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1.

Background

It is difficult to determine whether to treat a given girl who has idiopathic central precocious puberty (CPP) with gonadotropin-releasing hormone analog (GnRHa) in terms of adult height (AH). The objective was to provide an easy tool for predicting AH and age at first menstruation at initial evaluation to help guide the decision regarding whether to treat.

Methods

Data analysis using multiple linear regression models was performed in 134 girls with CPP. Among them 78 were given GnRHa because of low predicted AH (n=45), pubertal luteinising hormone (LH)/follicle-stimulating hormone peaks (FSH) ratio (n=50) and/or high plasma estradiol concentration (n=45). 56 girls were followed without treatment.

Results

In the whole population, the actual AH (162.1±5.61 cm) was similar to target height (161.7±4.91 cm) and to AH predicted by the Bayley and Pinneau method (161.9±7.98 cm). Separated models for treated and untreated girls provide very close estimations, leading to a unique formula for both groups. The AH (cm) could be calculated at the initial evaluation: 2.21 (height at initial evaluation, SD) + 2.32 (target height, SD) – 1.83 (LH/FSH peaks ratio) + 159.68. The actual AH was lower than the calculated AH by more than 1 SD (5.6 cm) in 11 girls (8.0%). The time between onset of puberty and first menstruation (in untreated girls) can be estimated with: 10.9 - 0.57 (LH/FSH peaks ratio). The formulae are available at http://www.kamick.org/lemaire/med/girls-cpp15.html.

Conclusions

We established formulae that can be used at an initial evaluation to predict the AH, and the time between onset of puberty and first menstruation after spontaneous puberty. The similarity of the formulae for both groups suggests that the treatment had no significant effect on the AH. However, the criteria used to select treatment suggest that it prevents the deterioration of AH in cases with rapidly evolving form of CPP.  相似文献   

2.
《Endocrine practice》2019,25(7):717-728
Objective: The optimal treatment for girls with central precocious puberty (CPP) is unknown. We conducted a network meta-analysis to evaluate the efficacy and safety of existing treatments to provide credible clinical guidelines.Methods: We compared gonadotropin-releasing hormone analogue (GnRHa) therapy, GnRHa plus growth hormone (GH) combination therapy, and no-treatment therapy for girls with CPP by performing an electronic search for studies in PubMed, Embase, Chinese National Knowledge Infrastructure databases, and Wanfang Data from their inception until September 30, 2018. Six outcomes, including bone maturation ratio, final height, final height compared with target height, growth velocity, height gain, and gain in predicted adult height (ΔPAH), were expressed as the mean difference with 95% confidence interval. The surface under the cumulative ranking curve (SUCRA) value illustrated the rank probability of each treatment under different outcomes.Results: Twenty-two studies with 1,268 patients were included. GnRHa plus GH had the best performance on final height, final height compared with target height, growth velocity, height gain, and ΔPAH, with the highest SUCRA values of 0.919, 0.975, 0.909, 0.999, and 0.957, respectively. For bone maturation ratio, GnRHa ranked the highest, with a SUCRA value of 0.663. No severe adverse effects were reported.Conclusion: For girls with CPP, GnRHa plus GH had the highest probability of being the optimal therapy for improving final height, and no severe adverse effects were reported.Abbreviations: BMI = body mass index; CI = confidence interval; CPP = central precocious puberty; GH = growth hormone; GnRHa = gonadotropin-releasing hormone analogue; HPG = hypothalamic-pituitary-gonadal; LH = luteinizing hormone; NMA = network meta-analysis; PAH = predicted adult height; PCOS = polycystic ovary syndrome; RCT = randomized controlled trial; SUCRA = surface under the cumulative ranking curve  相似文献   

3.
对收集的16例未见血液雌激素水平升高的临床女孩性早熟患者的外周血样本,利用PCR-SSCP方法筛查了雌激素受体基因编码区的可能突变。结果在1例患者发现:其雌激素受体基因8号外显子编码精氨酸的548位密码子,1个C→T转换导致精氨酸残基被半胱氨酸所替代;这一突变使DNA序列中产生1个BtsⅠ酶切位点,通过PCR-RFLP实验证明此患者为Arg548/Cys548杂合体。为证明该突变在性早熟发生中的作用,构建了一个雌激素受体反应元件报道质粒pGL3-promoter-ERE;成功将野生型ESR1基因定点突变,并克隆于PCR3.1真核表达质粒。报道质粒和表达质粒共转染CMF-7细胞,Cys548突变能够增加萤火虫荧光素酶的产生。结果证明该突变雌激素受体在体外具有高活性特征,因而推测在体内也可能具有相应的过高活性,从而导致女孩的性早熟。  相似文献   

