The importance of neurosurgical intervention and surgical timing for management of pediatric patients with myelomeningoceles in Bangladesh

Abstract

Objective:

Reports on the management and survival of children with myelomeningocele defects in Bangladesh are limited. This study describes the characteristics and outcomes of these children, focusing on the timing of surgical repair and factors affecting survival.

Methods:

We enrolled patients with myelomeningoceles in a case-control study on arsenic exposure and spina bifida in Bangladesh. Cases were subsequently followed at regular intervals to assess survival. Demographic, clinical, and surgical characteristics were reviewed. Univariate tests identified factors affecting survival.

Results:

Between 2016–2022, we enrolled 272 patients with myelomeningocele. Postnatal surgical repair was performed in 63% of cases. However, surgery within 5 days after birth was infrequent (<10%) due to delayed presentation, and there was a high rate (29%) of preoperative deaths. Surgical repair significantly improved patient survival (p<0.0001). Older age at time of surgery was also associated with improved survival rates, which most likely represents that those who survived to older ages prior to surgery accommodated better with their lesions. Patients who presented with ruptured lesions had lower survival rates.

Conclusions:

Timely neurosurgical repair of myelomeningoceles in Bangladesh is hindered by late patient presentation, resulting in a high preoperative patient death rate. Neurosurgical intervention remains a significant predictor of survival. Increased access to neurosurgical care and education of families and non-neurosurgical providers on the need for timely surgical intervention are important for improving the survival of infants with myelomeningoceles.

Objective

Globally, neural tube defects (NTDs) are a leading cause of child morbidity and mortality, affecting as many as 300,000 pregnancies annually.^1–4 Characterized by the failed or abnormal closure of the neural plate during early embryogenesis, NTDs result in congenital malformations including anencephaly and, most commonly, myelomeningocele.^5,6 A growing body of evidence has linked the development of NTDs to a combination of environmental, nutritional, and genetic risk factors.^6–10 Specifically, a lack of maternal folic acid supplementation use and micronutrient deficiencies are widely recognized to contribute to an increased chances of developing a myelomeningocele. Other risk factors include maternal obesity, ethnicity, and perinatal exposure to metals and other teratogenic substances.^7,11–24 Many high-income countries have focused on the prevention of NTDs through folic acid fortification programs. However, in low- and middle-income countries (LMICs) mandatory fortification programs are uncommon and prenatal vitamin adherence tends to be poor, making NTDs such as myelomeningocele—and their clinical management—a particular public health concern.^4,25–28

Data on the prevalence of NTDs in Bangladesh are limited, but some studies estimate it may be as high as 32 per 1000 live births.²⁹ This is nearly sixteen times the global rate of NTDs, which is reported to be between 1.9 and 2.4 per 1000 live births.^1,2 Despite the presence of a government sponsored program that makes folic acid supplements freely available,^30,31 several studies cite low rates of prenatal folic acid supplement use and inadequate folate intake in the maternal diet,^30–34 and folic acid fortification of salts and grains has not been mandated in Bangladesh.^25,29 Additionally, Bangladesh is known to have high concentrations of metal contaminants, such as arsenic, in its drinking water.^35,36 These nutrient deficiencies and heavy metal exposures may put mothers at an increased risk of their children developing an NTD such as myelomeningocele.^16,22,37

The usual timing of surgical treatment for children with myelomeningocele is within 48–72 hours from birth, in order to prevent infection and further neurologic compromise.^5,38 Adhering to this timeline can prove challenging for both providers and families in LMICs, where the prevalence of myelomeningoceles is often high but the infrastructure to provide and access early surgery is lacking.^4,39. Comprehensive data detailing the presentation, surgical timing, and outcomes of children with meningomyeloceles in Bangladesh are limited.⁴⁰ Given the country’s high rate of NTDs, it is important to understand Bangladesh’s experience treating children with myelomeningoceles. This study aims to describe the clinical presentation, management, and survival of children diagnosed with myelomeningocele at a high-volume hospital in Bangladesh, focusing on the timing of postnatal neurosurgical repair and factors associated with survival.

Methods

Study Population

We used data that had been collected as part of a case-control study of arsenic exposure and NTDs in Bangladesh from December 2016 to December 2022.²² Cases were infants under one year of age who presented to the National Institute of Neurosciences & Hospital (NINS&H) for evaluation of a suspected NTD. Only patients with a confirmed diagnosis of myelomeningocele by a neurosurgeon were included in this study.

