Neural Tube Defects and Congenital Hydrocephalus in the

Sultanate of Oman
by A. Rajab,* A. Vaishnav,** N.V. Freeman,** and M.A. Patton***
*Department of Paediatrics, Royal Hospital, Muscat, Sultanate of Oman
**Department of Paediatric Surgery, Royal Hospital, Muscat, Sultanate of Oman
***Department of Medical Genetics, St George's Hospital Medical School, London, UK

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Summary
A retrospective study was carried out in Oman to determine the incidence of neural tube defects
(NTD) and congenital hydrocephalus (CH) and to identify any possible associations. National data
retrieved from hospital records revealed the incidence of NTD in Oman to be comparatively low (1.25
per 1000), but the incidence of CH was much higher than that seen in Western Europe (0.44 per 1000)
and was found to be associated with high rates of other congenital anomalies and neonatal death.
There were no specific environmental factors associated with NTD and high environmental
temperatures during the tropical desert summer (temperatures reach 48°C) were excluded as a
causative factor. In spina biflda families, later born children were more likely to be affected and there
was also an association with increased maternal but not paternal age. Much higher consanguinity
rates were noted in families with NTD and CH than in the general population.

Introduction surgical cases and hospital births were traced back to

Neural tube defects (NTD) are one of the commonest and
most extensively studied congenital malformations.
They were the first of the major congenital malforma-
tions for which primary preventive action has resulted in
a reduction of incidence.'"3 There is evidence that
perioconceptional folic acid can prevent over 50 per cent
Of NTD.4
Patients and Methods
The ascertainment of NTD was based on a retrospective
analysis of hospital records and, in addition, a prospec-
tive cohort was examined in more detail to determine
whether consanguinity, birth order, or parental age
played a significant role in the aetiology of these
abnormalities.
All patients born with NTD and congenital hydro-
cephalus (CH) in Oman are treated in a single paediatric
surgical unit, where computerized data obtained during
1992-1995 were analysed to study associated anoma-
lies, morbidity, and mortality. As children might have
died without surgical treatment and there might be an
underestimate of the true incidence, further data were
collected from all delivery units in the regional hospital
of Oman. These cover over 80 per cent of all deliveries in
the Omani population, and for the period 1989-1995,
delivery records on 242 764 births were examined. All
Correspondence: Dr Michael A. Patlon, Department of Medical
Genetics, St George's Hospital Medical School, Cranmer
Terrace, London SW17 ORE
their place of residence for the purpose of estimation of
population-based incidence, and duplications were
eliminated.
A prospective study on all cases of NTD and CH seen
at the Royal Hospital during 1995 was carried out in
order to determine specific aetiological factors such as
parental age and consanguinity. The parents were
interviewed to obtain a full family pedigree, parental
ages, birth order, a family history of similar disorders, a
maternal history of any illness during pregnancy, and
any occupational exposures.
Statistical analysis of the seasonal variation in the
incidence of NTD was done by the method of Hewitt et
al? The birth order and parental ages were analysed by
the method of Haldane and Smith.6 The effect of
inbreeding was studied by comparing the proportion of
consanguinity within the general population with the
proportion of consanguinity of couples who had given
birth to children with NTD or CH. Tribal names were
also analysed to check for aggregation of abnormalities
within tribes.
Results
Analysis of hospital records and delivery registers
revealed a total incidence of NTD as 1.25 per 1000
births. This total comprised anencephaly (0.69 per 1000),
myelomeningocoele (MMC) (0.45 per 1000), and
encephalocoele (EC) (0.107 per 1000). The total
incidence of CH was 0.53 per 1000 births (Table I),
with a male to female ratio of 1.5:1.
Records were analysed to determine whether there

