PATTERNS OF NEURAL TUBE DEFECTS AT TWO TEACHING HOSPITALS IN ADDIS ABABA, ETHIOPIA A THREE YEARS RETROSPECTIVE STUDY

Abstract

Background: Neural tube defects (NTDs), one of the most common congenital malformations, are potentially preventable cause of perinatal morbidity and mortality. Objectives: To give baseline description of NTDs and their outcome at two teaching hospitals in Addis Ababa, Ethiopia. Materials and Methods: A retrospective cross sectional descriptive study conducted from September 2009 to August 2012. Results: During the study period out of 28,961 deliveries 177 cases of NTDs were identified, giving an overall NTD prevalence of 6.1/1000. Only 12% (21/177) were diagnosed before 28 weeks of gestation. The mean gesta-tional age at diagnosis of NTDs was 33.8 weeks (±5.5). Majority, 93.2% (165/177), had antenatal care (ANC) follow up. Most, 72% (127/177), were diagnosed by ultrasound before delivery while 28% (50/177) were identified at the time of delivery or expulsion. Majority, 85.3% (151/177), never received folic acid supplementation. Only less than 1% (2/177) of the mothers started taking folic acid supplementation pre-conceptionally. Only a third, 33.3% (59/177), of the fetuses were born alive while only 13.6% (24/177) were discharged alive. Myelomeningocele, identified in 51.4% (91/177), was the commonest NTD in this study. Conclusion and recommendations: The proportion of NTDs in this study is among the highest globally reported rates. The practice of periconceptional folic acid supplementation is negligible. And although most had ANC follow up the vast majority of NTDs were diagnosed late in the third trimester. It is, therefore, highly recommended to consider implementing national preventive strategies to reduce the prevalence of NTDs in Ethiopia.

Full text

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Gemechu Sorri, Eyasu Mesfin, Ethiop Med J, 2015, Vol. 53, No. 3
ORIGINAL ARTICLE
PATTERNS OF NEURAL TUBE DEFECTS AT TWO TEACHING HOSPITALS IN
ADDIS ABABA, ETHIOPIA A THREE YEARS RETROSPECTIVE STUDY
Gemechu Sorri, MD1 Eyasu Mesfin, MD1
ABSTRACT
Background: Neural tube defects (NTDs), one of the most common congenital malformations, are potentially pre-
ventable cause of perinatal morbidity and mortality.
Objectives: TogivebaselinedescriptionofNTDsandtheiroutcomeattwoteachinghospitalsinAddisAbaba,
Ethiopia.
Materials and Methods: A retrospective cross sectional descriptive study conducted from September 2009 to Au-
gust 2012.
Results: During the study period out of 28,961 deliveries 177 cases of NTDs were identified, giving an overall
NTD prevalence of 6.1/1000. Only 12% (21/177) were diagnosed before 28 weeks of gestation. The mean gesta-
tional age at diagnosis of NTDs was 33.8 weeks (±5.5). Majority, 93.2% (165/177), had antenatal care (ANC) fol-
low-up. Most, 72% (127/177), were diagnosed by ultrasound before delivery while 28% (50/177) were identified at
the time of delivery or expulsion. Majority, 85.3% (151/177), never received folic acid supplementation. Only less
than 1% (2/177) of the mothers started taking folic acid supplementation pre-conceptionally. Only a third, 33.3%
(59/177), of the fetuses were born alive while only 13.6% (24/177) were discharged alive. Myelomeningocele,
identified in 51.4% (91/177), was the commonest NTD in this study.
Conclusion and recommendations: The proportion of NTDs in this study is among the highest globally reported
rates. The practice of periconceptional folic acid supplementation is negligible. And although most had ANC fol-
low-up the vast majority of NTDs were diagnosed late in the third trimester. It is, therefore, highly recommended
to consider implementing national preventive strategies to reduce the prevalence of NTDs in Ethiopia.
Key words: NTD, Myelomeningocele, Spina Bifida
1Department of Obstetrics & Gynecology, School of Medicine, AAU, Addis Ababa
INTRODUCTION
Neural tube defects (NTDs) are a group of severe
human congenital malformations caused by the de-
fective closure of neural tube between 21 to 28 days
following conception. They represent one of the most
common congenital malformations in neonates
worldwide (1). NTDs can be classified as open or
closed, depending on whether neural tissues are ex-
posed or covered by skin, respectively. Open NTD
are more frequent and include spina bifida
(myelomeningocele), anencephaly, encephalocele,
hydranencephaly, iniencephaly and schizencephaly
(2).
The worldwide prevalence of NTDs ranged from 1 to
10 per 1000 (3). Each year, 300,000 to 400,000 in-
fants worldwide are born with NTDs including spina
bifida and anencephaly (4). They remain an impor-
tant yet potentially preventable cause of perinatal
morbidity and mortality. The risk of death is depend-
ant on the severity of the lesion and on other factors
such as the availability of medical and surgical re-
sources (5). All anencephalic children are stillborn or
die soon after birth. Children with meningocele and
myelomeningocele have higher survival rates, gener-
ally due to extensive medical care and surgery.
The exact cause of NTDs is not known. The aetiol-
ogy, however, includes both genetic and environ-
mental factors. Maternal socioeconomic status, geo-
graphic area, occupational exposure, maternal use of
antiepileptic drugs, education, and maternal nutrient