All procedures were performed in compliance with relevant laws and institutional guidelines. This study was approved by the Bangladesh Medical Research Council (BMRC registration number 006 23 08 2016, approved 23 Aug 2016), and the Institutional Review Boards at NINS&H (ERC-NINS number 2016/07/10, approvedl 1 Aug 2016), Dhaka Shishu Hospital (protocol 2059/2021, approved16 Jun 2021), and Boston Children’s Hospital (protocol number IRB-20–0780, approved 22 Aug 2015). Informed parental consent was obtained for all patients.

Study Variables

Trained study staff interviewed patients’ families to collect demographic characteristics, patient and family medical histories, referral patterns to NINS&H, and information about the child’s birth and whether the mother had used vitamins or supplements before or during pregnancy. We performed a physical exam and used a standardized form to abstract information from patient medical records. Clinical data included level of the lesion, the presence of a cerebrospinal fluid (CSF) leak, lesion infection, hydrocephalus, bladder and/or bowel dysfunction, unilateral or bilateral clubfoot, and skin stigmata. Variables of interest from surgical records included age at the time of surgery, location of the surgery (NINS&H or another institution), and whether any hydrocephalus treatment was performed (i.e., endoscopic third ventriculostomy [ETV] or ventriculoperitoneal [VP] shunt placement). If surgery was not performed, the reason was documented.

We telephoned families at three-month intervals and scheduled follow-up appointments every six-months from the time of enrollment. At each contact point, we recorded whether the patient was still alive and whether surgery had been performed. If the patient died, we recorded the date of death provided by the parents and parent-reported cause of death.

Statistical Analysis

We performed statistical analyses with SAS (version 9.4) and R (version 4.2.2). We tested for differences between children who died and those who survived using Wilcoxon rank sum tests, Student’s t-tests, and Fisher’s exact tests. Statistical significance was set at p<0.05. We further investigated predictors of survival using the Kaplan-Meier method and Cox regression models.

Results

Patient and Parental Demographics

We included 272 infants with myelomeningocele in our study. At presentation, patients were a median of 30.5 days old (IQR: 9, 110) (Table 1). Most families were referred to NINS&H from either division- or district-level care centers (46% and 21%, respectively), although many (29%) patients were referred by family or friends.

Table 1.

Case and parental demographics of children with myelomeningocele (N=272).

Patient Characteristics	Value* (IQR†)	Percentage**
Sex
Male	138	51%
Female	134	49%
Age at presentation
Patient (d)	30.5 (IQR: 9, 110)	-
Mother (yrs)	25 (IQR: 21, 27)	-
Father (yrs)	32 (IQR: 28, 37)	-
Gestational Age, median wks	37 (IQR: 36, 39)	-
Term (37–40 wks)	188	69%
Premature (<37 wks)
Late preterm (34–37 wks)	69	25%
Moderate preterm (32–34 wks)	12	4%
Very preterm (26–32 wks)	3	1%
Any Perinatal Folic Acid Supplementation, total (n)	45	17%
Underwent Prenatal Ultrasound	247/272	91%
Parents reported abnormal ultrasound	19/247	8%
Mode of Delivery
Vaginal	100	37%
Cesarean	157	58%
Vaginal forceps assisted	15	6%
Place of birth
Home	80	29%
Clinic	96	35%
Hospital	96	35%
Division of Residence
Dhaka	139	51%
Chittagong	44	16%
Barisal	22	8%
Khulna	23	8%
Rajshahi	13	5%
Rangpur	4	2%
Sylhet	2	1%
Mymensingh	25	9%
Referral Patterns to NINS&H
Divisional-level hospital or clinic	126	46%
District-level hospital or clinic	58	21%
Upazila (Thana) level hospital or clinic	9	3%
Family or friend	79	29%

^*Frequency variables are reported out of N=272 unless values are missing/not reported or representing a subset of the data; in those cases, the denominator of known values is specified.

^†Indicates continuous variable and interquartile range is specified.

^**Sum of individual percentages may not total 100 due to rounding. Abbreviations: d=days; IQR=interquartile range; NTD= neural tube defect; wks=weeks; yrs=years.

