|
 |
Obstetrical Factors Governing the Etiopathogenesis of Lambdoid Synostosis
By Hrayr K. Shahinian M.D., FACS, Director, Skull Base Institute, Los Angeles; Ronald Jaekle, M.D., Assistant Professor of Obstetrics and Gynecology, Department of Obstetrics, Gynecology and Reproductive Medicine, State University of New York at Stony Brook; Richard H. Suh, M.D.; Reza Jarrahy, M.D.; Vivian C. Aguilar,M.D.; Michael Soojian M.S.
Abstract
Lambdoid synostosis results in skull deformities of varying degrees characterized by occipital flattening over the involved suture and other compensatory changes in skull shape. Such changes include contralateral occipital bossing, contralateral frontal flattening, ipsilateral frontal bossing, and ipsilateral anteroinferior displacement of the pinna (ear shearing). These deformities tend to worsen during the first year of life. The etiology has been attributed to genetic factors and primary disorders of bone growth, in addition to secondary effects of other diseases and modulators of the in utero environment. To determine causal factors in the development of lambdoid synostosis, the authors reviewed medical records of the mothers of 13 children with lambdoid synostosis who were treated at the University Medical Center of the State University of New York at Stony Brook. Pre and perinatal events, prior obstetrical, gynecological, medical, social and family histories were considered. Births of normal infants immediately prior to and just after the affected babies were born were selected as controls. There is a significant association between increased duration of the first stage of labor and the development of lambdoid synostosis. Furthermore, our results indicate that this condition has a predilection toward male infants, and may be associated with preterm labor.
Introduction
The craniosynostoses are disorders characterized by premature fusion of the cranial sutures. Growth of the fetal brain and cranium around fixed sutures results in skull deformities which vary in appearance according to the sutures involved. Patients generally present with various skull deformities and after initial evaluation are diagnosed with posterior plagiocephaly. The diagnosis can be further refined when the clinical exam is supplemented by radiographic studies and a review of the pathologic specimen. Lambdoid synostosis refers to premature fusion of the lambdoid suture in particular. This suture serves as an interface between the parietal and occipital bones and the basicranium; growth of these bones occurs along the suture line and is compromised in synostosis.1-5 Decreased bony growth along the lambdoid suture manifests in a flattening of the parietal and occipital areas on the affected side. Varying degrees of other skull deformities accompany this flattening. These deformities may include bulging (bossing) of the contralateral occipital area, bossing of the ipsilateral frontal area, flattening of the contralateral frontal area, and ipsilateral anterior and inferior displacement of the ear (i.e., shearing).3,6,7
In up to 5% of cases, children with lambdoid synostosis may have developmental delays, such as being unable to roll from a supine to a prone position.5 The etiology of these delays remains unclear. Older children with lambdoid synostosis (i.e., those greater than 9 months of age) may occasionally demonstrate an unexplained irritability.5 In some cases of extreme deformity, evidence of local areas of increased intracranial pressure may be documented on CT scan. In these cases, the severity of deformity often correlates with the degree of pressure change noted on CT.5 The majority of children with lambdoid synostosis, however, are neurologically intact and show no evidence of associated symptoms. In fact, the most common complaints at presentation are abnormal head circumference relative to standard growth curves and a persistent posterior skull deformity originally thought to represent positional molding.5 Diagnosis is made by taking a thorough history from the parents, performing a complete physical exam, and supporting these with imaging studies, including radiographic skull series and computed tomography of the head. The diagnosis of lamdoid synostosis is made after a review of the pathologic specimen.
Once a diagnosis is made, therapeutic approaches to lambdoid synostosis may be conservative or aggressive. Options include observation of the deformity and its progression, non-invasive management with helmet therapy, or surgical reconstruction of the deformed cranium.6,7,8 When surgery is preferred, early intervention is indicated: more extensive procedures may be needed to achieve desired results if the surgery is delayed until after six months of age6 In the absence of any intervention the skull deformity generally worsens during the first year of life. The deformity can become quite striking; if left untreated it may very likely contribute to the development of social and psychological problems later in life.
