PRENATAL DIAGNOSIS

Prenat Diagn 2010; 30: 357–360.

Published online 2 March 2010 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/pd.2490

The Natural History of Anencephaly

Nidaa Obeidi, Noirin Russell, John R Higgins and Keelin O’Donoghue*
Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital,
Ireland

Objective Early elective termination of pregnancy is the most common outcome of a diagnosis of anencephaly
in developed countries. Experience and expertise with management of ongoing pregnancies is limited. We aimed
to investigate the natural history of these pregnancies from diagnosis to delivery and to determine timing of
death.

Method A retrospective review of cases of anencephaly diagnosed between 2003 and 2009 in tertiary-referral
university teaching hospitals in Cork.

Results The majority of cases (25/26; 96%) were diagnosed prenatally at a median gestation of 21+2 weeks
(range 13+4 –32+4 ). The median maternal age was 30 years (range 17–41) and 50% were primigravidae. Seven
pregnancies were complicated by polyhydramnios and four deliveries were complicated by shoulder dystocia.
The median gestation at delivery was 35 weeks (range 22+5 –42+6 ); 69% of labours were induced at a median
gestation of 34 weeks. Six women (6/26; 23%) had a pre-labour intrauterine fetal death and nine women (9/26;
35%) had an intrapartum fetal death. Median neonatal survival time was 55 min (range 10 min to 8 days). Six
parents donated neonatal organs for transplantation.

Conclusion This study provides useful information for health professionals caring for patients with a
diagnosis of anencephaly. The majority of these infants die prior to delivery but short-term survival is possible.
Copyright  2010 John Wiley & Sons, Ltd.
KEY WORDS: anencephaly; intrauterine death; neonatal death; neural tube defects; prenatal diagnosis

INTRODUCTION remaining 5% died before day 6 (Ford, 2002). Common

Anencephaly is a neural tube defect which occurs due to
the failure of normal tube closure at the cranial end of
the 4-week old embryo resulting in the absence of major
portion of brain, skull and scalp. It is estimated to occur
in 1/1000 pregnancies worldwide (Cook et al., 2008).
Historically, Ireland has a relatively high incidence of
neural tube defects when compared to other European
countries (Masterson et al., 1974; Kirke and Elwood,
1984; Elwood and Elwood, 1982), but the prevalence of
anencephaly from 1980 to 2007 was reported as 6.41
per 10 000 births in Ireland, which did not differ sig-
nificantly from other European registries (Busby et al.,
2005; Dolk, 2005).
Stillbirth is a common outcome of fetal anencephaly
but some affected fetuses are born alive. The condition is
uniformly lethal and not treatable. No fetal intervention
is possible and treatment after birth is supportive. How-
ever, little is reported about the natural history of these
pregnancies from diagnosis to delivery, and the timing of
death varies (Baird and Sadovnick, 1987; Anonymous,
1990; Kalucy et al., 1994; Cook et al., 2008). In 1975,
before prenatal diagnosis was widespread, Australian
statistics show that of 180 deaths with anencephaly, 72%
were fetal and 27% neonatal, while of live-born infants,
86% died within a day, 9% died a day later and the
*Correspondence to: Dr Keelin O’Donoghue, Anu Research Cen-
tre, Department of Obstetrics and Gynaecology, University Col-
lege Cork, Cork University Maternity Hospital, Wilton, Cork,
Republic of Ireland. E-mail: k.odonoghue@ucc.ie
maternal complications reported include polyhydram-
nios, dysfunctional labour and postpartum haemorrhage
(Anonymous, 1990).
In 2000 the Royal College of Obstetricians and
Gynaecologists (RCOG) recommended offering a two-
stage programme of a first and second trimester scan to
all women for the detection of fetal anomalies (RCOG,
1997), and ultrasound screening to detect congenital
malformations soon became routine practice. Prenatal
detection of anencephaly by ultrasound is possible in
almost 100% of cases (Johnson et al., 1997; Cameron
and Moran, 2009). Parents and obstetricians increasingly
considered elective pregnancy termination for anen-
cephaly and in countries where this was practiced, the
birth rate of anencephaly fell dramatically (Leck, 1983;
Cuckle et al., 1989; Anonymous, 1991; Omran et al.,
1992; Chan et al., 1993; Cragan et al., 1995; Jaquier
et al., 2006). Of all cases of anencephaly reported by
UK registries between 1980 and 2007, >90% under-
went termination of pregnancy (Dolk, 2005). Ultrasound
has been a key component of prenatal care in Ireland
since the 1990s but there is no consensus on the type of
ultrasound examination that should be offered routinely
or selectively (Lalor and Devane, 2007; Lalor et al.,
2007a). Although clinicians follow guidelines developed
by the RCOG, the practice of fetal anomaly scanning
varies. This is influenced by the fact that termination
of pregnancy is not legally available in Ireland. When
faced with the diagnosis of a lethal congenital malforma-
tion such as anencephaly, the dominant parental choice