Most infants in our study were delivered at term (69%) or during the late preterm period (25%). Nearly 60% of deliveries were performed by Cesarean section, and 29% of infants were born at home. Antenatal use of folic acid supplements was rare (17%), and despite a high rate (92%) of mothers reporting having at least one ultrasound during pregnancy, parental reports of prenatal ultrasound diagnoses of myelomeningocele defects were uncommon (7%).

Clinical Presentation

Approximately 96% of infants were found to have defects at or below the lumbar level (Table 2). There was also a high a rate of ruptured lesions (captured in our database as preoperative CSF leaks) (54%), lesion infections (37%) and clinical diagnosis of hydrocephalus (52%) at the time of presentation. Just under a third (28%) of patients were found to have a clubfoot deformity. Patients frequently presented with a history of urinary (64%) or bowel (47%) dysfunction. Unfortunately, our ability to further evaluate urologic issues was limited, as patients and their families received urologic care at outside institutions.

Table 2.

Clinical presentation of children with myelomeningoceles (N=272).

Patient Characteristics	Myelomeningocele (N=272)
	Value* (%** or IQR†)
Spinal level of lesion
Cervical	1 (1%)
Thoracic	9 (3%)
Lumbar	128 (47%)
Sacral	19 (7%)
Lumbo-Sacral	115 (42%)
Clinical presentation
Ruptured lesion	148 (54%)
Infected lesion	100 (37%)
Hydrocephalus
Diagnosed at presentation	141 (52%)
Delayed onset	33/131 (25%)
Autonomic Involvement
Urinary issues	175 (64%)
Bowel issues	128 (47%)
Club foot	75 (28%)
Unilateral	26/75 (35%)
Bilateral	48/75 (64%)
Unknown	1/75 (1%)
Skin stigmata	23/230 (10%)
Seizure history	22/271 (8%)

^*Frequency variables are reported out of N=272, unless values are missing/not reported or representing a subset of the data; in those cases, the denominator of known values is specified.

^**Sum of individual percentages may not total 100 due to rounding.

^†Indicates continuous variable and interquartile range is specified. Abbreviations: CSF = cerebrospinal fluid; IQR=interquartile range.

Hydrocephalus

More than half (52%) of the infants in our series had concurrent diagnoses of hydrocephalus, and many were diagnosed shortly after birth in the setting of enlarging head circumference, bulging fontanelle, and ventriculomegaly (Table 2). Most of these patients (75%) went on to receive permanent CSF diversion; for those who did not receive CSF diversion, their symptoms had arrested prior to definitive treatment or families refused surgery. VP shunt placement was the primary mode of CSF diversion (65%), and just over a third of patients (35%) received endoscopic management.

Myelomeningocele Repair

A total of 171 of the 272 patients (63%) in our series underwent surgical repair of their myelomeningocele defect (Table 3). Most of these infants (77%) received surgery at NINS&H. Less than 10% of patients received surgery within five days after birth—and only 3% of patients received surgery within 72-hours after birth. The median age at the time of surgery in our series was 3.6 months (IQR: 0.8–5.7 months) (Table 3).

Table 3.

The surgical management and survival outcomes for patients with myelomeningoceles (N=272).

Patient Characteristics	Myelomeningocele (N=272)
	Value* (%** or IQR†)
Age at myelomeningocele closure, overall (d)	3.6 (0.75, 5.7)
0–5 d	11/171 (6%)
6–15 d	16/171 (9%)
16–30 d	19/171 (11%)
1–3 mo	25/171 (15%)
>3–6 mo	61/171 (36%)
>6–9 mo	15/171 (9%)
>9–12 mo	16/171 (9%)
>1 year	3/171 (2%)
Unknown	5/171 (3%)
Treatment
Surgical repair of myelomeningocele	171/272 (63%)
Surgery at NINS&H	132/171 (77%)
Surgery at OSH	39/171 (23%)
CSF diversion needed	130/174 (75%)
EVD	-
ETV	37/130 (29%)
ETV+CPC	8/130 (6%)
VPS	85/130 (65%)
Reason myelomeningocele closure was not performed
Death prior to DOS	78/101 (77%)
The family did not agree	11/101 (11%)
Doctors did not recommend/contraindicated	7/101 (7%)
Family is waiting for operation	5/101 (5%)
Outcome at last follow-up
Died	124/272 (46%)
Alive	142/272 (52%)
Lost to follow-up	6/272 (2%)
Median age at time of death (d)	3.8 (IQR: 1.3, 7.3)
30-day mortality	17/272 (6%)
1-yr mortality	108/272 (40%)
5-yr mortality	124/272 (46%)
Median time from surgery to death (d)	4.4 (IQR: 2.5, 9)
30-day operative mortality	6/171 (4%)

