Abstract
Background
Risk factors for paediatric inguinal hernia are poorly understood. This longitudinal cohort study assessed whether children with a maternal history of inguinal hernia or connective tissue disorders have a higher risk of developing inguinal hernias before 13 years of age.
Methods
The study included children followed up between birth and 13 years of age in Quebec, Canada, 2006–2019. Newborns whose mothers had inguinal hernias or connective tissue disorders were followed over time to identify future hospital admissions for inguinal hernia. Cox proportional hazards regression adjusted for patient characteristics was used to estimate hazard ratios (HRs) and 95 per cent confidence intervals for the association between maternal hernia or connective tissue disorders and future childhood hernias. Associations in girls and boys were examined separately.
Results
The study included 786 322 children with 6 186 448 person-years of follow-up. There were 6861 children with inguinal hernias, corresponding to an incidence of 11.1 per 10 000 person-years. Children with a maternal history of inguinal hernia had 2.92 (95 per cent c.i. 2.39 to 3.58) times the risk of having inguinal hernias relative to children whose mothers had no such history. Children with a maternal history of connective tissue disorders had 1.30 (1.00 to 1.68) times the risk. Maternal hernias were strongly associated with risk of inguinal hernias in girls (HR 5.34, 3.82 to 7.47), whereas maternal connective tissue disorders were associated with inguinal hernias in boys (HR 1.35, 1.02 to 1.79).
Conclusion
Paediatric inguinal hernias may be associated with maternal inguinal hernias and connective tissue disorders, but the underlying reason for this relationship requires further investigation.
In this cohort study of over 785 000 children, maternal inguinal hernia was associated with risk of paediatric inguinal hernias, especially in girls. Maternal connective tissue disorders were associated with risk of inguinal hernias in boys only.
Introduction
Inguinal hernias occur in up to 4 per cent of children and are among the most common indications for paediatric surgery1,2. Although inguinal hernias are commonly diagnosed in childhood, most are thought to have a congenital origin1,3. Inguinal hernias occur owing to incomplete obliteration of the processus vaginalis during fetal development and are therefore considered to be birth defects1,3. Although there is substantial evidence that congenital birth defects have a familial component4, the evidence is not as clear for paediatric inguinal hernia. Some studies have suggested that children with a family history of hernias may be more likely to develop inguinal hernia5,6, and that women with inguinal hernias may have a greater risk of having children who develop hernias7. The maternal risk factors for paediatric inguinal hernia are, however, unclear.
As part of the pathophysiology of inguinal hernia may involve connective tissue architecture8,9, a relationship with pre-existing maternal connective tissue disorders is plausible. Connective tissue disorders may share indirect pathways with pathologies such as inguinal hernia, where connective tissue integrity is also breached. Connective tissue disorders are common in women of reproductive age10,11, but the possibility of an association with paediatric inguinal hernias has not been considered. This study used a large cohort of more than 780 000 children to investigate whether children whose mothers had inguinal hernias or connective tissue disorders have a greater risk of developing inguinal hernias.
Methods
Study design and data
This longitudinal cohort study included children born in hospitals of Quebec, Canada, between 2006 and 2016. The cohort is representative of the population as more than 98 per cent of births occur in hospital in Quebec12. Data were obtained from the Maintenance and Use of Data for the Study of Hospital Clientele database, which contains discharge abstracts for all clinical diagnoses and procedures during admisson13. The data include hospital admissions for inpatient care including same-day surgery. The data are verified using rigorous algorithms13, and previous studies14–19 have indicated that they have high validity for diagnostic and procedural codes.
Children were linked with their mothers, and health insurance numbers were used to follow the children over time from birth until admission to hospital for inguinal hernia repair or treatment. Follow-up ended on 31 March 2019. Each resident of Quebec has a unique health insurance number that can be used to identify hospitalizations anywhere in the province. Stillbirths and infants without health insurance numbers were not included because they could not be followed over time. A total of 280 children of women with genetic disorders of connective tissue, such as osteogenesis imperfecta, Ehlers–Danlos syndrome, and Marfan syndrome, were excluded to reduce confounding, because these disorders are known causes of hernia8. Femoral hernias were not included, as the pathogenesis may differ from that of inguinal hernias.
