Objectives : To find out the relative prevalence of fetal neural tube defect (NTD) and its outcome in terms of survival at birth and beyond 2 years of age.
Methods : A 10-year prospective (2008–2018) observational study was performed, which included all prenatally detected fetal NTD. Two-year follow-up was done in cases of pregnancies resulting in live birth, in terms of their survival, physical morbidity and developmental delay.
Results NTD was seen in 401/648 (62%) cases among the central nervous system malformations. More than half of the cases (54.1%) presented after 20 weeks of gestation, and 42.8% of the mothers were primiparous. Spina bifida was seen in 206 cases, anencephaly in 144, encephalocele in 43, whereas iniencephaly was seen in only eight cases. Associated anomalies were present in 51.2%. Only 19.0% cases were live-born, and merely 11% were alive beyond 2 years of age. Among types of spina bifida, lumbosacral meningomyocele was the most common (41.6%), whereas thoracic was the rarest (8.7%). After 2 years, physical disability was observed in more than half of the cases who survived.
Conclusions: NTD is one of the commonest malformations with high mortality, and the physical and mental sub-normality is high among those who survive.
Keywords Fetal hydrocephalus · Central nervous system anomaly · India · Survival after birth · Spina bifida · Anencephaly · Encephalocele
The central nervous system anomalies are the most frequently
antenatally detected malformations, and the neural
tube defects (NTDs) are the commonest among them [1].
Although the incidence of spinal dysraphism has significantly
decreased over the last few decades, the incidence is
still high in countries with poor socioeconomic status [2–4].
Neural tube defects affect 0.6 per 1000 live births in the USA
and 0.5–2 per 1000 pregnancies worldwide [4]. The etiology
of neural tube defects is multifactorial and can be attributed
to genetic predisposition, vitamin deficiencies or teratogen
exposure. Of these, low levels of folate in the maternal
blood prior to conception have been implicated as the most
important cause [3]. Unfortunately, poor awareness regarding
folate supplementation and the high rate of unplanned
pregnancy has led to underutilization of this preventive strategy,
especially in low-resource settings [5].
In 1972, John Lorber published a controversial paper
describing the bleak outcome of a cohort of children born with myelomeningocele [6]. He opined that the babies with
clinical features suggestive of poor prognostic significance
should not be offered active treatment. Instead, he suggested
that efforts should be directed to those who are most likely
to benefit in the long term [6]. Over the subsequent 46 years,
the outlook for the children born with myelomeningocele
has changed in the developed nations, but it is virtually the
same in the developing countries. Since there is no study
on the outcome of cases in the existing environment, it is
difficult to provide realistic counseling to the couple after
its prenatal diagnosis.
There is paucity of data on the outcome of NTD in the
developing countries which has limited health care infrastructure
and a high infant mortality rate, leaving little hope
for proper care and management of children with NTDs.
The problem is compounded in India as the abortion law,
also known as medical termination of pregnancy (MTP) act,
does not allow termination of pregnancy with fetal anomalies
after 20 weeks of gestation, leaving its continuation as
the only option if an NTD is diagnosed after 20 weeks.
The counseling requires information regarding the outcome
not only at birth but subsequently also. The parents
need to be informed about the associated physical and mental
morbidity, need for surgery and impairment after surgery.
The data from the developed nations are not suitable
for counseling regarding the postnatal outcome in a lowresource
set up. Thus, indigenous data on outcome in the
existing setup are warranted for realistic counseling.
The aim of the study was to find out the relative prevalence
of different types of fetal neural tube defects and its
outcome in terms of survival at birth and at 2 years.
It was a prospective study, performed after ethical clearance.
It included all cases of antenatally detected fetal NTDs
referred to the fetal medicine clinic in the last 8 years of the
10-year study period (2008–2018). Mothers were included
in the study after consents. Any defect in the closure of the
spinal cord and vertebral column or skull vault was termed
as NTD. Cases presented as spinal defects in the form of
meningomyocele or spinal diastematomyelia, seen in the
axial and coronal sections on ultrasound. Anencephaly was
easy to detect with findings suggestive of the absence of
skull vault and protruding eyeballs. Encephalocele was protrusion
of cystic mass from a defect in the skull vault, while
iniencephaly was extension of fetal head with fusion of the
cervical vertebra.
After reaching a diagnosis, the mothers underwent targeted
scanning to rule out other congenital malformations.