^*Frequency variables are reported out of N=272 unless values are missing/not reported or representing a subset of the data; in those cases, the denominator of known values is specified.

^**Sum of individual percentages may not total 100 due to rounding.

^†Indicates continuous variable and interquartile range is specified. Abbreviations: CPC= choroid plexus cauterization; d=day(s); DOS = date of surgery; ETV= endoscopic third ventriculostomy; IQR=interquartile range; mo=month(s); OSH = outside hospital. For a qualitative report of the causes of mortality, please reference the results section.

Among the 101 patients who did not receive surgery for their myelomeningocele, the median age at presentation was 17 days, 67 (66%) were ruptured, and 55 (54%) had hydrocephalus at presentation (data not shown). The leading reason for why surgery was not performed was patient death before the planned surgery date (77%). Less commonly, parents refused surgery or the neurosurgical team did not recommend surgery. Notably, the patients who died prior to surgical intervention account for over half (63%) of all patients who died during the entire duration of our study.

Survival

The median time of follow-up was 12 months, and 6 (2%) patients did not have any follow-up recorded. At the time of the last follow-up, 124 (46%) patients had died. The median age at the time of death was 3.8 months (IQR: 1.3–7.3 months), and most patient deaths occurred within the first year of life (Table 3). Patients had a 59% chance of survival during the first 12-months of life (Table 4, Figure 1A). Postoperative complications relating to the patient’s myelomeningocele repair or a shunt malfunction were overall infrequent and rarely associated with patient death (1.6% and 3%, respectively). Patient death during the 30-day postoperative period following myelomeningocele repair was 4%; therefore, most patients died at home or upon return to the hospital in the setting of other worsening health conditions. According to parental reports, the most common cause of death among the infants in our series included respiratory distress (47%), followed by dehydration (12%), unspecified infections and fevers (12%), pneumonia (10%), cardiac arrest of unspecified etiology (8.0%), postoperative (including myelomeningocele repair and VP shunt-related) complications (5%), unspecified respiratory disorders (3%), and others (2%).

Table 4.

Kaplan Meier Estimates of Survival by surgical status.

Characteristic	1mo Survival (95% CI)	12mo Survival (95% CI)
Diagnosis
Myelomeningocele	94% (91%, 97%)	59% (53%, 65%)
Surgical status
No	83% (76%, 91%)	18% (12%, 27%)
Yes	100% (100%, 100%)	84% (78%, 90%)

Abbreviations: CI = confidence interval; mo=months.

Figure 1.

Kaplan Meier curve demonstrating overall survival estimates for (A) all (N=272) patients with myelomeningocele in our series up to 48 months of age and (B) survival estimates for patients with surgically repaired myelomeningoceles compared to those who did not receive surgery (p<0.0001).

When considering preoperative factors, rupture of the myelomengingocele at the time of presentation (captured in our data as CSF leak) significantly increased the risk of patient mortality (HR 1.9, 95% CI: 1.3–2.7; HR 2.3, 95% CI: 1.6–3.3) (both p<0.05, Tables 5–6). Despite the high rate of hydrocephalus (52%) among patients in our series, hydrocephalus at the time of presentation or the need for CSF diversion did not predict worse overall survival. While urologic disorders and renal issues are recognized contributors to adverse outcomes in patients with myelomeningoceles,⁴¹ the presence of urinary or bowel dysfunction was not associated with worse survival in our series. Delivery modality (Cesarean section versus vaginal delivery) and delivery location (at home or in a clinic/hospital) were not associated with survival outcomes. Patients who presented at an older age (median age of 2 versus 0.6 months) were significantly more likely to survive than those who presented soon after birth (p<0.0001 and p=0.016, Tables 5–6).

Table 5.