As data were anonymous, the institutional review board of the University of Montreal Hospital Centre provided a waiver for informed consent and ethical review.
Inguinal hernia
The primary outcome was hospital admission for inguinal hernia any time between birth and the end of the study. Children could be hospitalized for repair or management of symptomatic inguinal hernias. Because hospital care is funded publicly in Quebec, all inguinal hernia repairs were included in the data set. The ICD-10 code K40 was used to identify inguinal hernia. Unilateral versus bilateral hernias at time of presentation were included as a secondary outcome measure3.
Maternal risk factors
Two main types of exposure were considered: maternal inguinal hernia and maternal connective tissue disorders. All admissions for maternal hernia repair or treatment were identified between 1989 and 2019. The study had up to 31 years of follow-up for women.
Similarly, women with connective tissue disorders, including rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and other rare disorders (scleroderma, ankylosing spondylitis, polyarteritis nodosa and related conditions, other necrotizing vasculopathies, dermatopolymyositis, sclerosis, other) were identified. As these connective tissue disorders are autoimmune diseases, autoimmune disorders that are not classified as connective tissue disorders were included as a negative control (autoimmune inflammatory vasculitis, type 1 diabetes, autoimmune haemolytic anaemia, Graves’ disease, Guillain–Barré syndrome, autoimmune thyroiditis, coeliac disease, multiple sclerosis, myasthenia gravis, Lambert–Eaton myasthenic syndrome, stiff-person syndrome, Addison’s disease, antiphospholipid syndrome, autoimmune haemophilia, dermatitis herpetiformis, Evans’ syndrome, autoimmune hepatitis, pemphigus, pemphigoid bullous, autoimmune polyendocrinopathy, polyglandular autoimmune syndromes, ulcerative colitis, vitiligo, alopecia areata, other autoimmune disease)20. Maternal connective tissue disorders were identified from the prenatal chart, and also from other hospital admissions for these disorders over time.
There were thus three separate exposure measures available for analysis: maternal inguinal hernia, maternal connective tissue disorders, and other maternal autoimmune disorders. ICD-9 and -10 codes were used to identify the disorders (Table S1). Women with neither of these disorders were used as the reference group. Exposures were not mutually exclusive; however, only 38 children had a mother with both inguinal hernias and connective tissue disorders.
Co-variables
Several potential confounders were considered, including: maternal age at delivery (less than 25, 25–34, 35 or more years), maternal co-morbidity (pre-eclampsia, gestational diabetes, epilepsy, mood disorder, anaemia, obesity, or substance, alcohol or tobacco use disorder; yes, no)21, parity (0, 1, 2 or more previous deliveries), infant sex (male, female), multiple birth (yes, no), preterm birth (yes, no), socioeconomic deprivation (yes, no, unknown), and time interval of birth (2006–2009, 2010–2012, 2013–2016). Socioeconomic deprivation represents the most disadvantaged fifth of the population based on census data for average personal income, neighbourhood employment rate, and proportion without a high school diploma22.
Statistical analysis
The incidence of paediatric inguinal hernia per 10 000 person-years of follow-up was calculated. To evaluate the association between maternal risk factors and inguinal hernia, Cox proportional hazards regression analysis adjusted for patient characteristics was used. Hazard ratios (HRs) with 95 per cent confidence intervals were estimated. To account for siblings with the same mother, robust error estimators were used. The number of days from birth to the first hospital admission for inguinal hernia, death, or the end of the study was used as the time scale. Children who never had an inguinal hernia before the end of the study were censored, and the Fine and Gray method was used to account for death as a competing event23. Because sex is strongly associated with the risk of paediatric inguinal hernia3, the association with maternal risk factors was examined in sex-stratified models. Time interaction terms were also used to assess the proportionality of hazards and estimate age-specific associations24.