While cause-and-effect relationships have not been definitively proven, documented etiologies of the craniosynostoses have implicated genetic factors, primary defects of the mesenchymal blastema and of skull base growth, maternal metabolic and hematological disorders, use of cocaine or tobacco during pregnancy, fetal exposure to teratogens, fetal brain malformations (e.g., microcephaly, holoprosencephaly), hypovascularity of the fetal skull, and in utero head constraints.1,2,4,6,9-22
Although lambdoid synostosis has traditionally accounted for a small percentage of the entire spectrum of the craniosynostoses, recent studies suggest an increase in their incidence.6 Conceivably, this may be due to recent popular adaptation of supine positioning as a preventive measure against SIDS. Some authors5,6 attribute this trend to added awareness and more aggressive work-up of occipital deformities by parents, family practitioners, and pediatricians.
In this study, we review the records of the mothers of 13 children with lambdoid synostosis treated at our institution to determine which prenatal and perinatal factors demonstrate a causative relationship to its development.
Case Material: Patient Population
During the period lasting from December 1983 to May 1995, thirteen children ranging in age from 4 to 11 months underwent corrective surgery for craniosynostosis at the University Medical Center at Stony Brook. History, physical exam, and radiological studies revealed isolated right lambdoid synostosis in 10 of these 13 children. Isolated left lambdoid synostosis was found in one child, while in another involvement of the lambdoid sutures was bilateral. In one child, right lambdoid and partial left coronal synostoses were coexistent.
Seven patients were born at the University Medical Center at Stony Brook. 6 were born at outlying community hospitals for which our institution provides tertiary care and referral services.
All patients underwent complex repair of the defect, including elevation, reshaping and repositioning of parietal and occipital bone flaps. The necessity for additional procedures, such as reshaping of the frontal bones or dural plication, was determined at the time of surgery on a case-by-case basis. The diagnosis of lambdoid synostosis was confirmed after analysis of the presenting physical exam, radiographic studies and the pathologic specimens obtained at the time of operative repair.
Data Collection and Analysis of Maternal Records
Each mother was matched with two controls on the basis of a temporal relationship between delivery times: women who gave birth just prior to and just following the births of our patients were chosen as controls. None of the children of these control mothers had lambdoid synostosis. All charts were then reviewed for comparison of past obstetrical and gynecological, medical, social, and family histories, prenatal histories (including progress of the pregnancy as documented by ultrasound examination, results of routine prenatal laboratory studies, and incidence of preterm labor), and perinatal events (including admitting diagnosis, estimated gestational age of the fetus at delivery, mode of and fetal position at delivery, duration of labor, gender and birth weight, one-and five-minute apgar scores, placental pathology and other perinatal complications). Pearson's chi square, Fisher's exact 2-tail, or t-test analyses were used, where appropriate, to determine any statistically significant differences between results in control and case groups.
Results: Summary of Children's Cases
The mean age of children with lambdoid synostosis at initial presentation to the surgeons was 6.7 months (range 4 to 12 months) (Table 1). 11 of the 13 children (85%) were male. In 100% of cases, the chief complaint at this initial visit was a progressive skull deformity present since birth.
In addition to documentation of suture involvement, the occurrence of compensatory changes in skull shape in these children was recorded. Ear shearing and frontal bossing were noted for side of involvement and degree of severity. A total of 6 children (46%) exhibited some degree of ear shearing on the right side. 9 children (70%) demonstrated some degree of frontal bossing.
Torticollis was seen in 5 of 13 cases (38%). In four cases, the defect was on the right side, with one of these cases revealing bilateral involvement. There was one case affecting the left side.
The mean age at the time of surgery was 7.3 months. In all cases, surgery involved complex repair of the fused suture and deformed skull. The extent of the procedure varied on a case-by-case basis, but in general involved biparietal and occipital craniotomies where the bone flaps were elevated from the dura, reshaped, and repositioned in such a way so as to provide the skull with a more symmetrical contour. In some cases dural plication, barrel stave osteotomies, fronto-orbital advancement, or microplating were implemented.
Results: Maternal Cases and Controls:
The mean maternal age in our case group was 29.8 years (range 19-38) (Tables 2 and 3). The mean age of mothers in the control group was 27.6 (range 19-38). Mean gravidity and parity of case mothers were 2.8 and 1.1, respectively; those of control mothers were 3.0 and 1.3.
Prior birth histories between case and control groups were similar. There were no significant differences between the two groups regarding histories of infertility or its treatment. Nor did past gynecological histories differ significantly between groups, including those pertaining to sexually transmitted diseases.