Univariate analysis for factors associated with mortality or survival during the study period.

Patient Characteristics	Myelomeningocele
	Alive (n=142)	Dead (n=124)	P-Value
Sex
Male	70 (49%)	65 (52%)	0.63
Female	72 (51%)	59 (48%)
Gestational age (wk), IQR	37 (36, 39)	37 (36, 39)	0.47
Age presentation (mo), IQR	2 (IQR: 0.4, 5)	0.6 (IQR: 0.2, 2.0)	<.0001 *
Age at surgery, IQR	3.8 (IQR: 2, 5.9)	1.8 (IQR: 0.5, 4)	0.004 *
0–5 d	7/124 (6%)	4/36 (11%)	0.02 *
6–15 d	12/124 (10%)	4/36 (11%)
16–30 d	9/124 (7)	7/36 (19%)
1–3 mo	15/124 (12%)	9/36 (25%)
>3–6 mo	52/124 (42%)	7/36 (19%)
>6–9 mo	11/124 (9%)	4/36 (11%)
>9–12 mo	15/124 (12%)	1/36 (3%)
>1 year	3/124 (2%)	-
Mode of Delivery
Vaginal	47 (33%)	50 (40%)	0.37
Cesarean	88 (62%)	66 (53%)
Vaginal Forceps	7 (5%)	8 (7%)
Place of birth
Home	39 (27%)	39 (31%)	0.78
Clinic	51 (36%)	42 (34%)
Hospital	52 (37%)	43 (35%)
Surgical repair of myelomeningocele
Yes	129 (91%)	36 (29%)	<0.0001 *
No	13 (9%)	88 (71%)
Hydrocephalus
Yes	96 (68%)	74 (60%)	0.20
No	46 (32%)	50 (40%)
Ruptured lesion
Yes	66 (46%)	79 (64%)	0.007 *
No	76 (54%)	45 (36%)
Infected lesion
Yes	36 (25%)	61 (49%)	<0.0001 *
No	106 (75%)	63 (51%)
Urinary involvement
Yes	95 (67%)	75 (60%)	0.31
No	47 (33%)	49 (40%)
Bowel involvement
Yes	65 (46%)	59 (48%)	0.81
No	77 (54%)	65 (52%)

Categorical data are presented as n (%), and continuous variables as median (Q1, Q3). The denominators of fractions represent the number of patients with available data if values are different from the reported group size for each column. Sum of individual percentages may not total 100 due to rounding. Six patients from the original series did not participate in any follow-up calls. Abbreviations: CSF = cerebrospinal fluid leak; IQR=interquartile range; mo=month(s); OSH = other hospital.

^*Statistical significance (p<0.05).

Table 6.

Univariate Cox regression analysis of survival in children with myelomeningocele defects.

Patient Characteristics	Univariate Estimates
	HR (95% CI)	P-Value
Sex (ref: female)	0.90 (0.63–1.28)	0.56
Gestational age	0.98 (0.91–1.06)	0.66
Term/Post-Term (ref: preterm)	0.79 (0.55–1.14)	0.21
Age at clinical presentation (mo)	0.80 (0.73–8.73)	<0.0001 *
Age at surgery (d)	0.99 (0.988–0.997)	0.00073 *
0–5 d	Ref
6–15 d	0.71 (0.18–2.86)	0.63
16–30 d	1.55 (0.42–5.0)	0.55
1–3 mo	0.82 (.25–2.69)	0.75
>3–6 mo	0.23 (0.067–0.81)	0.022 *
>6–9 mo	0.44 (0.11–1.76)	0.24
>9 mo	0.09 (0.012–0.95)	0.031 *
Mode of Delivery
Cesarean	Ref
Vaginal	1.4 (0.94–2.0)	0.1
Vaginal Forceps assisted	1.3 (0.61–2.7)	0.52
Place of birth
Hospital	Ref
Clinic	1.0 (0.68–1.6)	0.86
Home	1.2 (0.82–0.79)	0.37
Surgical management (ref: yes)	10.2 (6.8–15.4)	<0.0001 *
Hydrocephalus(ref: no hydrocephalus)	0.72 (0.50–1.03)	0.07
Clinical Presentation at Enrollment
CSF leak (ref: no)	1.9 (1.3–2.7)	0.00065 *
Infected lesion (ref: no)	2.3 (1.6–3.3)	<0.0001 *
Autonomic involvement, Urinary (ref: no)	0.81 (0.56–1.2)	0.239
Autonomic involvement, Bowel (ref: no)	1.0 (0.74–1.5)	0.80

^*Statistical significance (p<0.05). Abbreviations: CSF= Cerebrospinal Fluid; CI = confidence interval; d=day(s); IQR=interquartile range; mo=month(s); HR= hazard ratio; ref=reference.