In sensitivity analyses, analyses were rerun excluding preterm infants. Paediatric inguinal hernias are more frequent following preterm births3,25. Analyses were also repeated after partitioning children whose mothers had both inguinal hernias and connective tissue disorders. Data analyses were conducted in SAS® version 9.4 (SAS Institute, Cary, NC, USA).
Results
There were 786 322 children and 6 186 448 person-years of follow-up in this study (Table 1). Children with a maternal history of inguinal hernia tended to have younger mothers. Compared with those with no history of maternal disorder, children with a maternal history of connective tissue disorders were more likely to be preterm and have mothers with co-morbidity. The mean age of boys and girls with inguinal hernia was 7.9 years at the time of hospitalization.
Table 1.
Characteristics of children whose mothers had inguinal hernias, connective tissue disorders, and other autoimmune disorders
| No. of children |
||||
|---|---|---|---|---|
| Maternal inguinal hernia | Maternal connective tissue disorder * | Other maternal autoimmune disorder † | No maternal disorder | |
| Maternal age (years) | ||||
| < 25 | 1090 (24.6; 23.3, 25.9) | 715 (14.8; 13.8, 15.8) | 1559 (13.0; 12.4, 13.6) | 122 235 (16.0; 15.9, 16.0) |
| 25–34 | 2782 (62.7; 61.3, 64.1) | 3194 (65.9; 64.6, 67.2) | 7967 (66.2; 65.3, 67.0) | 512 447 (66.9; 66.8, 67.0) |
| ≥ 35 | 565 (12.7; 11.8, 13.7) | 936 (19.3; 18.2, 20.5) | 2509 (20.8; 20.1, 21.6) | 131 252 (17.1; 17.1, 17.2) |
| Maternal co-morbidity ‡ | ||||
| Yes | 594 (13.4; 12.4, 14.4) | 1135 (23.4; 22.3, 24.6) | 4407 (36.6; 35.8, 37.5) | 99 964 (13.1; 13.0, 13.1) |
| No | 3843 (86.6; 85.6, 87.6) | 3710 (76.6; 75.4, 77.7) | 7628 (63.4; 62.5, 64.2) | 665 970 (86.9; 86.9, 87.0) |
| Parity | ||||
| 0 | 2094 (47.2; 45.7, 48.7) | 2223 (45.9; 44.5, 47.3) | 5470 (45.5; 44.6, 46.3) | 375 221 (49.0; 48.9, 49.1) |
| 1 | 1545 (34.8; 33.4, 36.2) | 1698 (35.0; 33.7, 36.4) | 4363 (36.3; 35.4, 37.1) | 268 043 (35.0; 34.9, 35.1) |
| ≥ 2 | 798 (18.0; 16.9, 19.1) | 924 (19.1; 18.0, 20.2) | 2202 (18.3; 17.6, 19.0) | 122 670 (16.0; 15.9, 16.1) |
| Infant sex | ||||
| M | 2234 (50.3; 48.9, 51.8) | 2464 (50.9; 49.4, 52.3) | 6185 (51.4; 50.5, 52.3) | 392 800 (51.3; 51.2, 51.4) |
| F | 2203 (49.7; 48.2, 51.1) | 2381 (49.1; 47.7, 50.6) | 5850 (48.6; 47.7, 49.5) | 373 134 (48.7; 48.6, 48.8) |
| Twin or triplet birth | ||||
| Yes | 65 (1.5; 1.2, 1.9) | 84 (1.7; 1.4, 2.1) | 169 (1.4; 1.2, 1.6) | 10 082 (1.3; 1.3, 1.3) |
| No | 4372 (98.5; 98.1, 98.8) | 4761 (98.3; 97.9, 98.6) | 11 866 (98.6; 98.4, 98.8) | 755 852 (98.7; 98.7, 98.7) |
| Preterm birth | ||||
