The data of 13,710,479 individuals enrolled in JMDC between January 1, 2005, and October 31, 2021 (Fig. 2) were available.

Flow of patients. *The index month was the first month of NGB diagnosis, OAB diagnosis, or OAB drug prescription. NGB, neurogenic bladder; OAB, overactive bladder

Of those enrolled, 883 children met our inclusion criteria. The spina bifida cohort comprised 347 (39.3%) of these children while the non-spina bifida cohort included the remaining 536 (60.7%) children. The spina bifida cohort included 127 (36.6%) children with open spina bifida and 220 (63.4%) children with occult spina bifida. The non-spina bifida cohort mainly included children with cerebral palsy (74.1%), brain tumor (7.1%), and meningitis (6.5%) (Supplementary Material Table S4).

The overall and cohort-wise baseline and demographic characteristics of these children are presented in Table 1. With 59.8% being male, the cohort showed male predominance. The mean [SD] age of children with NGB was 6.7 [4.7] years; the age of children in spina bifida cohort (5.0 [4.5] years) was significantly lower than that in the non-spina bifida cohort (7.8 [4.5] years; P < 0.01). Furthermore, the age of those with open spina bifida (0.6 [1.4] years) was significantly lower than those with spina bifida occulta (7.5 [3.7] years; P < 0.01). The baseline characteristics showed that the common comorbidities involved the skin (dermatitis, 41.2%; xerosis cutis, 34.1%) and gastrointestinal system (constipation, 38.8%; gastroenteritis and colitis, 35.1%; other unspecified gastroenteritis and infectious colitis, 9.1%). The non-spina bifida cohort had higher comorbidities than the spina bifida cohort (Table 1).

Investigations specifically needed in NGB management were not commonly performed during 12- and 24-month follow-up period (Table 2). Over the subsequent 24 months, the proportions of patients who did not undergo urodynamics (87.4%), cystourethrography during urination (93.2%), and static renal scintigraphy (97.8%) were very high. Over the subsequent 12/24 months, these tests were performed at least three times in a small proportion of patients: urodynamics, 2.0%/5.0%; cystourethrography during urination, 0.7%/1.6%; and static renal scintigraphy, 0.0%/0.1%. Generally, the specific tests were performed more frequently for the children with spina bifida vs. non-spina bifida, and within spina bifida cohort for open spina bifida vs. spina bifida occulta.

Over the subsequent 12/24 months, the proportion of the following tests performed at least once was as follows: renal urinary tract ultrasound and urinalysis, > 35%/> 45%; urine culture, 15.1%/19.0%; and residual urine measurement, 7.0%/9.4%. Generally, the common tests were performed more frequently for spina bifida than non-spina bifida cohorts. Children with open spina bifida were frequently assessed compared to those with spina bifida occulta, except for urine culture and renal urinary tract ultrasound (Table 2).

Continuity of investigations was assessed among those who had undergone a test between 1 and 12 months after the index month and the results are presented in Table 3. Specific tests had been repeated at least once between 13 and 24 months after month 0 in a very small proportion of patients: urodynamics, 4.5%; cystourethrography during urination, 1.9%; and static renal scintigraphy, 0.1%. The specific tests were performed more commonly in children with vs. without spina bifida and in those with open vs. occult spina bifida.

The details of pharmaceutical treatment for NGB administered over 24 months of follow-up are presented in Table 4. OAB medications were used in 21.5% of all patients, especially those with spina bifida occulta (40.9%). The OAB medications were more commonly prescribed to those with (36.0%) vs. without (12.1%) spina bifida (P < 0.01); a similar pattern was evident across all anticholinergic drugs, the number of medicines prescribed, and use of CIC alone or concomitantly with drugs. Anticholinergic medicines were the most widely prescribed OAB medications; among those who used OAB medications, anticholinergics alone were used in most cases (95.3%). Of all the patients, 10.8% underwent CIC of which 50% were prescribed medicines concomitantly. CIC was significantly more common in those with vs. without spina bifida (17.3% vs. 6.5%, P < 0.01) and in those with open vs. occult spina bifida (31.5% vs. 9.1%, P < 0.01).

The surgical follow-up period was 56 months (mean), 47 months (median), 12 months (minimum), and 189 months (maximum) (data not shown). The number of surgeries performed was very small: only 11 of 883 (1.2%) patients underwent surgical treatment; surgeries for bladder augmentation, vesicoureteral reflux prevention, and urinary diversion were performed in one (0.1%), six (0.7%), and four (0.5%) patients, respectively. No surgeries for prevention of urinary incontinence were performed.

The proportion of complications occurring over the follow-up duration of 24 months is shown in Table 5. The common incident complications were lower UTI (23.3%), urinary incontinence (9.7%), and hydronephrosis (7.0%). The complications such as lower UTI, urinary incontinence, hydronephrosis, obstructive uropathy, and vesicoureteral reflux were significantly more common in the children with vs. without spina bifida (P < 0.01). Furthermore, those with open vs. occult spina bifida had significantly higher incidence of most complications (upper UTI, lower UTI, sepsis/septicemia). Contrastingly, those with occult vs. open spina bifida had significantly higher incidence of some complications such as urinary incontinence and frequent urination/frequent urination at night.

The multivariate adjusted odds ratios (ORs) for the risk factors for UTI during the follow-up duration of 24 months are demonstrated in Fig. 3. The adjusted risk was significantly higher for CIC (5.70), hospitalization (5.02), presence of spina bifida (2.86), constipation (2.07), and dermatitis, unspecified (1.59).

Adjusted odds ratios† for development of urinary tract infection in the 24-month follow-up as per our multivariate analysis. CI, confidence interval; CIC, clean intermittent catheterization; OAB, overactive bladder; OR, odds ratio. *P < 0.05, **P < 0.001. †Adjusted for diagnosis of spina bifida (reference category, no), sex (reference category, male), age at the index month (continuous), hospitalization at the baseline, presence of comorbidities at the baseline (dermatitis, unspecified [L309]; constipation [K590]; xerosis cutis [L853]; gastroenteritis and colitis of unspecified origin [A099]; cramp and spasm [R252]; epilepsy, unspecified [G409]; scoliosis, unspecified [M419]; dislocation of hip [S730]; developmental disorder of speech and language, unspecified [F809]; other and unspecified gastroenteritis and colitis of infectious origin [A090]; reference category for each comorbidity, no), use of CIC at the index month (reference category, no), and use of OAB drugs at the index month (reference category, no)

Furthermore, 2.8%/11.8% of children had four or more repeated upper/lower UTI (Fig. 4). Patients within spina bifida cohort were more likely to have multiple events of upper/lower UTI than within non-spina bifida cohort (P = 0.26/P < 0.01). Furthermore, those within the open vs. occult spina bifida cohort were more likely to have multiple events of upper/lower UTI (P = 0.04/P < 0.01).

Number of events of a upper and b lower urinary tract infection. NGB, neurogenic bladder. Data in tables presented as n (%) calculated horizontally. **P < 0.01 between the spina bifida and non-spina bifida cohorts by the chi-square test or Fisher’s exact test. †P < 0.05, ††P < 0.01 between the open spina bifida and spina bifida occulta cohorts by the chi-square test or Fisher’s exact test