When the diagnosis of major fetal anomalies was confirmed
at or before 20-week gestation, termination of pregnancy was offered. If the couple desired continuation of pregnancy
or when the gestational age was more than 20 weeks, genetic
and pediatric surgery consultation was taken. Repeat ultrasound
examinations were carried out to follow the evolution
of the anomaly. All subjects were delivered at the institution.
Mothers who did not deliver at our hospital were considered
lost to follow-up.
The pediatrician was informed about the fetal condition
at the time of delivery, so that necessary arrangement for
immediate postnatal management could be planned. All
live-born babies underwent appropriate tests. All cases
requiring surgical intervention were referred to specialized
departments for further management. Surgery for repair of
meningomyocele, shunting procedure and orthopedic foot
correction was done as per the requirement and availability
of facilities. Pediatric examination records were maintained,
and telephone interviews were conducted to track
the outcome of children till 2 years of age. The outcome
of babies in terms of survival and physical morbidity such
as poor bladder control, limb abnormalities requiring additional
medical attention, was asked for. The questionnaire
concerning the developmental milestones achieved within
the expected time period was also enquired for. Whether the
baby underwent any surgery was also sought.
In the first 8 years of study period, there were 102,216
deliveries, of which the central nervous system defects were
observed in 694 cases antenatally. Out of the 648 fully followed
cases of CNS defects, 401 could be attributed to NTD;
42 cases of NTD were lost to follow-up. Among the NTD
cases, spina bifida was the most common (51.4%), followed
by anencephaly (35.9%), encephalocele (10.7%) and iniencephaly
in the rest (2.0%).
The antenatal profile of the mothers is shown in Table 1.
The mean age of the mothers included in the study was
25.1 ± 3.67 years. Most of them were young and primiparous
(42.8%). Of all the subjects, 84 (20.8%) had an obstetric
history of one or more previous abortions. The mean gestational
age at the time of presentation was 26.3 ± 8.3 weeks.
In more than half of the cases (245/401, 61.1%), the women
presented after 20 weeks of gestation.
The details of the delivery are given in Table 2. The mean
gestational age at delivery was 29.4 ± 7.5 (11–42 weeks).
The incidence of cesarean section was as low as 6.7%. The
ratio of male/female was 1: 2 in anencephaly, whereas it was
1:1 in the rest. Associated defects were observed in over half
of the cases (51.2%). Talipes equinovarus (TEV) was seen
in 127 cases, hydrocephalus in 97 cases, omphalocele and
other abdominal wall defects in 16 cases, cleft lip and palate
in nine cases, and ambiguous genitalia was observed in three cases. Syndromic association was observed in seven cases
of encephalocele, they were Meckel–Gruber syndrome in
three cases (Fig. 1), Joubert syndrome in one (Fig. 2), and amniotic band disruption sequence in three cases (Fig. 3).
Karyotyping was performed in 18 cases with multiple
defects, which was found to be abnormal in two (trisomy
18, unbalanced translocation).
Among 156 cases which presented at or before 20 weeks,
all except two opted for termination of pregnancy (154/401,
38.4%). One could be attributed to religious reasons and
the other to the history of previous three abortions preceding
the present precious pregnancy. Of the 401 pregnancies,
171 (42.6%) resulted in stillbirth (Table 2). Among these
stillbirths, 78 (19.5%) were ascribed to spina bifida and 13
(1.2%) to encephalocele.
Only 76/401 (19%) pregnancies constituting spina bifida
and encephalocele cases resulted in live birth. The followup
of the cases with spina bifida and encephalocele is given
in Table 3. Among those with spina bifida, the defect in
the lumbar/sacral region was the most common (41.6%)
followed by the thoracic/cervical region (8.7%). Anterior
encephalocele was seen in only three cases and was posterior
in the rest 40 (10%).
On assessment of the survival of the live-born babies,
it was found that 24/62 live-born with spina bifida died in
the subsequent 2 years, and only 38/401 (9.4%) were alive
after 2 years. Among the subjects with encephalocele, 6/401
(1.5%) survived beyond 2 years. At the end of 2 years,
44/401 (11.1%) babies were alive, of which 29/401 (7.2%)
had physical disability and 16/401 (3.7%) had developmental
delay. Surgery was performed in all cases with meningomyocele
or encephalocele, but was not performed in spina
bifida occulta and in two cases of encephalocele. Only
15 children (1.3%) had no mental or physical impairment
(Table 3).