| Yes | 299 (6.7; 6.0, 7.5) | 504 (10.4; 9.6, 11.3) | 1450 (12.0; 11.5, 12.6) | 47 782 (6.2; 6.2, 6.3) |
| No | 4138 (93.3; 92.5, 94.0) | 4341 (89.6; 88.7, 90.4) | 10 585 (88.0; 87.4, 88.5) | 718 152 (93.8; 93.7, 93.8) |
| Socioeconomic deprivation | ||||
| Yes | 865 (19.5; 18.4, 20.7) | 1011 (20.9; 19.7, 22.0) | 2339 (19.4; 18.7, 20.2) | 150 193 (19.6; 19.5, 19.7) |
| No | 3368 (75.9; 74.6, 77.1) | 3654 (75.4; 74.2, 76.6) | 9187 (76.3; 75.6, 77.1) | 583 548 (76.2; 76.1, 76.3) |
| Time interval | ||||
| 2006–2009 | 1672 (37.7; 36.3, 39.1) | 1926 (39.8; 38.4, 41.1) | 4628 (38.5; 37.6, 39.3) | 294 569 (38.5; 38.3, 38.6) |
| 2010–2012 | 1365 (30.8; 29.4, 32.1) | 1480 (30.5; 29.3, 31.9) | 3798 (31.6; 30.7, 32.4) | 237 453 (31.0; 30.9, 31.1) |
| 2013–2016 | 1400 (31.6; 30.2, 32.9) | 1439 (29.7; 28.4, 31.0) | 3609 (30.0; 29.2, 30.8) | 233 912 (30.5; 30.4, 30.6) |
| Total | 4437 (100) | 4845 (100) | 12 035 (100) | 765 934 (100) |
Values in parentheses are percentages with 95 per cent confidence intervals.
*Rheumatoid arthritis, systemic lupus erythematosus, psoriasis, other connective tissue disorder.
†Autoimmune inflammatory vasculitis, type 1 diabetes, autoimmune haemolytic anaemia, Graves’ disease, Guillain–Barré syndrome, autoimmune thyroiditis, coeliac disease, multiple sclerosis, myasthenia gravis, Lambert–Eaton myasthenic syndrome, stiff-person syndrome, Addison’s disease, antiphospholipid syndrome, autoimmune haemophilia, dermatitis herpetiformis, Evans’ syndrome, autoimmune hepatitis, pemphigus, pemphigoid bullous, autoimmune polyendocrinopathy, polyglandular autoimmune syndromes, ulcerative colitis, vitiligo, alopecia areata, other autoimmune disease.
‡Pre-eclampsia, gestational diabetes, epilepsy, mood disorder, anaemia, obesity, and substance, alcohol or tobacco use disorder.
Overall, 6861 children developed inguinal hernias during the study, giving a rate of 11.1 per 10 000 person-years. The incidence was greater for children whose mothers had inguinal hernias (31.2 per 10 000 person-years) and connective tissue disorders (15.6 per 10 000 person-years) than for those whose mothers had no disorder (10.9 per 10 000 person-years) (Table 2). Children whose mothers had inguinal hernias had 2.92 (95 per cent c.i. 2.39 to 3.58) times the risk of developing inguinal hernias compared with those whose mothers had no disorders. Connective tissue disorders were associated with 1.30 (1.00 to 1.68) times the risk of paediatric inguinal hernia. The number of children exposed to specific types of connective tissue disorders was, however, low and confidence intervals were not significant. Other maternal autoimmune disorders were not associated with paediatric inguinal hernias.
Table 2.
