Key-words:
Meningomyelocele - neonate - neural tube defect
Introduction
Neural tube defects (NTDs) are a heterogeneous and complex group of congenital central
nervous system (CNS) anomalies. Anencephaly, spina bifida, and encephalocele are included
in this group. Inadequate cranial extension of the notochord which is constituted
by the midline mesoderm, inadequate neurulation, lack of separation of the skin, and
neural ectoderms after neurulation is completed and problems occurring during the
process which constitutes filum terminale all cause open or closed spinal dysraphism.[[1]] Encephalocele forms after the neural tube are closed.[[2]] Neural malformations and malformations of the other organ systems frequently accompany
NTDs.[[3]],[[4]]
In patients with lumbosacral spina bifida, problems including motor and sensory dysfunction
in the lower extremities, anal and urethral sphincter failure, and neurogenic bladder
may be observed. Especially, most patients with thoracic and lumbosacral spina bifida
have an increased probability of hydrocephaly and Arnold–Chiari type 2 (hydrocephaly
in association with meningomyelocele) malformation.[[5]],[[6]] Treatment and follow-up of patients with NTD require collaboration of many branches
of health care and cause significant healthcare expenses.[[7]] Generally, these congenital malformations significantly increase the rate of mortality
and disability in the neonatal period and the 1st year of life.[[8]]
This study was performed to retrospectively examine the clinical courses in patients
hospitalized in the neonatal intensive care unit (NICU) in our hospital because of
NTD.
Materials and Methods
Babies with NTD were specified by examining the records of the babies hospitalized
in Baskent University Istanbul hospital in the last 5 years (October 2013–August 2018).
File records of all 69 babies who were found to have NTD could be reached. Gender,
birth weight, gestational age at the time of birth, maternal age, use of folic acid
and medication during pregnancy, hypertension, diabetes and other maternal diseases,
prenatal ultrasonography findings, time of prenatal diagnosis of NTD, familial history
of morbidity, consanguinity between the mother and father, localization of spina bifida,
if the sac was perforated, lower extremity examination findings, accompanying anomalies
and comorbidities, ultrasonography findings, computed tomography findings or magnetic
resonance imaging (MRI) findings, treatments applied, follow-up times, and reasons
for mortality in the ones who died were recorded. SPSS statistical software (SPSS
11.5, SPSS Science, Chicago, IL, USA) program was used for statistical analyses. This
study was approved by Baskent University Medicine and Health Sciences Research Committee
(Project Number: KA18/297).
Results
The clinical characteristics of the subjects are summarized in [[Table 1]]. Thirty-eight (55.1%) of the babies were female and 31 (44.9%) were male. The median
birth weight was 3150 (2640–3450) g, the median gestational week at the time of birth
was 38 (37–39) weeks, and the median maternal age was 27 (22–33) years.
Table 1: Clinical characteristics of the subjects
While a history of periconceptional use of folic acid was found in 10 (25%) mothers,
30 (75%) mothers did never use folic acid during pregnancy. Only two of the mothers
(5%) used Vitamin B12. Information related to use of folic acid and Vitamin B12 could
not be reached for 29 mothers. Four mothers (5.7%) were found to have a history of
drug usage during pregnancy. One mother used selective serotonin reuptake inhibitor
because of depression from the first trimester, one mother used alpha methyldopa because
of gestational hypertension in the second and third trimester, and two mothers used
antibiotics the names of which they could not remember, because of infection.
In the morbidity history of the mothers, one mother had gestational hypertension and
three mothers had gestational diabetes. In these patients who were all followed up
in external centers, the median time of making a diagnosis of NTD by ultrasonography
in the prenatal period was 20 (16–24) weeks. Among 33 patients (47.8%) who were diagnosed
prenatally, 27 (81.8%) were diagnosed as having meningomyelocele and six patients
(18.2%) were diagnosed as having encephalocele. Thirty-six patients (52.2%) could
be diagnosed in the postnatal period.
When familial history of similar disease was investigated, it was found that eight
families (11.6%) had a history of NTD. Consanguineous marriage was found in 11 of
the cases (15.9%); eight of these were second-degree consanguinity, while one was
third-degree consanguinity. Consanguineous marriage was not found in any of the cases
in which familial history of similar disease was positive.
Thirty-nine (56.6%) of the patients had other organ disorders including disorders
involving multiple systems in some cases. Various orthopedic deformities (pes equinovarus,
scoliosis) were found in 17 patients, various cardiac disorders (atrial septal defect,
ventricular septal defect, patent ductus arteriosus, situs inversus totalis, double-outlet
right ventricle, and arcus aorta hypoplasia) were found in 19 patients, urinary system
disorders (hydronephrosis, renal agenesis, hypospadias, ectopic kidney) were found
in seven patients, and cataract was found in one patient.
As a result of physical examination and imaging studies (cranial ultrasonography and
cranial and/or spinal MRI), 49 (71%) of the patients were diagnosed as having meningomyelocele,
11 (16%) were diagnosed as having encephalocele, and 9 (13%) were diagnosed as having
meningocele. Arnold–Chiari type 2 malformation was found in 45 (65.2%) of these patients
and findings related to corpus callosum dysgenesis were found in nine.
