Interpretation
In Poland, before implementing ultrasonography, the DDH rate was relatively high 6.80% and the dislocation was reported in 1.06% of the population [24]. It can be speculated that the high DDH rate was due to different diagnosis methods at the time, and only suspected infants had undergone the diagnostic process. Using the ultrasound screening, DDH was diagnosed in 5.60% of the newborns in the first week of life (Łódź, Poland) [25]. In our study, the occurrence of DDH in the university hospital in the capital city (Warsaw, Poland) during the first screening visit was lower – 4.57% than in the beforementioned study. This difference is probably due to the hip maturation curve and visit timing 1 week vs. median of 8 weeks. The DDH diagnosis can depend on the timing of the examination and the method used. As a child grows older, the hip joint matures, which can be observed with both ultrasound (α angle) and radiographs (Acetabular Index, Acetabular Depth Ratio) [20, 26].
Our work confirmed some of the already known risk factors such as female gender, breech position, cesarean section, abnormal findings in the physical examination, and positive family history of DDH. However, according to the literature, there was not even one risk factor in up to 73 - 95% of DDH cases. Also, most children with risk factors do not develop DDH, and the disease can be observed only in 1 - 10% of cases [27–30]. In contrast to these results in our study, 96.83% of DDH had at least one statistically significant risk factor.
The female gender is considered one of the most important risk factors of DDH [31]. We can find 2.4 -9.2 (OR) statistics in the available literature when comparing females to males [27]. This strong relationship was also confirmed in our study 7.11 (OR). This phenomenon is still under investigation, and the mechanism of this connection remains unclear. Various theories explain it - the most common is the gender-dependent influence of hormones, particularly relaxin, on hip joint development. Relaxin is a polypeptide hormone produced by the corpus luteum, endometrium, decidua, and placenta [32]. It has an inhibitory effect on uterine muscle contractions and relaxing on the pubic symphysis during labor. The role of relaxin, present in the blood serum, ultimately stimulates collagen turnover by increasing the secretion of matrix metalloproteinases (MMPs), collagenase and a plasminogen activator [27]. Yamasato et al. confirmed a higher expression of relaxin receptors in the placenta of the female fetus [33]. Another study by Dragooet et al. revealed that the female sex is also associated with higher relaxin receptor expression in the anterior cruciate ligament [34]. The recent reports from Ayanoget et al. confirm the association of DDH and the number of relaxin receptors in the ligament of the femoral head. However, the study does not report the difference in receptor expression depending on infant gender [35]. Although the function of relaxin is already known, there is no evidence in the literature that this mechanism of hip joint laxity is exclusively responsible for the higher frequency of DDH in females. What is more, some studies have demonstrated opposite results – lower level of the hormone in umbilical blood and higher risk of DDH [36] Given the above, some researchers have theorized that other maternal factors, such as poorer preparation of a mother's delivery canal, may also play a role, but this does not fully explain the significant prevalence of DDH in females [37].
There is also a whole group of so-called mechanical factors, in which there is pressure on the hip joint during pregnancy by the uterus walls or by the delivery canal tract at birth. One of the mentioned factors is the abnormal position and presentation of the fetus. Many authors have already described breech positioning as a risk factor. Andersen et al. advocated that neonate in a breech-presenting position in the fetal state have exerted a significant stretching force on the hip joint capsule, thus causing hip instability [38]. According to Dezateux et al. complete breech vaginal delivery (3% of all births) links with a 17- fold increased risk of DDH (OR = 17.15; CI 95% 2.79 - 22.99), while breech presentation resolved by Caesarean section relates to ten times increased risk (OR = 10.03; CI 95% 8.58 -11.72) [31]. These findings were confirmed in metanalysis (35,139 infants) by Panagiotopoulou et al. [39]. Therefore, breech positioning is probably an important risk factor of DDH during pregnancy and birth when significant forces are applied to the hip joint [40]. Our results appear to be consistent with the existing literature. We recorded 217 (5.55%) babies in the breech position, of whom 28 developed DDH, which is over 12.90% (OR = 3.65; CI 95% 2.38 - 5.62).