Association between maternal inguinal hernia or connective tissue disorders with risk of paediatric inguinal hernias
| Total no. of children | No. with inguinal hernia | Incidence rate per 10 000 person-years | Hazard ratio |
||
|---|---|---|---|---|---|
| Unadjusted | Adjusted * | ||||
| No maternal disorder | 765 934 | 6579 | 10.9 (10.7, 11.2) | 1.00 (reference) | 1.00 (reference) |
| Maternal inguinal hernia | 4437 | 107 | 31.2 (25.8, 37.7) | 2.84 (2.32, 3.48) | 2.92 (2.39, 3.58) |
| Maternal connective tissue disorder | |||||
| Any | 4845 | 60 | 15.6 (12.1, 20.1) | 1.44 (1.11, 1.87) | 1.30 (1.00, 1.68) |
| Rheumatoid arthritis | 1441 | 17 | 15.1 (9.4, 24.2) | 1.38 (0.86, 2.22) | 1.26 (0.78, 2.04) |
| Systemic lupus erythematosus | 760 | 10 | 16.7 (9.0, 31.1) | 1.54 (0.84, 2.84) | 1.16 (0.62, 2.15) |
| Psoriasis | 1499 | 17 | 14.1 (8.8, 22.6) | 1.31 (0.77, 2.21) | 1.25 (0.74, 2.11) |
| Other connective tissue disorder | 1453 | 19 | 16.5 (10.5, 25.9) | 1.53 (0.98, 2.38) | 1.34 (0.86, 2.11) |
| Other autoimmune disorder | 12 035 | 129 | 13.6 (11.5, 16.2) | 1.25 (1.05, 1.49) | 1.06 (0.88, 1.26) |
Values in parentheses are 95 per cent confidence intervals.
*Hazard ratio for maternal disorders versus no maternal disorder, adjusted for maternal age, maternal co-morbidity, parity, infant sex, multiple birth, preterm birth, socioeconomic deprivation, and time interval.
Children whose mothers had inguinal hernias had a greater risk of presenting with bilateral inguinal hernias (Table 3). Maternal hernias were associated with 2.84 (2.28 to 3.54) times the risk of unilateral and 3.50 (2.16 to 5.67) times the risk of bilateral paediatric hernias. The results were similar for maternal connective tissue disorders, but not significant; the HR was 1.25 (0.94 to 1.67) for unilateral hernias and 1.52 (0.84 to 2.76) for bilateral hernias.
Table 3.
Association between maternal inguinal hernia or connective tissue disorders with unilateral and bilateral paediatric inguinal hernias
| Unilateral inguinal hernia |
Bilateral inguinal hernia |
|||||
|---|---|---|---|---|---|---|
| No. of children with inguinal hernia | Incidence rate per 10 000 person-years | Hazard ratio * | No. of children with inguinal hernia | Incidence rate per 10 000 person-years | Hazard ratio * | |
| No maternal disorder | 5708 | 9.5 (9.2, 9.7) | 1.00 (reference) | 871 | 1.4 (1.3, 1.5) | 1.00 (reference) |
| Maternal inguinal hernia | 90 | 26.3 (21.4, 32.4) | 2.84 (2.28, 3.54) | 17 | 4.9 (3.0, 7.9) | 3.50 (2.16, 5.67) |
| Maternal connective tissue disorder | ||||||
| Any | 49 | 12.8 (9.7, 16.9) | 1.25 (0.94, 1.67) | 11 | 2.8 (1.6, 5.1) | 1.52 (0.84, 2.76) |
| Rheumatoid arthritis | 14 | 12.4 (7.4, 21.0) | 1.23 (0.73, 2.08) | <5 | 2.6 (0.9, 8.2) | 1.44 (0.46, 4.51) |
| Systemic lupus erythematosus | 8 | 13.4 (6.7, 26.8) | 1.13 (0.57, 2.26) | <5 | 3.3 (0.8, 13.3) | 1.27 (0.31, 5.11) |
| Psoriasis | 14 | 11.6 (6.9, 19.6) | 1.20 (0.69, 2.10) | <5 | 2.5 (0.8, 7.6) | 1.50 (0.49, 4.64) |
| Other connective tissue disorder | 15 | 13.0 (7.9, 21.6) | 1.26 (0.76, 2.09) | <5 | 3.4 (1.3, 9.2) | 1.77 (0.66, 4.72) |
| Other autoimmune disorder | 102 | 10.8 (8.9, 13.1) | 1.00 (0.82, 1.22) | 27 | 2.8 (1.9, 4.1) | 1.32 (0.89, 1.95) |
Values in parentheses are 95 per cent confidence intervals.