300 © Oxford University Press 1998 Journal of Tropical Pediatrics Vol.44 October 1998
A. RAJABETAL
TABLE I
Frequency of neural tube defect and congenital hydro-
cephalus in the Sultanate of Oman, 1989-1995
Incidence per 1000
Type of lesion live births
Total NTD 1.25 per 1000
Memngomyelocoele 0.45 per 1000
Anencephaly 0.69 per 1000
Encephalocoele 0.078 per 1000
Meckel-Gruber syndrome 0.029 per 1000
Congenital hydrocephalus 0.44 per 1000
were any associated abnormalities. In one-third of
children with CH who had died, there were associated
congenital abnormalities such as agenesis of corpus
callosum, congenital heart lesions, exomphalos, and
renal agenesis. Since post-mortem examination is not
allowed in Oman for religious reasons, some defects may
not have been detected. Seven cases of encephalocoele
were associated with cystic renal lesions and polydactyly
and were diagnosed retrospectively as Meckel-Gruber
syndrome,7 giving an incidence of this syndrome in
Oman of 0.027 per 1000 births (Table I). The frequency
of associated abnormalities was lower in the other types
of NTD. It is often the presence of additional
abnormalities that is associated with a high mortality;
this was the case in this study. It was found that 51 per
cent of infants with CH died shortly after birth and were
stillborn compared to 7 per cent of cases of myelome-
ningocoele.
In this study it was not possible to look in detail at all
environmental factors, but as maternal heat exposure has
been implicated as a risk factor for NTD8' and the
ambient temperature may be very high in the hot season,
the seasonal variation in the incidence of NTD and CH
was examined by the method of Hewitt et al.5 This
technique revealed no significant seasonal association. In
the 1995 cohort, all 49 interviewed mothers were
housewives and had no history of exposure to chemical
agents or drugs. Diabetes mellitus had been diagnosed in
two and one had leakage of amniotic fluid at 13 weeks of
pregnancy.
Prospective study data included details of interviews
with parents and physical examination of 49 cases (32
MMC, six EC, and 11 CH). The method of Haldane and
Smith6 was used to determine whether there was a
parental age or birth order effect in the cases of MMC.
The birth order, mean and variance in each complete
sibship was determined and no significant paternal age or
birth order effect was demonstrated. Student's Mest was
used to look at maternal and paternal age effects on the
incidence of MMC. Student's / distribution (p < 0.001)
confirmed that the mean age of mothers of MMC cases
(28.95; SD 6.9) was significantly higher than in the
general population (23.23; SD 5.6). This was not so for
mean paternal age (p > 0.1).
Journal of Tropical Pediatrics Vol.44 October 1998
Consanguinity of the affected families studied pro-
spectively was compared with that of the general
population. Consanguinity among parents of 32 MMC
cases was 75 per cent, 44 per cent being first cousins)
compared with 56 per cent in the general population (24
per cent first cousins). All children with CH (11 cases)
came from consanguineous families (45 per cent first
cousins, 27 per cent second cousins, 28 per cent distant
relatives). All six of the EC cases were from first cousin
marriages. Analysis of tribal name in 140 cases of
myelomeningocoele showed the calculated incidence in
tribes to vary from 1 to 2000 to 1 in 7500 deliveries.
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However, there was no striking tribal aggregation or
geographical clustering.
Discussion
The overall incidence of NTD in the Sultanate of Oman
was 1.25 per 1000 in 1989-1995. These figures (Table 2)
are compatible with those of other countries of the Gulf
region10"13 and from the UK.14 Some of the differences
between studies may arise from the method of ascertain-
ment. In our own study there was a difference between
the incidence calculated from surgical data and that from
birth registers; in order to obtain a more accurate figure
we combined the data and excluded duplication.
The incidence of CH was associated with spina bifida
was found to be high (0.44 per 1000 live births)
compared to figures from the UK (0.13 per 1000) and
the US (0.1 per 1000), but may be even higher in some
other Middle Eastern countries (e.g. 0.38 per 1000 in
Iran).13 The delivery register data showed that half of the
babies with CH bom in the capital (51 per cent) died
during the early neonatal period or were stillborn.
Among CH cases treated in the paediatric surgical unit,
57 per cent had major congenital anomalies, which
caused death in 30 per cent. In 16 per cent there was a
history of similar affected relatives. The high male to
female ratio (1.5:1) suggests that some CH cases could
be due to X-linked hydrocephalus. Alternatively, the
greater frequency of consanguinity might suggest a
greater chance of autosomal recessive causes of hydro-
cephalus. More genetic studies with segregation analysis
would be helpful.
In Oman there is a large expatriate population and it is
possible to compare the frequency of congenital
abnormalities with the Omani population with that of
the expatriate population. There were 11 600 births to
expatriates between 1989-1995. In this population the
frequency of myelomeningocoele was similar but the
frequency of CH was three times higher. This suggests
either a genetic difference or a difference in a local
environmental factor.
There was no history of occupational exposure to
noxious agents during pregnancy of mothers giving birth
to children with NTD in Oman. Mercury ingestion has
been implicated in the incidence of NTD in the UK.1
There could be a possibility of greater environmental
exposure, especially in the older, more traditional
301
 A. RAJAB ET AL.

TABLE 2
Incidence of neural tube defects in the Middle East and UK
Anencephaly Spina bifida
Country Period of study No of deliveries studied (per 1000) (per 1000) Overall NTD (per 1000)
18
Kuwait 1988 8913 0.57 0.28 1.19
Kuwait14 1983 36138 1.33
Saudi Arabia" 1987-1990 74923 0.43 0.33 0.82
Bahrain16 1978-1985 88257 1.5
UAE17 1992-1993 16419 0.73
Iran" 1969-1977 13037 0.08 0.54
Jordan38 1991-1993 86812 0.37 1.0 1.63
Scotland20 1988 67000 0.52 0.58 1.10

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Oman (present study) 1989-1995 242 764 0.69 0.45 1.25

mothers, to mercury, lead, antimony, or other substances
which traditionally have been incorporated into local
medicines and cosmetics in Oman.16-17
Analysis of birth order suggested that there is an
increased risk of MMC with older mothers or later born
children. This may be due to a shorter interval between
pregnancies. A higher risk of NTD in larger sibships was
noted in previous studies from British Columbia and
Israel.18' It is still not clear whether the higher
incidence of NTD for multiparous women can be
attributed to dietary folate deficiency, reduced absorp-
tion of folate, an age-related decline in the activity of
enzymes, or a combination of these factors.20'21 Tradi-
tionally, Omani families are large with an average of 6.7
children per family. Planned pregnancies are rare, and
breastfeeding usually continues for 12-18 months and
acts as a natural birth spacing method.
The other explanation for an increased incidence of
NTD in later born children is that there is an increase in
parental age. We found a significant increase in cases of
MMC associated with increased maternal but not
paternal age (p < 0.0001).
Preconceptional folate supplementation is not prac-
ticed routinely in Oman. All expectant mothers receive
5 mg folate daily from the first clinic attendance, which
is usually at the end of the first trimester. At 12 weeks,
multivitamins and iron are added and supplied along
with folate throughout the pregnancy and 12 weeks post-
partum. There is a possibility that folate supplementation
during pregnancy and lactation may help to prevent an
increase in the frequency of NTD in Oman. Smithells
suggested that the use of folate supplements at the end of
one pregnancy can improve the nutritional state of the
next and may reduce the incidence of NTD.3 It may be
possible to reduce the frequency of NTDs further by
promoting a healthy and well balanced periconceptional
diet among women in Oman.
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