Sac excision was performed in 16 of the patients, ventriculoperitoneal (VP) shunt
operation in association with sac excision was performed in 49 patients, and operation
could not be performed in three patients because of exitus or accompanying comorbidities
(one patient had giant encephalocele, one patient had trisomy 18 [this patient who
had multiple organ anomaly could not be intubated because of micrognathia and tracheotomy
was performed], one patient had diaphragm hernia). Antibiotic treatment was initiated
immediately in eight of the patients because cerebrospinal fluid leakage in the sac
was observed after delivery; clinical sepsis developed in the postoperative period
in two of these patients, but VP shunt infection did not develop, and they were discharged
after treatment with appropriate antibiotics. Five of the patients who were operated
died. The reasons for mortality included sepsis following intrauterine gastrointestinal
tract (GIS) perforation secondary to malrotation (one patient) and multiple congenital
anomaly (four patients).
The median time of hospitalization was 22 days (18.5–37.5) excluding the patients
who died.
Discussion
The incidence of NTDs is specified by genetic and environmental factors and may vary
depending on factors including the country's developmental status, race, baby's gender,
and family's socioeconomic and education status.[[9]],[[10]]
The incidence of NTDs has been reported to be 0.89–0.93 in 1000 live births in the
European countries,[[11]] 0.53 in the USA,[[12]] 0.2–9.6 in Latin America,[[13]] and 0.62–13.8 in the Arab countries.[[14]] In our country, the incidence of NTD has been reported to be 5.6[[15]] and 22.6[[16]] in 1000 live births in various studies. Inadequate follow-up of pregnant women,
high rates of consanguineous marriage, and lack of preference for prenatal termination
because of religious beliefs may be the reasons for a higher incidence of NTD in our
country compared to the European countries.
A history of consanguineous marriage was found in 11 of the cases, but they did not
have a familial history of spina bifida. However, a history of spina bifida was found
in the relatives of the parents.
Early prenatal diagnosis in NTDs (especially before the 24–26th week) plays an important
role in terms of therapeutic termination of pregnancy, when necessary.[[17]] The time of prenatal diagnosis was the 24th gestational week and earlier in 29
patients (42%). In our country, the legal borderline for medical termination is the
24th gestational week. The file records revealed that medical termination was offered
to the parents for the cases diagnosed prenatally before the 24th gestational week,
but the families did not accept this. This contributes to the higher incidence of
NTD in our hospital and country compared to developed countries.
Arnold–Chiari type 2 malformation accompanies meningomyelocele at a high rate.[[6]] In our study, Arnold–Chiari type 2 malformation was found with a rate of 65% (45
patients). Similarly, this rate was found to be 71.4% in the study conducted by Çelik
et al.[[16]] Hydrocephaly requiring surgical intervention was found in 71% of the cases which
was an expectedly high rate.
NTDs may also affect the organs outside the nervous system depending on the time they
form in the fetal period.[[18]] We found anomaly in at least one of the organs including heart, eye, kidney, and
skeletal system with a rate of 58%. It has been reported that accompanying anomalies
develop as a result of mechanical action of the disorder in the neural tube and surrounding
tissues and these increase the mortality risk to a significant extent.[[7]]
Folic acid is a substance which is essential for synthesis of intracellular nucleotides
used in DNA synthesis and for the methylation reactions taking place in the cell.
Since the neural tube draft is formed in the early stages of pregnancy, sufficient
folic acid should be available in the environment in the periconceptional period.
It has been shown that folic acid deficiency causes NTDs and use of periconceptional
folic acid decreases NTD recurrence by 50%–70%. Considering that 75% of the mothers
of our patients had never used folic acid, families should be explained that they
should use folic acid in the periconceptional period to decrease NTD recurrence in
subsequent pregnancies. It has been reported that low Vitamin B12 levels during pregnancy
independently increase the risk for NTD.[[19]] Only two of the mothers of our patients had used Vitamin B12. Similarly, mothers
who have not used Vitamin B12 during pregnancy should be informed that they should
use Vitamin B12 in association with periconceptional folic acid in subsequent pregnancies.
Conclusion
It is possible to make the diagnosis in babies with NTDs by ultrasonography from the
early stages of pregnancy. Prenatal diagnosis is delayed in an important portion of
the cases. In cases where the diagnosis is made in time, it is observed that families
decide to continue pregnancy because of sociocultural factors. In NTDs, morbidity
or disorders in other organ systems accompany beside CNS disorders. The patients need
long-term follow-up and collaboration of different clinical branches including pediatrics,
neurosurgery, physical therapy and rehabilitation, and pediatric surgery and the follow-up
process may also be backbreaking for families. Raising awareness of the families of
babies who are diagnosed in the early prenatal period about the prognosis in addition
to studies directed to periconceptional use of folic acid and Vitamin B12 may contribute
to a reduction in sociocultural pressure.