*Hazard ratio for maternal disorders versus no maternal disorder, adjusted for maternal age, maternal co-morbidity, parity, infant sex, multiple birth, preterm birth, socioeconomic deprivation, and time interval.
Having a maternal history of inguinal hernia was more important for the development of paediatric hernias in girls (Table 4). Girls whose mothers had inguinal hernias had 5.34 (3.82 to 7.47) times the risk of having inguinal hernias, whereas boys had 2.36 (1.83 to 3.04) times the risk. In contrast, maternal connective tissue disorders were associated with 1.35 (1.02 to 1.79) times the risk of inguinal hernias in boys, but were not associated with any risk of hernia in girls (HR 1.06, 0.55 to 2.04).
Table 4.
Association between maternal inguinal hernia or connective tissue disorders with risk of paediatric inguinal hernias in boys and girls
| Boys |
Girls |
|||||
|---|---|---|---|---|---|---|
| No. of boys with inguinal hernia | Incidence rate per 10 000 person-years | Hazard ratio* | No. of girls with inguinal hernia | Incidence rate per 10 000 person-years | Hazard ratio* | |
| No maternal disorder | 5358 | 17.4 (16.9, 17.9) | 1.00 (reference) | 1221 | 4.1 (3.9, 4.4) | 1.00 (reference) |
| Maternal inguinal hernia | 70 | 40.8 (32.3, 51.6) | 2.36 (1.83, 3.04) | 37 | 21.6 (15.7, 29.8) | 5.34 (3.82, 7.47) |
| Maternal connective tissue disorder | ||||||
| Any | 51 | 26.2 (19.9, 34.5) | 1.35 (1.02, 1.79) | 9 | 4.7 (2.5, 9.1) | 1.06 (0.55, 2.04) |
| Rheumatoid arthritis | 16 | 27.7 (17.0, 45.3) | 1.46 (0.89, 2.40) | <5 | 1.8 (0.3, 12.9) | 0.40 (0.06, 2.86) |
| Systemic lupus erythematosus | 10 | 31.4 (16.9, 58.4) | 1.39 (0.74, 2.58) | 0 | ||
| Psoriasis | 14 | 23.4 (13.8, 39.4) | 1.27 (0.73, 2.23) | <5 | 4.9 (1.6, 15.3) | 1.13 (0.37, 3.51) |
| Other connective tissue disorder | 14 | 24.0 (14.2, 40.5) | 1.21 (0.71, 2.04) | 5 | 8.8 (3.7, 21.2) | 1.94 (0.81, 4.67) |
| Other autoimmune disorder | 100 | 20.6 (16.9, 25.1) | 1.00 (0.82, 1.22) | 29 | 6.3 (4.4, 9.0) | 1.32 (0.91, 1.91) |
Values in parentheses are 95 per cent confidence intervals.
*Hazard ratio for maternal disorders versus no maternal disorder, adjusted for maternal age, maternal co-morbidity, parity, multiple birth, preterm birth, socioeconomic deprivation, and time interval.
The association between maternal inguinal hernia and risk of paediatric inguinal hernia in girls strengthened with age (Fig. 1). Compared with no disorder, maternal hernias were associated with 4.47 (3.05 to 6.54) times the risk of inguinal hernia in girls at age 2 years and 7.13 (4.66 to 10.90) times at age 8 years. In contrast, the association between maternal hernia and inguinal hernia in boys weakened over time and became non-significant at 9 years (HR 1.74, 0.89 to 3.41). Maternal connective tissue disorders were associated with inguinal hernias in boys only before 3 years of age.
Fig. 1.
Association between maternal inguinal hernia or connective tissue disorders and paediatric inguinal hernia according to age and sex
Effect of maternal inguinal hernia in a boys and b girls; effect of maternal connective tissue disorders in c boys and d girls. Hazard ratios with 95 per cent confidence intervals are shown for maternal disorder versus no maternal disorder, adjusted for maternal age, maternal co-morbidity, parity, infant sex, multiple birth, preterm birth, socioeconomic deprivation, and time interval.