Copyright  2010 John Wiley & Sons, Ltd. Received: 14 November 2009
Revised: 21 January 2010
Accepted: 21 January 2010
Published online: 2 March 2010
358
6 20
intra-uterine death
2 4
Spontaneous preterm labour
14
Induction of labour Caesarean section
6 8
Intra-partum death Neonatal death
Figure 1—Natural history of anencephaly
remains continuation of the pregnancy (Byrne and Mor-
rison, 1999; Lalor et al., 2009).
Where parents continue the pregnancy, health profes-
sionals should provide ongoing prenatal care and prepare
the parents for delivery. However, analysis of the expe-
riences of couples those chose to continue the pregnancy
after a diagnosis of a lethal anomaly revealed health pro-
fessionals were ill-prepared to provide appropriate care
in these circumstances (Bartholome, 1994; Chitty et al.,
1996; Jaquier et al., 2006; Lalor et al., 2007b). Varia-
tions in the management of these pregnancies are also
reported. There is uncertainty regarding potential pre-
natal complications and management in labour (Cook
et al., 2008). The timing of induction of labour after
viability is also a dilemma; while some justify the early
induction of labour of anencephalic fetuses, others con-
sider it as direct killing by separating the fetus from its
natural means of life support (Doczy et al., 1993; Ford,
2002; Diamond, 2003).
We studied all cases of anencephaly in order to
evaluate the natural history of these pregnancies after
diagnosis, to explore the antepartum and intrapartum
complications and to determine the timing of death.
METHODS
We conducted an observational study of all pregnancies
where fetal anencephaly was diagnosed between January
Copyright  2010 John Wiley & Sons, Ltd.
N. OBEIDI et al.
26 fetuses
Ongoing pregnancies
induction of labour
1 5
Spontaneous onset of labour
1 1 Preterm
Neonatal death
3 2
Intra-partum death Neonatal death
2003 and October 2009. Records of three separate
maternity hospitals in Cork were searched from 2003
to 2007, when these units amalgamated into Cork
University Maternity Hospital, a university teaching
hospital with around 9000 deliveries per year. Data
were collected from computerized medical records, birth
registers, congenital malformation registers, ultrasound
databases and supplemented by individual chart review.
Retrospective analysis was done as part of clinical audit,
for which local Research Ethics Committee approval
was not required.
During the time period under study, pregnant women
received one prenatal ultrasound scan at 10–14 weeks
of gestation, with fetal anomaly ultrasound scanning
performed on selected cases. Prenatal diagnoses were
confirmed on ultrasound by a fetal medicine specialist
and reviewed after delivery by a neonatologist. Cases
where anencephaly existed with aneuploidy or other
significant anomalies were excluded from the study.
Outcome variables included prenatal complications
(preterm delivery, polyhydramnios, intrauterine death),
mode of onset of labour, length of labour, intrapartum
death, neonatal death and length of survival. Poly-
hydramnios was defined as ultrasound estimation of
amniotic fluid index >25 cm and preterm delivery as
<37 weeks of gestation. Data were analysed using
Microsoft Excel 2004.
Prenat Diagn 2010; 30: 357–360.
DOI: 10.1002/pd
 THE NATURAL HISTORY OF ANENCEPHALY
RESULTS
Twenty-six cases of isolated anencephaly were identified
in the time period (Figure 1). Median maternal age was
30 years (range 17–41) and 50% were primiparous.
Seven women had a history of previous first trimester
miscarriage, of whom only two were primiparous, and
one was an insulin-dependent diabetic. No other risk
factors were identified. The majority, 65% (17/26),
reported taking folic acid pre-conceptually.
All but one case of anencephaly (25/26; 96%)
was diagnosed prenatally at a median gestation of
21+4 weeks (range 13+4 –32+4 ). The range can be
explained by a number of factors. In four cases the scan
was performed at <11 weeks of gestation and the diag-
nosis of anencephaly was missed. Four women booked
late and their first scan was after 24 weeks of gesta-
tion. In another four cases a scan at 11–14 weeks of
gestation failed to diagnosis anencephaly; these cases
occurred in the first 2 years studied. Finally, one woman
presented late to prenatal care with an intrauterine death
at 32+4 weeks of gestation and anencephaly was diag-
nosed at delivery.
Seven pregnancies (7/26; 27%) developed polyhy-
dramnios and of this group three women required serial
amniodrainage in the third trimester. None of these
women developed pre-eclampsia or had any clinical
signs of maternal mirror syndrome. Three women went
into spontaneous preterm labour at 30–32 weeks of ges-
tation, but this is likely to be related to fetal intrauterine
death in two cases. Six anencephalic (6/26; 23%) fetuses
died in utero at a median gestation of 30 weeks (range
22+4 –32+5 ).
The median gestation at delivery was 35 weeks
(range 22+5 –42+6 ), and 46% (12/26) of fetuses deliv-
ered before 34 weeks. Nine anencephalic fetuses (9/26;
35%) died in utero during labour. Six of the labours
where there was an intrapartum death were origi-
nally induced at a median gestational age of 37 weeks
(32+2 –42+6 ). Only three fetuses were in a breech pre-
sentation in labour. One woman who had two previous
Caesarean deliveries was delivered by Caesarean sec-
tion at 33 weeks. Four vaginal deliveries (4/25; 16%)
were complicated by shoulder dystocia, and advanced
rotational manoeuvres were required to deliver the fetal
trunk. For all labours, the median duration of the first