4.
对收集的16例未见血液雌激素水平升高的临床女孩性早熟患者的外周血样本,利用PCR—SSCP方法筛查了雌激素受体基因编码区的可能突变。结果在1例患者发现:其雌激素受体基因8号外显子编码精氨酸的548位密码子,1个C—T转换导致精氨酸残基被半胱氨酸所替代;这一突变使DNA序列中产生1个BtsⅠ酶切位点,通过PCR—RFLP实验证明此患者为Arg548/Cys548杂合体。为证明该突变在性早熟发生中的作用,构建了一个雌激素受体反应元件报道质粒pGL3-promoter—ERE;成功将野生型ESR1基因定点突变,并克隆于PCR3.1真核表达质粒。报道质粒和表达质粒共转染CMF-7细胞,Cys548突变能够增加萤火虫荧光素酶的产生。结果证明该突变雌激素受体在体外具有高活性特征,因而推测在体内也可能具有相应的过高活性,从而导致女孩的性早熟。  相似文献   

5.

Background

Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children.

Methods

Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs.

Results

The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (≥6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P <0.0001).

Conclusions

The annual incidence of CPP has substantially increased among Korean girls over the past 7 years. Continued monitoring of CPP trends among Korean children will be informative.  相似文献   

6.
7.
《Endocrine practice》2012,18(6):e144-e146
ObjectiveTo report the first case of imperforate hymen and vaginal atresia in a patient with mucocolpos during toddlerhood who was found to have central preco cious puberty.MethodsWe review the details of assessment of an 18-month-old girl who had the presence of pubic hair and breast enlargement. She underwent biochemical evaluation with serum follicle-stimulating hormone, luteinizing hor mone, and estradiol and radiologic evaluation with ultra sonography of the abdomen and pelvis as well as magnetic resonance imaging of the pelvis and brain.ResultsThis young female patient had clinical and imaging findings suggestive of idiopathic central preco cious puberty. Imaging also revealed imperforate hymen, vaginal atresia, and mucocolpos. She underwent surgical treatment to ensure an unobstructed vaginal opening before initiation of gonadotropin-releasing hormone agonist ther apy, since the latter may precipitate uterine bleeding and might have converted mucocolpos to a combination of mucocolpos and hematocolpos.ConclusionThis case highlights the need to suspect the presence of precocious puberty in all female patients in whom mucocolpos is detected beyond infancy but before adolescence. (Endocr Pract. 2012;18:e144-e146)  相似文献   

8.
《Endocrine practice》2007,13(6):652-655
ObjectiveTo describe 2 cases of primary hypothy-roidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy.MethodsWe present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy.ResultsTwo patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center. Both patients presented with precocious puberty and vaginal bleeding and had undergone unilateral oophorectomy before referral. In the first patient (case 1), the surgical intervention was a consequence of torsion of the left megaovary, necessitating emergency oophorecto-my. Oophorectomy in the second patient (case 2) was a result of initial diagnostic confusion, inasmuch as a sex-cord stromal tumor was suspected. A detailed history, physical examination, and laboratory results pointed toward primary hypothyroidism due to Hashimoto’s thy-roiditis and thyroid dysgenesis, respectively. Serial ultra-sound studies of the abdomen and pelvis revealed large multicystic ovaries, with progressive enlargement (includ-ing regrowth from an apparent ovarian “postsurgical remnant”). Both patients responded dramatically after initiation of levothyroxine replacement therapy, with no further vaginal bleeding and reversal of megaovary to normal size (in case 1).ConclusionIn a highly selected minority of children with untreated primary hypothyroidism, there is development of precocious puberty and progressively enlarging multicystic ovaries. The precise endocrine, neuroanatomic, and neurophysiologic bases for this phenomenon are unclear. Nevertheless, the entire clinicopathologic picture,including giant ovaries, dramatically reverts to normal status with the restoration of a euthyroid state by means of simple levothyroxine replacement therapy. (Endocr Pract. 2007;13:652-655)  相似文献   

9.
《Endocrine practice》2012,18(4):519-528
ObjectiveTo evaluate the economic burden of central precocious puberty (CPP) by examining direct health care resource utilization and costs.MethodsAdministrative claims from the Medstat MarketScan Commercial Claims database were analyzed, and 2 cohorts of children ≤ 12 years of age were identified. The CPP cohort included patients newly diagnosed with precocious sexual development and puberty (International Classification of Diseases, Ninth Revision, Clinical Modification code 259.1x) between January 1, 2004, and June 30, 2006 (date of the initial diagnosis of CPP was designated as the “index date”) who used gonadotropin-releasing hormone agonists during the 12 months after diagnosis. Each patient with CPP was matched with 4 control patients without CPP on the basis of age, sex, geographic region, and type of health insurance plan. Resource utilization and costs during the 12 months before and the 12 months after the index date were examined.ResultsA total of 172 patients with CPP and 688 control patients were identified after matching. Approximately 62% of patients were 7 to 9 years of age, and 87% were female. The patients with CPP had higher annual health care costs than did the control patients during the 12-month pre-index ($10,968 versus $783; P < .001) and the 12-month post-index ($21,071 versus $849; P < .001) periods, primarily attributable to outpatient and pharmacy costs. For the patients with CPP, annual health care costs increased by $10,103 after diagnosis. On average, annual CPP-related costs were $10,605. Monthly total health care costs for the patients with CPP increased sharply during the first month after diagnosis and remained high throughout the postindex period.ConclusionIn this study, health care resource use and costs among patients with CPP were substantial before and after the initial diagnosis of CPP. (Endocr Pract. 2012;18:519-528)  相似文献   