No major medical or surgical histories were documented in the records of case mothers, including metabolic or hematological disease. Of interest, one control mother had Graves disease, for which she was being treated with propothiouracil and propranolol, and another had a history of idiopathic thrombocytopenic purpura.
Tobacco use during pregnancy was documented in approximately 40% of case mothers. Another 8% reported the use of cocaine during pregnancy. Details regarding these histories, such as quantity or overall duration of use, were not documented in the medical records. Nor were any efforts make to correct for a predictable26 incidence of under reporting of substance abuse. Comparisons of the available data revealed no significant differences between cases and controls.
There was no documented family history of craniosynostosis in any of the case or control mothers.
No significant differences were noted when results of routine prenatal laboratory studies (VDRL serology, gonococcal culture, chlamydia culture, rubella immunity, Hepatitis B surface antigen) were compared. Incidence of other prenatal variables, such as preeclampsia, gestational diabetes, ovarian cysts, positive culture for group B streptococcus, and elevated alpha-feto protein levels was not shown to be significant; nor were miscellaneous prenatal parameters, such as a history of pubic symphysis separation in one case.
All mothers in the case group received at least one ultrasound examination during prenatal care. However, administration of these exams and documentation of results varied according to where they were performed. Sonograms were done either by staff radiologists at our institution, by clinical faculty in the Department of Obstetrics and Gynecology, by radiologists in private practice or by radiologists at community health care clinics. Inconsistencies in the recording of results prevented us from comparing ultrasound records between case and control groups for evaluation of fetal position, size, anomalies or intrauterine fluid volume levels throughout gestation.
There was a significant difference in the incidence of preterm labor in case and control mothers (P < .10). Four mothers (31%) in the case group were documented to have preterm labor. This was markedly greater than the 9% rate of preterm labor in controls. (Preterm labor was defined as the onset of regular uterine contractions at any estimated gestation age less that 37 weeks.) In three of these cases (23%), mothers had premature rupture of membranes with subsequent onset of labor pains; they were admitted to the hospital and their babies delivered at a mean estimated gestational age by last menstrual period of 35.8 weeks. In the fourth case, uterine contractions occurred at approximately 26 weeks gestation. This episode resolved following treatment with intravenous hydration. All of these children were in vertex presentation at birth and were born either via normal spontaneous or vacuum assisted vaginal delivery. Interestingly, one of the women who labored preterm was carrying twins; fetal progress was followed throughout gestation with serial ultrasound exams. Demise of one twin was documented by sonogram at approximately 35 weeks. At that point fluid volume for the viable twin was characterized by severe oligohydramnios; this twin was in vertex position at the time. All of the remaining children born with lambdoid synostosis were term babies.
The mean duration of the first stage of labor was nearly three times greater among case mothers when compared to controls: mothers giving birth to babies with lambdoid synostosis labored for at least an average of 597 minutes (range 75 to 1505 minutes; median 570 minutes) before full dilation and 100% effacement, versus an average of 221 minutes in controls (range 30 to 540 minutes; median 150 minutes). This result is highly significant (P < .01). The power of statistical analysis of this difference is greater than 75%. These times underestimate the actual duration of this stage of labor, as the medical records only provide notation on "inpatient" labor: in all cases, labor pains began outside of the hospital and progressed for variable periods of time before the mothers were admitted and documentation of labor began.
Length of the second stage of labor did not significantly vary between case and control groups. As records of the length of the third stage of labor were incomplete, it was not included in the analysis of labor progress.
Another significant difference (P < .10) between case and control groups was in the gender distribution of births. Children born with lambdoid synostosis were male in 84.6% of cases, compared to an incidence of male births in 57.7% of controls.
Discussion
Often, the parieto-occipital flattening that occurs in lambdoid synostosis is misinterpreted as a normal consequence of childbirth. The cranial sutures allow for movement of the calvarial bones as the fetus descends through the pelvis and birth canal, resulting in positional molding. This physiological alteration in head shape generally resolves in the days to weeks following birth. By comparison, skull deformities due to premature fusion of the lambdoid suture persist and may become progressively worse, ultimately requiring corrective surgery.23
Recent increases in awareness and workup of posterior deformities have most likely contributed to an increased incidence of this once relatively rare phenomenon. Much subsequent research effort has been directed toward elucidating those factors which contribute to its pathogenesis. Evidence has been generated supporting hypotheses that this is an inherited disorder,4,12,13 that the deformity is the result of a primary defect in the growth of the basicranium, 20 or that a variety of metabolic and hematological diseases, toxic exposures or mechanical stressors on the fetus may play causal roles.2,9,10,18,22,24-26
The purpose of this study was to clarify which variables in the obstetrical histories of mothers demonstrate statistically relevant associations with the incidence of lambdoid synostosis in their children.