Patients who underwent surgical repair of their myelomeningocele were significantly more likely to be alive at the time of the last follow-up visit (p<0.0001) (Table 5–6, Figure 1B). Those who received surgery for their lesion had an 84% chance of 1-year survival (Table 4), which is markedly higher than the 18% chance of 1-year survival in patients who did not receive surgery (p<0.0001). Patients who received surgery at an older age, often older than 3-months, were also significantly more likely to survive than those who received surgery earlier (p<0.05, Tables 5–6); this difference likely reflects that patients who survived to have surgery at older ages had lesions that were better accommodated.

Discussion

We describe the clinical characteristics, time to surgery, and survival for 272 patients with myelomeningoceles in Bangladesh. To our knowledge, this is one of the largest reports to comment on the neurosurgical management and overall survival of patients with myelomeningoceles in Bangladesh.

Clinical and Prenatal Characteristics

Consistent with other institutional series, myelomeningocele affecting the lumbar and lumbosacral regions of the spine accounted for most (94%) cases.^41–47 We also identified comparable rates of hydrocephalus (52%)^43,48–51 and clubfoot deformities (25.8%).^47,52,53 Regarding prenatal characteristics, we observed a low rate (17.6%) of any antenatal folic acid intake among the mothers in our study, which aligns with the findings of other studies in Bangladesh.^31,34

Because NINS&H does not offer obstetrical services, all patients were delivered at an outside institution or at home, with families subsequently referred to our center for neurosurgical care. Although 91% of parents reported prenatal care that included an ultrasound, only 8% of these parents reported receiving an abnormal result. As a result, being diagnosed at birth with their myelomeningocele defect was common. We were not able to review ultrasound imaging or reports, and instead collected this information through parental reports, thereby limiting our ability to assess the quality of prenatal ultrasounds. However, a recent study found that the majority of ultrasound providers in LMICs do not have the minimum training as set by the World Health Organization (WHO).⁵⁴ Detection rates of congenital anomalies by ultrasound in LMICs are highly variable, and termination of pregnancy remains a sensitive topic in many communities.^46,54–60 In our setting, it is likely that all of these factors led to barriers in prenatal planning.

Surgical Timing

In our series, delayed patient presentation was common and often contributed to the suboptimal timing of surgery. Among all patients, the median age at presentation to our institution was 30.5 days, and for those who underwent surgery, the median age at surgery was 3.6 months. Despite wide agreement in our neurosurgical community that surgery for myelomeningoceles is recommended within 72 hours post-birth,⁵ only five of our 272 patients (1.8%) received surgery during this period. Unfortunately, similar patterns of delayed repair are frequently reported in other LMICs, highlighting the ongoing challenge of providing timely surgical intervention in these settings.^43,50,61,62

Survival

Our study is among the first to document both overall survival and factors associated with mortality in pediatric patients with myelomeningoceles in Bangladesh. Just under half (40%) of the patients in our series died during their first year of life, and most of these patient deaths occurred in individuals who did not undergo surgery. Of children who died prior to any surgical intervention, the majority (64%) had ruptured lesions at the time of presentation. The mortality rates observed in this study are consistent with the 19–37% mortality rates documented in other LMIC series.^47,51,63,64

Neurosurgical intervention improved the overall survival of patients in our series. Moreover, we found low rates of surgical complications and operative mortality in our study (1.6% and 4%, respectively). In our setting, infants over age 2.5 months are considered for ETV, although the choice of procedure often depends on technical factors such as availability of flexible endoscope. While surgery itself was safe, it is important to note that some (16%) of the patients who received surgery died in the year following surgery, underscoring the need for ongoing, multidisciplinary care, such as anticipatory teaching about respiratory complications that might indicate worsening hydrocephalus.