stage of labour was 4 h, 15 min (range 43 min to 17 h,
25 min) while the median duration of the second stage
was 45 min (range 5 min to 4 h, 40 min).
Sixty-nine percent (18/26) of labours were induced at
a median gestation of 34 weeks (range 22+5 –42+6 ). The
most common indication was maternal request (11/18),
followed by intrauterine death (4/18) and postdates
pregnancy (3/18). In the early part of the time period
under study dinoprostone was the prostaglandin of
choice, whereas latterly misoprostol was used. Median
interval from commencing induction of labour with
prostaglandins to delivery was 32 h (range 10–297).
Fifteen women (15/18; 83%) were delivered within 72 h
of commencing induction. In two cases, induction of
labour at maternal request at 35 weeks of gestation
Copyright  2010 John Wiley & Sons, Ltd.
359
failed; both labours were subsequently successfully
induced at 37 and 40 weeks, respectively.
Eleven infants (11/26; 42%) were alive at birth.
Survival time ranged from 10 min to 8 days (median
survival, 55 min). Twelve infants were female, giving
a slight male preponderance of 1.16 : 1. Six parents
(6/26; 23%) gave consent for neonatal organ donation,
and corneas and heart valves were harvested after
delivery in these cases. There were no maternal postnatal
complications.
DISCUSSION
We report a large series of pregnancies complicated
by fetal anencephaly, where parents chose to continue
the pregnancy. One-fourth of pregnancies were com-
plicated by polyhydramnios and one-fifth of deliveries
by shoulder dystocia. A minority of women laboured
spontaneously preterm, however, many labours were
induced before 38 weeks at maternal request. Anen-
cephalic fetuses were most likely to die after birth, with
23% dying in utero and 35% during labour. Neonatal
survival of up to 8 days was reported.
This study represents the largest cohort of anen-
cephaly cases reported from one clinical service. The
only recent large series reported depended on parental
recollection of clinical experiences and uploading of
these data onto a website, without subsequent review
or verification (Jaquier et al., 2006). Our series is ret-
rospective, but information was directly obtained from
case-notes and other hospital records. In this way, details
of the pregnancies, labour and delivery were accurately
recorded without bias. Another strength of this study is
the detail of onset and stages of labour recorded.
Unlike other studies we do not report a female pre-
ponderance among anencephalic fetuses (James, 1979;
Jaquier et al., 2006). Previous miscarriage was not a
consistent risk factor in these pregnancies (Rushton,
1977). Only a small number of pregnancies laboured
spontaneously preterm, contrary to what has been pre-
viously reported, although the number of inductions
performed before term limits this conclusion. Polyhy-
dramnios was a significant prenatal complication for
one-fourth of our study population, as others have also
found (Jaquier et al., 2006). Many of the women in
our study experienced complications in labour, including
prolonged induction, delay in the second stage or shoul-
der dystocia. This is in keeping with older published
reports of risks of dysfunctional labour and complicated
delivery (Anonymous, 1990), but is at odds with parental
reports of vaginal delivery (Jaquier et al., 2006).
The majority of infants died in utero before or during
labour, in contrast to reports suggesting three-fourths of
anencephalic fetuses are born alive (Jaquier et al., 2006),
but consistent with older statistics which reported that
far more fetuses with anencephaly die before birth than
after (Ford, 2002). However, the majority of intrapartum
deaths in our study occurred in induced rather than
spontaneous labours. Further, although the median inter-
val from commencing prostaglandin induction to deliv-
ery was only 32 h, this does not compare favourably
Prenat Diagn 2010; 30: 357–360.
DOI: 10.1002/pd
360 N. OBEIDI et al.
with evidence from a large series of stillbirths, where
the average induction to delivery interval was 8.5 h
(Wagaarachchi et al., 2002). In this report, 98% of
women were delivered within 72 h of administering
misoprostol, compared to 83% in our study.
It was not the intention of our study to discuss the
ethical and moral issues in the management of pregnan-
cies complicated by anencephaly, but rather to report the
prenatal course, intrapartum obstetric management and
outcome of a large number of cases. Due to the num-
ber of pregnancies where labour was induced prior to
term we cannot report all pregnancies as having a true
spontaneous outcome, and therefore commenting on the
natural history in all of these pregnancies is restricted.
Nonetheless, we believe this information is important
to report, given our almost unique position of routinely
providing prenatal care for continuing pregnancies with
this diagnosis. Our study provides useful information
for health professionals caring for patients with a diag-
nosis of anencephaly, especially in jurisdictions where
continuation of the pregnancy is the minority choice or
where experience may be limited. These findings should
assist in counselling parents appropriately regarding the
complications and the outcome of these pregnancies.
DECLARATION
This article represents original work and has not been
submitted for publication elsewhere. It was presented at
the British Maternal and Fetal Medicine Society annual
meeting in Liverpool in June 2009.
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