120
deficiency have been associated with variations in
the incidence (6,7). The best known risk factor for
foetal NTD is maternal folate deficiency (8, 9). And,
screening tests for NTDs include ultrasound exami-
nation and measurement of Maternal Serum Alpha-
Fetoprotein (MSAFP) at 16–18 weeks of gestation
(10). Screening decreases morbidity and mortality by
promoting access to earlier diagnosis, enabling fami-
lies to make informed reproductive choices, and de-
signing appropriate strategies for prenatal care and
delivery.
Prenatal maternal screening programs with termina-
tion of affected pregnancies combined with pericon-
ceptional folic acid supplementation and food fortifi-
cation have led to a decrease in the prevalence of
NTDs where these interventions are practiced (11-
17). For example, the incidence of NTDs in England
and Wales declined by 96 percent between 1970 and
1997: from approximately 3.2 per 1000 births to 0.1
per 1000 births (13). Forty percent of the decline was
attributed to antenatal screening with termination of
affected pregnancies and 56 percent was attributed to
a decline in incidence, due at least in part to an in-
crease in dietary folate intake. In addition, random-
ized trials have consistently shown peri-conception
folic acid supplementation to be one of the public
health interventions effective in reducing the risk of
NTDs (12,18). Data from randomized trials also indi-
cate that periconceptional folic acid supplementation
reduces the risk of recurrent NTDs by about 70 per-
cent (19).
Published data on NTDs in Ethiopia is very limited.
One retrospective review of 115 children with neural
tube defect (NTD) conducted from January, 2001 to
June 2005 at Ethio Swedish Children's Hospital at
Tikur Anbessa Hospital showed the most common
defect seen to be myelomeningocele (64.4%); fol-
lowed by meningocele (18.3%) and encephalocele
(13.0%). Associated anomalies like clubfoot un-
descended testis, different types of hernias, hydro-
celes etc. were noted in 28.7% of the patients (20).
Neurosurgical service provided in Ethiopia is also
very limited. A local study done in neurosurgical
department on pediatric patients awaiting admission
to Tikur Anbessa Hospital (TAH) from July 2006-
February 2007 demonstrated that there were 338
children in waiting lists out of which 41% were mye-
lomenigeocele and 29% were hydrocephalus. In ad-
dition, the average waiting time for admission was
447 days and the patients had to travel 300 miles on
average as most of them come from rural part of
Ethiopia (21).
Neither routine supplementation of folic acid for
women of reproductive age group nor routine screen-
ing for NTDs is practiced in the country. This study
was conducted at two teaching hospitals in Addis
Ababa, Ethiopia. And it is designed primarily to give
a baseline description of neural tube defects and their
outcome in our setup.
MATERIALS AND METHODS
This is a hospital based cross sectional descriptive
study done from September, 2009 to August, 2012 at
Tikur Anbessa Hospital (TAH) and Gandhi Memo-
rial Hospital (GMH), Addis Ababa, Ethiopia. It was
done through a retrospective review of charts of all
mothers who were admitted to the two teaching hos-
pitals and delivered or aborted a fetus with NTD.
Their Medical Record Numbers (MRN) identified
from admission log books in the maternity ward and
Neonatal Intensive Care Unit (ICU) were used to
retrieve medical records/charts. Data was collected
by the investigator using a pre-tested questionnaire
from medical records of the study participants. The
collected data was coded, cleaned and analyzed using
SPSS version 20 statistical software. Summary tables
and charts were used for describing data.
Ethical clearance was obtained from the research and
publication committee of the department of Obstet-
rics & Gynecology, and IRB of Addis Ababa Univer-
sity. Permission was also obtained from the Hospitals
to access the medical records of mothers included in
the study.
RESULT
During the study period there were a total of 28,961
deliveries in the two teaching hospitals. And, a total
of 177 mothers the outcome of whose pregnancies
was complicated with NTDs were identified. The
overall occurrence of NTDs in this study, hence, was
6.1/1000 births (live birth and fetal deaths). The
mean and median ages of the participant mothers
were 27.1 (±5.6) and 27 (IQR 7) respectively. Major-
ity were house wives and from Addis Ababa with
proportions of 48.6% (86/177) and 77.4% (137/177)
respectively. ( Table 1)