All authors describe abnormalities on physical examination as a risk factor - which was also unquestionably demonstrated in our study. We considered the following as abnormalities: positive Ortolani/Barlow test and/or hip joint abduction asymmetry 20 degrees or more and abduction of the joint less than 45 degrees, which is consistent with the available evidence. Some patients do not present any abnormalities on clinical examination, but an ultrasound examination reveals dysplasia. In our study abnormalities on physical examination predisposed to DDH diagnosis with OR = 25.76 (CI 95% 11.21- 59.13)
Available scientific knowledge indicates that positive family history is one of the most important risk factors of DDH [27]. According to the consensus of the Committee on Quality Improvement, Subcommittee on Developmental Dysplasia of the Hip, a risk of DDH was defined as 6% in cases of healthy parents and recognized DDH in siblings, 12% in cases of confirmed DDH of the mother/father and 36% in cases where DDH was recognized in one parent and a brother/sister. The correlation was also confirmed in our findings [41]. Authors state that higher risk can also be observed if the disease was recognized in a first-degree cousin of the child. In those cases, the risk is specified at a level of 1.7% [28]. Until recently, it was believed that individual genes are responsible for malfunctions in the physiology of connective tissue or proteins of the joint capsule. A hypothesis of a two-gene system in DDH inheritance has also arisen in literature. However, new, more progressive methods for studying molecular biology have led to further findings. We are now familiar with more than a dozen DDH-associated genes and their locations. For Caucasians, these include IL-6 and TGF-β1 genes mutations, for Asian populations: COL3A1, DKK1, HOXB9, HOXB9, HOXD9, WISP3. Non-location-specific genes mutations were also found: COL1A1, CX3CR1, GDF-5 and PAPPA2. At present, research is managing to identify individual genes in specific populations - unfortunately, at this time, we do not know the individual genes that may be involved in DDH for the world population [42]. At present, researchers are attempting to determine the exact mechanisms by which these genes may be involved in the development of DDH. No differences in a higher frequency of DDH were found in genetic disorders like Ehlers-Danlos or Marfan’s syndrome [43].
Some studies investigate the mode of delivery as potential risk factor of DDH, but the results are inconclusive. In metanalysis by L. Ortiz-Neira et al. two studies indicated that vaginal delivery could be a risk factor of DDH, and one study suggested the opposite. The results of the fourth study were inconclusive. The metanalysis of the beforementioned studies resulted in non-significant influence [44]. In our study caesarean section was associated with high DDH rate (OR = 1.43; CI 95% 1.07-1.92; p=0.016). However, cesarean section is related to a very high rate of breech position (13.5%; n = 196), which is a significant risk factor of DDH. The mode of delivery is most likely not a risk factor itself. After excluding breech delivered infants, cesarean section was not a significant risk factor of DDH (OR=1.12 CI 0.81-1.55; p>0.05).
We also examined MuP as a potential risk factor in our publication. Although the results of our study do not indicate a direct correlation, there is some evidence in the literature that the relationship could be significant for the female gender. According to Dezateux et al., special attention should be paid to MuP, especially when the children's gender is female; congenital joint hypermobility was observed in 70% of those cases [31].
Some authors consider the presence of congenital diseases as one of the DDH risk factors. Congenital Muscular Torticollis (CMT) can be associated with an increased risk of DDH to a level of 17%. Significant differences in correlations were also observed by gender - a fivefold increase of hip joint dysplasia was observed in male newborns with coexisting CMT compared to female newborns with CMT [27]. Some publications indicate Congenital Foot Deformities: as a possible risk factor for DDH. It has been shown that Talipes Calcaneovalgus or Metatarsus Adductus may be associated with an elevated risk (at the level of 4-6% and 4%, respectively). However, no connection between Talipes Equinovarus (TEV) and DDH was revealed in available data [28]. This relationship was not confirmed among our patient group.
In our study preterm delivery (37 < week) decreased risk of DDH (OR= 0.17 CI 95% 0.04-0.70). The theory explaining this phenomenon is shorter exposure to maternal hormones and lack of mechanical problems with intrauterine leg movement. Similar results were obtained in the study by Lange et al. [45] and data from the Swedish Medical Birth Register [46].
The literature indicates that most ultrasonography-diagnosed dysplastic hips are normal in clinical examination (71.63%) [11]. Similarly, only 12 out of 221 treated for DDH had a positive physical examination in our study (5,43%). Probably due to strict criteria of 20o of abduction angle difference vs. contralateral side and characteristics of the cohort – first clinical screening with physical examination upon birth. Neonates with positive Ortolani and Barlow signs are directed directly to dedicated wards after the birth.
Other risk factors, sometimes raised in scientific discussions, appear to be statistically insignificant in most studies. We examined some of them (i.e., Apgar Score <10, oligohydramnios, fetal macrosomia, parity, post-term pregnancy). Our results are consistent with the worldwide results (included in supplementary file).
Sahin F et al. highlighted that the negative predictive value of DDH risk factors combined with physical examination is high and calculation of patient’s risk could be used as a decision tool for ultrasound screening [47]. Similarly, Woodacre et al. proposed to modify the UK screening program by calculating risk for each child [48]. Roposch et al. proposed the first DDH risk calculator based on analysis of selectively screened patients in the British population. Female gender, family history, physical examination and birthweight were taken into consideration. The model demonstrated excellent discrimination and calibration of observed and predicted risk [49]. Our model was built based on universal ultrasound screening and includes risk factors from a logistic regression significant for the Polish population.