonetheless, it constitutes the first attempt to
generate population-based data on this rare and dramatic event.
Data from other surveillance units that ideally include controls
are urgently awaited.
Conclusion
VWM is a life-threatening disease, resulting in SBS in a substan-
tial proportion of survivors. Differentiation from other acute
abdominal conditions in preterm neonates remains challenging.
Unfortunately, our survey did not identify any specific diagnostic
F4 Yarkin Y, et al. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F4. doi:10.1136/archdischild-2018-315282
Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315282 on 27 September 2018. Downloaded from http://fn.bmj.com/ on 1 October 2018 by guest. Protected by
sign. We also failed to identify clinical or imaging findings that
would make VWM highly unlikely. Therefore, an immediate
explorative laparotomy may be considered in any preterm infant
with signs of an acute abdomen and deterioration of the clinical
situation to prevent irreversible bowel ischaemia.
Acknowledgements  We would like to thank the German Surveillance Unit for
Rare Pediatric Diseases (Erhebungseinheit für seltene pädatrische Erkrankungen in
Deutschland Study Group (ESPED)) and especially Beate Heinrich for their support
and all colleagues from the participating hospitals for reporting their cases.
Contributors  CM designed the study and the questionnaire, supervised data
analyses and reviewed and revised the manuscript making important intellectual
contributions. ARF was study coordinator, contributed to study and questionnaire
design, supervised data analyses and reviewed and revised the manuscript making
important intellectual contributions. YY was responsible for the data collection and
recording and reviewing and revising the questionnaires. H-JK reviewed and revised
the manuscript for important intellectual contributions. CFP supervised the study
as the head of department and reviewed and revised the manuscript for important
intellectual contributions. All authors read and approved the final manuscript.
Funding  The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Disclaimer  The authors have indicated the statements in the submitted article are
their own and not an official position of the institution.
Competing interests  None declared.
Ethics approval  The study protocol, including a parental consent waiver, was
approved by the ethics committee of Tübingen University Hospital.
Provenance and peer review  Not commissioned; externally peer reviewed.
Data sharing statement  There is no additional unpublished data available.
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