Timely surgery remains the gold standard for improving the prognosis of patients with myelomeningoceles.⁶⁷ While we observed a significant correlation between the age at the time of closure and survival status, the relationship was opposite to our expectation. We believe the better outcomes among older patients most likely reflects that those who survived to present at older ages were able to better accommodate their lesions and/or experienced myelomeningocele sac epithelization,⁵⁰ while patients with more severe and complex presentations tended to die prior to presentation.

In Bangladesh, there is approximately one neurosurgeon for every million people and sixteen medical centers that provide neurosurgical services.⁶⁵ Recent reviews discuss strategies to increase the neurosurgical and healthcare workforce to address the clinical needs of children with myelomeningoceles in LMICs, and recommend more active neurosurgical involvement in education and advocacy for preventive strategies (for example, folic acid fortification).⁶⁶

Limitations

Despite NINS&H being a high-volume neurosurgical care center, our study remains limited by its single-institution design. As a result, our findings may not be generalizable to the broader Bangladeshi population, particularly those living in rural areas who may not be able to seek care in Dhaka. We were limited in our ability to comment on urologic and orthopedic data due to the because children received this care at facilities other than NINS&H. Our study did not have adequate data on the presence of concurrent intracranial and intraspinal abnormalities, such as Chiari II malformation, tethered cord, and syringomyelia, as only a limited number of patients had brain and/or spinal MRIs available for review. Additionally, the collection of longer-term hydrocephalus outcomes was beyond the scope of our study; therefore, information regarding the rate of redo-ETV or shunt revisions was not available. We also have limited information about lifestyle other than survival.

Recommendations

We propose the following two areas of improvement to support the prevention of NTDs and strengthen the overall management of children with myelomeningoceles in Bangladesh.

1. Folic acid fortification. Myelomeningocele is a largely preventable congenital anomaly, especially since the establishment of mandated food fortification programs, which have successfully reduced the prevalence of myelomeningocele and other NTDs in many countries.^1,25,27,29 Previous reports have identified Bangladesh as having high potential for mandatory food fortification,⁶⁷ with estimates that as many as 4,154 NTDs could be averted per year if mandatory folic acid fortification of rice and/or wheat flour were achieved.²⁵ Additionally, double fortification of iodized salt with folic acid may be another promising avenue to pursue.⁶⁸ The WHO recommends that all women, from the movment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement (400 μg folic acid daily), and that women who have had a NTD-affected pregnancy be offered high-dose supplementation (5 mg folic acid daily).⁶⁹ Given the very low rates of prenatal folic acid use in our series, as well as the body of literature documenting poor folate intake in maternal diets in Bangladesh,^31–34 we advocate for the implementation of a mandatory folic acid fortification program to reduce the overall morbidity and prevalence of myelomeningoceles and other NTDs in Bangladesh.

2. Education and referrals. In order to improve timely access to neurosurgical care, it is imperative that non-neurosurgical providers receive education on the significance of expedient referral to a neurosurgical care center when mothers are expecting a child with an NTD.^51,58,60 In Bangladesh, where as many as 30–60% of births continue to occur at home,^70,71 and care referrals are often suggested by family members and friends, as was observed in our series, this education should also encompass the general public, physicians, and other healthcare providers like ultrasonographers, midwives, and community health workers.

Conclusion

Timely neurosurgical repair of myelomeningoceles in Bangladesh is complicated by delayed referral to neurosurgical centers and complex patient presentations. Despite these challenges, neurosurgical repair remains a significant predictor of survival in infants with myelomeningocele and our series reports a low rate of postoperative complications. Our study details the current neurosurgical management of patients with myelomeningoceles in Bangladesh and identifies areas for future improvement. Increasing neurosurgical access, educating the general public, physicians, and other healthcare providers on the need for timely neurosurgical intervention, and implementing comprehensive prevention strategies, like mandatory folic acid fortification and improved prenatal care, are critical.

Abbreviations list:

CI

Confidence Interval

CNS

Central Nervous System

CSF

Cerebrospinal Fluid

ETV

Endoscopic Third Ventriculostomy

HR

Hazard Ratio

IQR

Interquartile Range

LMIC

Low- and Middle-Income Country

MRI

Magnetic Resonance Imaging

NINS&H

National Institute of Neurosciences and Hospital

NTD

Neural Tube Defects