In sensitivity analyses, there was no evidence that preterm birth was responsible for the association between maternal risk factors and paediatric inguinal hernia (Table S2). After excluding preterm births, children whose mothers had inguinal hernias had 3.01 (2.41 to 3.76) times the risk of inguinal hernia compared with children whose mothers had no maternal disorder. Moreover, maternal connective tissue disorders were associated with 1.44 (1.07 to 1.94) times the risk of paediatric inguinal hernia. In analyses excluding children whose mothers had both inguinal hernias and connective tissue disorders, maternal inguinal hernia remained associated with the risk of paediatric inguinal hernia (HR 2.89, 2.35 to 3.55), although associations with maternal connective tissue disorders became non-significant (HR 1.26, 0.97 to 1.65). Children with a maternal history of both inguinal hernia and connective tissue disorders had 6.95 (1.77 to 27.30) times the risk of inguinal hernia relative to children whose mothers had no disorder.
Discussion
In this study of 786 322 children with 6.2 million person-years of follow-up, children with a maternal history of inguinal hernia or connective tissue disorders had an increased risk of inguinal hernia up to 13 years of age. Compared with no maternal disorder, a history of maternal inguinal hernia was associated with 2.92 times the risk of paediatric inguinal hernia. Maternal inguinal hernia was more strongly associated with hernias in girls than in boys, whereas maternal connective tissue disorders were associated with the risk of inguinal hernia in boys only. The findings suggest that the pathophysiology of inguinal hernia may differ in girls and boys, with connective tissue pathways being potentially more important for boys. Although more research is needed to confirm these findings, clinicians should be aware that maternal characteristics may be important risk factors for paediatric inguinal hernia. Inguinal hernia should be included in the differential diagnosis of children with abdominal symptoms who have a maternal history of inguinal hernia or connective tissue disorders.
Maternal risk factors for paediatric inguinal hernias have received very little attention in the literature. Child characteristics, such as sex, prematurity, cryptorchidism, and connective tissue diseases (for example, Ehlers–Danlos syndrome), are established risk factors3, but the risk of inguinal hernia is poorly understood for other maternal characteristics. Most studies limited their attention to the clustering of inguinal hernia in families, without assessing specific maternal exposures5,6,26,27. The exception is a Danish study7 of 408 381 children in which a maternal history of groin hernia repair was associated with 2.89 times the risk of paediatric inguinal hernia. Paternal groin hernia was associated with 1.75 times the risk. In addition, maternal hernias were strongly associated with inguinal hernia in girls, with a rate ratio of 6.01 relative to no maternal hernia7. In the present study, girls whose mothers had an inguinal hernia had a very strong risk of hernia, up to 5.34 times greater. The association was weaker in boys, with a HR of 2.36.
The association between maternal inguinal hernia and hernia in girls supports the possibility of a genetic sex-linked component. Sex-related inheritance has been observed in familial studies of hernia, where associations are stronger between sisters (relative risk 17.8) than brothers (relative risk 5.8) or brothers and sisters (relative risk 3.7–4.3)5. It may be that women who have had surgery for inguinal hernia are more attentive to signs and symptoms of hernia in their children, particularly daughters. Symptomatic non-palpable inguinal hernias are rarely diagnosed in females28, but mothers with previous hernias may be more likely to have daughters with symptomatic hernias examined by a specialist.
Some of the sex variation may relate to anatomical differences between boys and girls. In boys, inguinal hernias are caused by failed closure of the processus vaginalis, which consists of an evagination of the peritoneum into the internal ring3. After elongating, the portion of the processus vaginalis above the testicle closes, obliterating the internal inguinal ring3. In girls, the mechanism relates to failed closure of the canal of Nuck, the analogue of the processus vaginalis2,3. Slight differences in the embryological development of inguinal hernias in boys and girls may explain why associations varied by sex and age. Boys with a maternal history of inguinal hernia had a higher risk of inguinal hernia early in childhood, whereas girls had a greater risk as they got older. It is also possible, however, that girls are diagnosed later owing to a generally lower incidence of inguinal hernia3. It has been reported that clinicians have more difficulty diagnosing inguinal hernia in girls28.