Our study benefited from a relatively large subject population: thirteen children were treated at our institution for lambdoid synostosis over the past twelve years. Furthermore, because these children were born either at the University Medical Center at Stony Brook or at local community hospitals, we were able to access maternal hospital records conveniently. This allowed us to look closely at the prenatal and perinatal periods and evaluate the contributions of several variables to the development of lambdoid synostosis. The ready availability of medical records also allowed us to control for these variables in a population of mothers who gave birth to children without lambdoid synostosis.
Our results demonstrate a significant relationship between the incidence of lambdoid synostosis and a prolonged first stage of labor. The first stage of labor is defined as the time period beginning with the onset of uterine contractions and ending with full cervical dilation and effacement. During this time the uterus contracts in periodic fashion, generating increased intrauterine pressures. These escalate in magnitude as labor progresses, facilitating the descent of the fetus through the pelvis. Duration of this stage of labor was nearly tripled in the mothers giving birth to babies with lambdoid synostosis. As discussed earlier, this ratio most likely represents a conservative estimate of the actual difference in duration of labor between case and control mothers. As the fetal head progresses rostrally, it is subject not only to elevating intrauterine pressures, but also to the more constrained architecture of the inferior pelvis. It is reasonable to assume that the cumulative deformational forces imposed upon the fetal head in this environment are exacerbated with protracted exposure to such conditions.
This finding supports the conclusion that fetal head constraint plays a role in the pathogenesis of lambdoid synostosis. Graham14,15 reports that patency of the cranial sutures is dependent on the continued transmission of growth-stretch tensile forces generated by the developing brain to the sutures via the dura mater. If the delivery of these forces to a particular suture is compromised, bone deposition in the suture line is liable to occur and premature fusion may result. Intrauterine compression of the fetal head causes such an alteration in suture tension. Compression of the parietal and occipital bones, for example, can relieve the stress imparted to the lambdoid suture, thereby interfering with the primary stimulus responsible for suture growth. Prolonged periods of uterine contraction may increase the likelihood of significant compressive forces exerting deleterious effects on the suture.
The fact that all cases but one had involvement of the right lambdoid suture proposes a model for how, in the presence of intrauterine constraint, fetal head position moderates suture involvement in craniosynostosis. In the occiput posterior position, the occipital bone is intimately related to the sacrum. Labor is often prolonged when the fetus is in this position, as contact between occipital bone and sacrum prevents smooth passage through the pelvis. When the occiput is located anteriorly, it shares a similar relationship with the pubic symphysis. Head rotation (e.g., left occiput anterior, right occiput posterior, etc.) may also bring the parietal bones into contact with these landmarks. A third potentially deformational force can be delivered in the birth canal by the spinous processes of the ischial bones. In children with right lambdoid synostosis, it is likely that the right posterior head is compressed against one of these bony structures. If the duration of labor is then increased, the chances that this contact will relieve tension in the suture and, subsequently, alter the rate of bone deposition, also increases. Unfortunately, fontanel positioning was not consistently documented during labor and delivery. Such data, if available, might reveal patterns of fetal head orientation that predict particular suture involvement with synostosis. The fact that almost all notations of torticollis were right sided in these children also supports this model, further suggesting compression of the right side of the fetal head.
Additional evidence supporting the significance of the duration of labor in developing right lambdoid synostosis is provided by the observation that there is a correlation between its incidence and the occurrence of preterm labor in our case mothers. By definition, preterm labor implies the onset of uterine contractions at any time prior to 37 weeks of gestation. Treatment depends on the maturity of the fetus: laboring mothers near term with documentation of fetal lung maturity are often delivered, while significantly premature labor in the absence of reassuring indicators of fetal viability is aggressively treated to prevent the birth of an immature infant. Preterm labor that progresses to delivery subjects the fetus to conditions similar to those seen at term: as intrauterine pressures escalate, the fetal head (assuming vertex presentation) descends into an area of more constrained volume, and greater cumulative deformational forces are exerted upon it. Preterm labor that is successfully arrested will still potentially deliver some degree of deformational injury to the fetus. Subsequent labor at term may add further insult to this injury and facilitate the development synostosis. In addition to these mechanical considerations, the biochemical changes that occur during labor also warrant mention. Labor is associated with an increase in the synthesis of prostaglandins, which also play a role in the growth and development of the cranial sutures. While no relationship is readily evident from our work, the alteration in rates of synthesis and release of uterine prostaglandins associated with the onset of labor may impact upon the prostaglandin-mediated dynamics of suture growth. Treatment of preterm labor with prostaglandin synthesis inhibitors presents yet another variable worthy of further attention in the discussion of craniosynostosis.