121
Table 1: Socio-demographic characteristics of mothers whose pregnancy outcome was complicated with NTDs
at twoteachinghospitals,AddisAbaba,Ethiopia,2009‐12.
Characteristics Frequency Percentage (n=177)
Address Addis Ababa 137 77.4 %
Out of Addis Ababa 40 22.6 %
Marital Status Married 163 92.1 %
Divorced 1 0.6 %
Single 13 7.3 %
Occupation House Wife 86 48.6 %
Governmental Employee 27 15.2 %
Private Employee 21 11.9 %
Factory worker 15 8.5 %
Student 14 7.9 %
Others 14 7.9 %
Primigravidity and gravida II were the commonest
gravidities each accounting for 43.5% (77/177) and
32% (57/177) respectively. The mean gravidity was
2±1.2 while the median gravidity was 2 (IQR = 2).
Only 12% (21/177) of the cases were diagnosed be-
fore 28 weeks of gestation. The mean gestational age
at diagnosis of NTDs was 33.8 weeks (±5.5). Majority
of the mothers, 93.2% (165/177), had ANC follow up.
The ANC follow up in 72.3% (128/177), 13%
(23/177) and 8% (14/177) of the mothers was in a
health center, private clinic and hospitals respectively.
Most of the NTDs, 72% (127/177), were diagnosed by
ultrasound before delivery while 28% (50/177) of
cases were identified at the time of delivery or expul-
sion. Majority, 85.3% (151/177), never received folic
acid supplementation throughout the entire pregnancy.
Only less than 1% (2/177) of the mothers started tak-
ing folic acid supplementation pre-conceptionally.
The rest, 3.4% (6/177) and 10.2% (18/177), of the
mothers received folic acid in the first and after first
trimesters respectively. (Table -2 ).
Medical illnesses were identified in 12.4% (22/177) of
the study participants. Hypertension, identified in
3.4% (6/177) of the mothers, was the commonest
medical illness, and diabetes, epilepsy and others were
found in 2.3% (4/177), 1.7% (3/177) and 4.5% of the
mothers respectively. The mode of delivery in about
74% (131/177) of the study participants was spontane-
ous vaginal. Cesarean section and laparatomy for uter-
ine rupture were done in 17.5% (31/177) and
0.1% (2/177) of the cases respectively. The rest, 7.3
% (13/177), were terminated medically. The indica-
tions for the cesarean sections were malpresentation
due to breech and transverse lie, previous C/S scar and
CPD in 48.5% (16/33), 18% (6/33) and 27% (9/33) of
the cesarean deliveries respectively. The diagnosis of
congenial malformation was made after delivery in
39% (12/31) of the mothers who delivered by cesar-
ean section.
Perinatal outcome: Majority of the neonates born to
the study subjects were females accounting for 72.3%
(128/177) with male to female ratio of 1:2.6. (Table 1)
Only a third, 33.3% (59/177), of the fetuses were born
alive while the rest 66.7% (118/177) were still born.
The mean birth weight was 1991 gm±951gm while
the median weight was 1900 gm (IQR=1650gm). Out
of the 59 live born neonates 40 (67.8%) had 1st minute
APGAR score of <6 whereas 19 (32.2%) had APGAR
score of >6. Death within few minutes of delivery and
before referral to Neonatal Intensive Care Unit
(NICU) occurred in 28.8% (17/59) of the live born
neonates. The rest, 71.2% (42/59) of the live born
neonates, were referred to NICU. Fifteen, 35.7%
(15/42), of the referred neonates died in the early neo-
natal period while in the NICU with the mean time of
death of 6.8 hrs. Only 12.3% (24/59) of the live born
neonates or 13.6% (24/177) of the total fetuses born or
expelled were discharged alive with appointment to
neurosurgical unit. The outcome of the admission was
not documented for three of the admitted cases. (Table
3)