Table 4 shows the outcome of 42 cases of spina bifida who
underwent surgery; 35 of them were alive after 2 years. Most
of the cases underwent surgery at 2–3 months (22/42) and
the rest after 6 months to 1 year of age. The timing of surgery
depended upon the availability of dates by the neurosurgeon
and was often delayed. Meningomyocele repair was done in
all, and shunting procedure for hydrocephalus was also done in 13 cases. Among the complications of the procedure, in 10/42
cases there was infection in the operated site and in 7/42 cases
there was death in the postoperative period. Bowel and bladder
incontinence was noticed in 25/35 live cases, and there was no
residual defect in 10/35 live cases. Follow-up was at 6 monthly
interval for most of the cases (18/35 cases) (Table 4).
The present study provides the relative prevalence of NTD
cases from a tertiary referral center of a populous developing
country and acquaints us to the magnitude of the problem.
The majority of the mothers in the study were at low risk.
In more than half of the cases, the abnormality was detected
in the latter half of pregnancy. Only one-fifth of the babies
were delivered live. After 2 years, just over half of them
were live. Surgical intervention was provided in all surviving
cases; however, in most of the cases it was delayed due
to lack of resources, therefore resulting in poorer outcome
in two-third of the cases.
The incidence of NTDs is 2.79/1000 births in India [7];
it was estimated to be 3.9/1000 births in the present study.
In our study, over half of the cases had spina bifida, and
one-third of them had anencephaly. Similarly, in a study
from Nigeria, 64% of cases had spinal lesions, all of which
were in the lumbosacral region [8]. Associated anomalies
were present in more than 50% cases, and hydrocephalus
was most common; it was found to be associated in 58.8%
of the children with NTD in the study by Kumar et al. [9].
Only 19% of the babies were delivered live. The probable
reason for high number of stillbirths was that, in cases with
associated severe hydrocephalus, cephalocentesis was done
for allowing vaginal delivery, as consent for cesarean section
was not given. It was due to the same reason that vaginal
delivery was preferred even for cases with fetal distress in
labor. Within 2 years, nearly one-third (24/62) among the
live-born cases with spina bifida died. The physical disability
was present in almost two-third of the surviving cases
(25/38) with spina bifida. Many previous studies have also
shown that most of the children who survive have multiple
system involvement, severe handicap and a limited life
expectancy [2, 10, 11].
Among those with spina bifida, only 20.4% could undergo
surgery; no case was operated in the first month of life. Surgical
intervention was delayed in most of the cases due to
lack of resources. Infection was a common complication;
urinary or fecal incontinence was present even after surgery
in 25/35 cases who underwent surgery. In the previous study
by Kuo et al., it was concluded that the delay in care was an
important aspect of health care quality. The patients who
suffered adverse effects following neurosurgical procedures
were more likely to have had a delay in surgery [12]. In an
earlier study by Shin et al., higher cervicothoracic lesions
were found to be associated with a lower survival than for
lumbosacral, and in the present study, none of the cases with
thoracic lesions survived after 2 years [13]. In Lorber’s original
series, 75 of 200 (37.5%) died in the first year of life [6].
In a study by Hunt et al., the rate of mortality at the first year
was 25 of 117 (21%) [14]. In the present study, nearly half of
the babies with physical morbidity also had developmental
delay and only 15/401 (3.7%) had minimal of no disability.
The limitations of the study were the lack of details
regarding the objective absence of folic acid deficiency. The
root cause of NTD is folic acid deficiency, and the fortification
of food with FA and awareness among women regarding intake of FA prior to conception is necessary as it can be
prevented with proper nutritional folic acid intake. Another
major limitation was that the follow-up was questionnaire
based and neurological examination of the babies was not
done. Other weakness could be the follow-up of only 2 years,
though the increase in the length of the follow-up could have
increased the possibility of confounding variables like the
environmental factors to bias the results. The strength of
the study was the large cohort of cases with NTDs from a
developing country and postnatal follow-up of cases till the
period of 2 years.
The present study throws light on the outcome of cases of neural tube defects, not only at birth but at the end of 2 years. The findings show that their outcome in the present study situation is rather grim and far from the outcome data provided in literature from developed nations. Thus, the data regarding its outcome are helpful in providing realistic counseling to the couple. It also stresses upon the need for preventive measures such as periconceptional folic acid and about policy regarding ultrasound before 20 weeks of pregnancy, considering amendment of the termination of pregnancy law, and furthermore, the need for improving facilities for surgery in children with such defects.
Conflict of interest There is no conflict of interest among authors.
Ethical Approval The research involves human participants, and ethical
clearance has been taken from institute’s ethical committee.
Informed Consent Informed consent was taken from the participants
before conduction of the study.