Whether it is undergoing labor prematurely or at full term, the ability of the fetus to adapt to the tumultuous environment of the laboring uterus is monitored via external and internal monitoring devices. These measure the periodicity and magnitude of uterine contractions, as well as the response of the fetal heart to this activity. Such monitoring is useful for detection of fetal distress secondary to excessive intrauterine pressures. "Early decelerations" refer to fetal bradycardias that temporally coincide with contraction: pressure on the fetal head results in a temporarily decreased heart rate that rebounds at the end of contraction, as this pressure is relieved. "Late decelerations," by comparison, are fetal bradycardias that occur following uterine contraction: these portend more ominous intrauterine events, such as utero-placental insufficiency. In either case, these phenomena demonstrate how the contracting uterus affects blood flow and oxygen delivery to the fetus during labor. Longer periods of labor lengthen fetal exposure to potentially critical hypoxic events. Following the work of Hinton13 and Sen22 who document correlations between cerebral hypoperfusion and craniosynostosis, we can assume that protraction of vascular and oxygen deficiencies increase the probability that lambdoid synostosis will ensue.
Fetal head constraint is dependent upon more than just uterine contractions and the volume of the lower pelvis: we must also consider what they act upon. We found a predominance of males in the population of children we treated for lambdoid synostosis. This result is consistent with the work of Graham,14 who discusses differences between rates of intrauterine head growth and head sizes. These factors render the male fetal head more vulnerable to the unfavorable conditions in the laboring uterus: by virtue of its greater size, the male head would be more susceptible to the collective deformational forces of a contracting uterus and a narrow pelvis. Similarly, a more rapid rate of growth suggests that the male head achieves greater dimensions earlier in gestation than the female head: this translates into longer exposure to the evolving intrauterine environment of constraint. The large male head, then, is at increased risk of exposure to elements that may interfere with transmission of tensile stimuli to the cranial sutures, especially when this exposure is long.
Based upon this study, the incidence of lambdoid synostosis appears to be dependent on the coexistence of multiple factors. The etiologic role of fetal head constraint in the pathogenesis of lambdoid synostosis is seen in a new light, as we now must consider temporal issues in the generation of potentially deformational intrauterine forces. Fetal head constraint plays the central mechanistic role in the deposition of bone along the suture line. The degree and nature of that constraint will vary depending on several variables. A greater fetal head size predicts greater susceptibility to any pressures that are generated within the contracting uterus; inasmuch as it correlates with larger head size, then, male gender represents a predisposition to this vulnerability. Fetal head orientation may dictate which sutures are involved. The events of preterm labor may contribute to head constraint in any of three possible ways: either as described for term labor, or by delivering an initial insult to the fetus that may be compounded at term labor, or via some prostaglandin-mediated effect upon the suture. Ultimately, however, increased duration of the first stage of labor seems to be the most significant factor contributing to head constraint. Hypoperfusion secondary to head constraint may play an adjunctive role.
Interesting issues that are raised by our results include the biochemical effects of labor on suture pathology and the dynamics of suture growth and maturity: how quickly does a suture first demonstrate signs of fusion when subject to forces that relieve the tensile forces delivered to it? These issues certainly merit further inquiry in arriving at an even more precise illustration of the critical events responsible for the occurrence of lambdoid synostosis.