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Table -2: Obstetric characteristics of mothers whose pregnancy outcome was complicated with NTDs
at twoteachinghospitals,AddisAbaba,Ethiopia,2009‐2012. (n=177)
Characteristics Frequency Percentage, % (n=177)
Gravidity
I 77 43.5
II 57 32.2
III 24 13.6
IV 10 5.6
V 6 3.4
VI 3 1.7
GA at diagnosis of NTD
(n=177)
< 28 weeks 21 12
≥ 28 weeks 156 88
ANC follow up (n=177)
Yes
At health centre 128 72.2
At Hospital 23 13
At private facility 14 8
Sub total 165 93.2
No 12 6.8
Mode of NTD diagnosis
Ultrasound before delivery 127 72%
Identified after delivery/
expulsion
50 28%
Received folic acid supplemen-
tation
Yes
Preconception 2 1.1
During first trimester 6 3.4
After first trimester 18 10.2
Subtotal 26 14.7
No 151 85.3

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Table 3: Perinatal outcome of mothers whose pregnancy was complicated with NTDs at two
TeachingHospitals,AddisAbaba,Ethiopia,2013. (n=177)
Characteristics Frequency Percentage, (n=177)
Sex
Male 49 27.7
Female 128 72.3
Pregnancy outcome at the time of delivery
Alive 59 33.3
Dead (Stillborn) 118 66.7
Pregnancy outcome at discharge
Alive 24 13.6
Dead
Still born 118 66.7
Death within few minutes of delivery
and before referral to NICU
17
9.6
Death after referral to NICU 15 8.5
Sub total 150 84.7
Unknown 3 1.7
Myelomeningocele, identified in 51.4% (91/177) of
the cases, was the commonest NTD in this study.
Anencephaly, encephalocele and meningeocele were
also the NTDs identified in 43.5% (77/177), 2.8%
(5/177) and 2.2% (4/177) of the neonates respec-
tively. Other associated congenital anomalies were
observed in 51.8% (92/177) of the neonates. The
most common associated anomaly observed was hy-
drocephalus identified in 37.8% (67/177).
The other associated anomalies include club foot and
gastrointestinal anomalies (omephalocele, gastroche-
sis, imperforated anus and diaphragmatic hernia)
identified in 6.8% (12/177) and 3.9% (7/177) neo-
nates respectively. (Table -4 )
Maternal post partum complications were identified
in 21(11.9%) of the mothers. These complications
include PPH secondary to uterine atony, uterine rup-
ture secondary to obstructed labor due to hydro-
cephalus and genital laceration occurring in 7 (4%),
2 (1.1%) and 12 (6.8%) of the mothers respectively.