This study found a higher risk of inguinal hernia in boys with a maternal history of connective tissue disorders, especially rheumatoid arthritis, and possibly systemic lupus erythematosus. Although paediatric inguinal hernias are most frequently attributed to failed obliteration of the processus vaginalis3, pathological connective tissue architecture may also contribute8,9. Adults with inguinal hernia have increased synthesis of type III collagen29. As type III collagen is thinner and more immature than type I, an imbalance in the ratio of these two collagen types may weaken aponeurotic tissues and lead to inguinal hernias in older patients30. Rheumatoid arthritis and systemic lupus erythematosus are autoimmune disorders associated with inflammation of connective tissues31,32. Children of women with these connective tissue disorders may inherit connective tissue architecture that predisposes to herniation. This study found no association with autoimmune diseases not classified as connective tissue disorders, which supports such a mechanism. It remains unclear why girls were not as affected by maternal connective tissue disorders as boys. Future researchers should be aware that risk factors for inguinal hernia may differ with sex, and that non-traditional risk factors may be present in boys.
Up to 30 per cent of children who are born preterm have inguinal hernias at birth33, but preterm birth did not explain the associations in this study. Maternal hernias and connective tissue disorders remained associated with paediatric inguinal hernia even when preterm births were excluded. Hernias in preterm children, although common, have a physiological explanation and may relate less to maternal risk factors2,33. Hernias in children born at full term are more likely to have differing aetiologies that relate more closely to maternal factors.
Although a large cohort of about 800 000 children was analysed, this study has some limitations. Administrative hospital data were used and coding errors may have led to non-differential misclassification of exposures or outcomes. The data do not contain information on patients with untreated inguinal hernias. It was, moreover, not possible to distinguish direct from indirect hernias. These two types of hernia have different pathophysiology and their association with maternal characteristics may be different. Inguinal hernias among children tend to be indirect3. Associations with rare connective tissue disorders could not be investigated owing to lack of power. Future studies with larger sample sizes will be needed to investigate risks in very or extremely preterm infants. The data set does not contain information on inguinal hernias in fathers. The data lack information on potential confounders associated with autoimmune disease, and residual confounding cannot be ruled out. The data are representative of a large multicultural Canadian province, but may not be generalizable to other settings.
In this study, children with a maternal history of inguinal hernia or connective tissue disorders tended to have a higher risk of developing inguinal hernias. Having a maternal history of inguinal hernia was associated with the risk of inguinal hernia in girls, whereas maternal connective tissue disorders were associated with inguinal hernia in boys. The findings suggest that inguinal hernia is likely inherited from mothers to daughters, and that maternal connective tissue disorders may be a marker of weakened connective tissue within the inguinal canal in boys.
Supplementary Material
Acknowledgements
Data used for this study is available from the Institut de la statistique du Québec (https://statistique.quebec.ca/research/#/accueil). The statistical code used for analysis may be obtained from the corresponding author by e-mail. This research was not preregistered in an independent institutional registry.
Funding
This work was supported by grant PJT-162300 from the Canadian Institutes of Health Research, grant 6D02363004 from the Public Health Agency of Canada, and career award 34695 from the Fonds de recherche du Québec-Santé.
Disclosure. The authors declare no conflict of interest.
Supplementary material
Supplementary material is available at BJS online.
Contributor Information
Nathalie Auger, University of Montreal Hospital Research Centre, Montreal, Quebec, Canada; Institut national de santé publique du Québec, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal Quebec, Canada.
Francesca del Giorgio, Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal Quebec, Canada.
Annie Le-Nguyen, Division of General Surgery, University of Montreal, Montreal, Quebec, Canada.
Marianne Bilodeau-Bertrand, Institut national de santé publique du Québec, Montreal, Quebec, Canada.
Nelson Piché, Division of Paediatric Surgery, Sainte-Justine Hospital Centre for Children, University of Montreal, Montreal, Quebec, Canada.
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