References
- Cohen MM Jr: Sutural biology and the correlates of craniosynostosis. Am J Med Genet 1993;47:581-616
- Hinton DR, et al: Lambdoid synostosis, Part 1: The lambdoid suture: normal development and pathology of ‘synostosis'. J Neurosurg 1984;61:333-33
- Ohman JC, Richtmeier JT: Perspectives on craniofacial growth. Clin Plast Surg 1994;21:489-498
- Vander Kolk CA, Beaty T: Etiopathogenesis of craniofacial anomalies. Clin Plast Surg 1994;21:481-487
- Vander Kolk CA, Carson BS: Lambdoid synostosis. Clin Plast Surg 1994;21:575-584
- Muakkassa KF, et al: Lambdoid synostosis, Part 2: Review of cases managed at The Hospital for Sick Children, 1972-1982. J Neurosurg 1984;61:340-347
- Persing JA, et al: Lambdoid synostosis: surgical considerations. Plast Reconstr Surg 1988;81:852-860
- Clarren SK, et al: Helmet treatment for plagiocephaly and congenital muscular torticollis. J Pediatr 1979;94:43-46
- Alderman BW, et al: Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Teratology 1994;50:13-18
- Beeram M, et al: Occurrence of craniosynostosis in neonates exposed to cocaine and tobacco in utero. J Natl Med Assoc 1993;85:865-868
- Bruneteau RJ, Mulliken JB: Frontal plagiocephaly: synostotic, compensational, or deformational. Plast Reconstr Surg 1990;89:21-31
- Cohen MM Jr: Etiopathogenesis of craniosynostosis. Neurosurg Clin N Am 1991;2:507-512
- Cohen MM Jr, ed. Craniosynostosis: Diagnosis, Evaluation, and Management. New York: Raven Press, 1986
- Graham JH Jr: Alterations in head shape as a consequence of fetal head constraint. Semin Perinatal 1993;7:257-268
- Graham JH Jr, et al: Coronal craniostenosis: fetal head constraint as one possible cause. Ped 1980;65:995-999
- Graham JH Jr, Smith DW: Metopic craniostenosis as a consequence of fetal head constraint: two interesting experiments of nature. Ped 1980;65:1000-1002
- Haberkern CM, et al: The ‘breech head' and its relevance. Am J Dis Child 1979;133:154-156
- Higginbottom MC, et al: Intrauterine constraint and craniosynostosis. Neurosurgery 1980;6:39-44
- Lohse DC, et al: Cranial asymmetry and lambdoid synostosis in a sibship. Neurosurgery 1985;16:836-838
- Moss ML: Functional anatomy of cranial synostosis. Child's Brain 1975;1:22-33
- Sen A, et al: Technitium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis. J Nucl Med 1995;36:394-397
- Zuckerman B, et al: Effects of maternal marijuana and cocaine use on fetal growth. N Eng J Med 1989;320:762-768
- Hoffman HJ, Reddy KKV: Progressive cranial suture stenosis in craniostenosis. Neurosurg Clin N Am 1991;2:555-563
- Shuper A, et al: The incidence of isolated craniosynostosis in the newborn infant. Am J Dis Child 1985;139:85-86
- Hunter AGW, Rudd NL: Sagittal synostosis; its genetics and associated clinical findings in 214 patients who lacked involvement of the coronal sutures. Teratology 1976;14:185-194
- Riggs W Jr, et al: Neonatal Hyperthyroidism with accelerated skeletal maturation, craniosynostosis, and brachydactyly. Pediatr Radiol 1972;105:621-625
Table 1. Children's cases
Age
Gender
Ear Shearing
Frontal Bossing
Torticollis
Right
Left
Bilateral |
6.7 months
11:2 M:F
6/13 (46%)
9/13 (70%)
5/13 (38%)
3
1
1 |
Table 2. Maternal Cases
| |
Cases |
Controls |
Age
Gravidity
Parity
Preterm Labor
PROM
Labor: 1st Stage |
29.8 yr
2.8
1.1
4/13 (31%)
3 (23%)
597 min (p<.01) |
27.6 yr
3.0
1.3
9%
221 min |
Table 3. Maternal Cases
| Patient |
Age |
Gravida |
Para |
Labor (1st Stage) |
Gender of Child |
1
2
3
4
5
6
7
8
9
10
11
12
13 |
37
33
23
19
35
32
29
26
25
28
31
38
32 |
1
3
2
1
2
3
2
1
4
2
3
8
5 |
0
2
1
0
1
1
0
0
1
0
2
3
3 |
1505 min
C/S*
730 min
825 min
1020 min
210 min
1143 min
240 min
360 min
135 min
120 min
75 min
570 min |
F
M
M
M
M
M
M
M
M
F
M
M
M |
|
|
|
 |
|