124
Table 4: NTD type and associated anomalies identified in mothers whose pregnancy outcome
was complicated with NTDs at twoteachinghospitals,AddisAbaba,Ethiopia,2009‐2012. (n=177)
Characteristics Frequency Percentage, (n=177)
Type of NTD identified
Myelomeningocele 91 51.4
Anencephaly 77 43.5
Encephalocele 5 2.8
Meningeocele 4 2.2
Associated congenital anomaly (n=177)
Yes
Hydrocephalus 67 37.8
Club foot 12 6.8
GI anomalies 7 3.9
Cleft lip 2 1.1
Others 4 2.2
Sub total 92 52
No 85 48
DISCUSSION
One of the Millennium Development Goals initiated
by the United Nations was dedicated to reducing
global child mortality rates. Since 1990, global child
mortality has been declining largely due to the focus
on communicable diseases (22). This reduction of
mortality has led to the neglected causes of child
mortality to be exposed, including that of congenital
abnormalities (23). Neural tube defects (NTDs) are
one of the most common major birth defects second
in frequency only to congenital heart diseases (24).
The incidence of NTDs varies according to the geo-
graphic conditions, race, sex of the baby and certain
maternal conditions (25).
In most developed countries and many developing
countries like South Africa the incidence is less than
1/1000 mainly as a result of fortification of their diet
with folic acid and perinatal supplementation of folic
acid. Regardless of the progress in control of NTDs
observed in these countries, NTD continue to be a
problem of significant public health impact in our
setup. In this study the overall prevalence of NTDs
was found to be 6.1/1000 deliveries.This prevalence
of NTDs in this study (6.1/1000) is 5 and 9 times
higher than reports from South Africa (1.4/1000) and
Thailand (0.67 /1,000 births) respectively.
Only 15% of mothers were seen to have been supple-
mented with folic acid, 69% of which received the
supplementation in the third trimester when it has no
protective effect. This could be due to lack of knowl-
edge of the importance of folic acid in reducing the
prevention of NTDs by the mothers as well as health
care providers (26). This is in agreement to a prior
study done by Mohammed at Jigjiga University Hos-
pital on supplement use among pregnant women in
Ethiopia, in which 76.4% women claimed no aware-
ness about the benefits of early supplementation and
particularly folic acid intake was found to be negligi-
ble during the prenatal as well as antenatal period
(27).
The most common type of NTD observed in this
study was myelomeningocele 91(51.4%) followed by
anencephaly 77(43.5%). This finding is in agreement
with most other international studies (28-31). Similar
study done at Tikur Anbessa Ethio-Sewdish Hospital
and published in 2009 found the most common

125
anomaly to have been myelomeningocele (64.4%)
and meningocele 18.3 % (20). The study, however,
was conducted in NICU where only live neonates
were referred leading to higher proportion of alive
spina bifida which had better prognosis while exclud-
ing anencephalic babies which die soon after deliv-
ery.
NTDs were observed to occur more commonly in
females in our study with male to female ratio of
1:2.6 which is comparable to reports from many
countries. A case-control study based on the Oxford
Record Linkage about 70 percent of the children with
anencephaly and 60 percent of the children with
spina bifida were females (32). The sex distribution
in the Thailand 10 years review, however, was equal
among NTD cases with 55 (48%) females, 59 (51%)
males and one (1%) unidentified sex (29).
Although 95% of mothers whose pregnancy outcome
complicated by NTDs had ANC follow-up only 12%
of them were diagnosed before 28 weeks of gestation
and the mean gestational age at the time of diagnosis
was 33.9 week ±5.6 weeks. This clearly shows the
failure of the ANC service in our setup to timely di-
agnose NTDs. Detecting lethal congenital anomalies
early and termination in the first trimester could have
avoided caring anomalous fetus to third trimester of
pregnancy and complications associated with late
termination. This problem would have been reduced
by screening all mothers in the second trimester with
ultrasound and determining MSAFP as demonstrated
in high income countries where the prevalence was
reduced by 56% just by screening and terminating
the affected fetus (13).
Limitations of the study: As this study is retrospec-
tive and the study population not representative of
the general population the study findings may not
reflect the national situation.
Conclusion and recommendations: In conclusion,
the prevalence of neural tube defects in this study is
among the highest globally reported rates the most
prevalent NTD being myelomeningocele. The prac-
tice of periconceptional folic acid supplementation in
our setup is negligible. And although most had ANC
follow-up the vast majority of NTDs were diagnosed
late in the third trimester.
Considering the findings of this study and cost of
treatment of NTDs it is highly recommended to con-
sider implementing national preventive strategy to
reduce the prevalence of NTDs in Ethiopia. And
based on lessons learned from other countries; early
screening and periconceptional folic acid supplemen-
tation are the two effective possible approaches to
bring about the required reduction in NTD preva-
lence in the country.
In addition, further large scale prospective studies are
needed to have reliable estimates on burden of
NTDs, associated factors and cost benefit analysis of
screening and preconception folic acid administration
for Ethiopian set-up.
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