10.
《Endocrine practice》2010,16(2):237-240
ObjectiveTo report a rare case of central precocious puberty attributable to hypothalamic hamartoma that was diagnosed in utero.MethodsWe present the clinical, laboratory, and imaging data pertaining to our case and discuss the diagnostic features and recommended treatment of central precocious puberty in patients with hypothalamic hamartoma.ResultsA 3-month-old male child had had excessively rapid growth velocity and weight gain since birth. On investigation, the patient was diagnosed as having hypothalamic hamartoma with central precocious puberty. On inquiry, his mother described a history of prenatal ultrasonography and fetal magnetic resonance imaging suggesting the presence of a cystic lesion in his brain at 9 months of gestation. Because of continued rapid growth and acceleration of puberty during a 4-month observation period, we decided to treat the patient with leuprolide acetate. The patient responded well to treatment, with stabilization of growth.ConclusionTo the best of our knowledge, this patient is the youngest in the medical literature diagnosed to have central precocious puberty and also to receive treatment with leuprolide acetate. (Endocr Pract. 2010;16:237-240)  相似文献   

11.
摘要 目的:探讨曲普瑞林联合小剂量生长激素物治疗女童CPP疗效及对骨龄影响。方法:选取2017年1月至2020年1月我院收治的200例CPP女童,随机将其分为两组,对照组100例,给予常规治疗,研究组100例,给予曲普瑞林联合小剂量生长激素治疗。观察两组患者的临床疗效、治疗前后血清性激素水平、子宫容积、卵巢容积变化情况以及生长发育指标变化。结果:治疗后,研究组总有效率为98 %;显著高于对照组总有效率(80 %,P<0.05)。两组FSH、LH、E2水平、子宫容积、卵巢容积均降低,骨龄、身高、PAH均显著升高,且研究组上述指标明显优于对照组(P<0.05)。结论:曲普瑞林联合小剂量生长激素物治疗女童CPP疗效显著,能很好的改善患者血清性激素水平、子宫容积、卵巢容积,对生长发育指标具有积极的意义,值得临床推广和应用。  相似文献   

12.

Objective

To examine the influence of childhood obesity on the early onset of puberty and sex hormones in girls.

Methods

Healthy girls with different percentages of body fat at baseline (40 obese, 40 normal, and 40 lean) were recruited from three elementary schools in Shenyang, China. These girls (mean age 8.5 years) were also matched by height, school grade, Tanner stage, and family economic status at baseline. Anthropometry, puberty characteristics, and sex hormone concentrations were measured at baseline and at each follow-up visit. The generalized estimating equation model and analysis of variance for repeated measures using a generalized linear model were used to determine the differences in puberty characteristics and sex hormones among three groups.

Results

Over 4 years, mean age of breast II onset was earlier among obese girls (8.8 years) than normal girls (9.2 years) and lean girls (9.3 years). The prevalence (%) of early-maturation in the obese, normal, and lean groups was 25.9%, 11.1%, and 7.4%, respectively. Obesity was associated with an increased risk for breast stage II (year 2: RR, 6.3; 95% CI, 1.9–21.1 and year 3: RR, 6.9; 95% CI, 0.8–60.1). None of the girls experienced menarche in the first year; however, by the fourth year 50.0% of obese girls had menarche onset, which was higher than normal weight (27.5%) and lean girls (8.1%). The mean estradiol level increased with age in the obese, normal, and lean groups. The mean estradiol concentration was higher in obese girls than in normal and lean girls throughout the 4-year period (P<0.05).

Conclusions

Childhood obesity contributes to early onset of puberty and elevated levels of estradiol in girls.  相似文献   

13.
摘要 目的:分析中枢性性早熟对儿童生长发育的影响及其危险因素。方法:选择我院自2020年1月至2023年1月收治的105例中枢性性早熟患儿作为观察组,另选同期的105例发育正常儿童作为对照组,比较两组生长发育指标、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白3(IGF-BP3)表达水平,对入组者膳食模式、生活情况、家庭状况进行问卷调查,使用单因素分析和多因素Logistic回归分析。结果:观察组身高、体重、身体质量指数、骨龄均大于对照组(P<0.05);观察组血清IGF-1、IGF-BP3表达水平均高于对照组(P<0.05);经单因素分析,午睡习惯、运动时间、亮灯睡觉、课业负担、经常使用塑料制品、成人洗漱护肤品、观看情感类电视、母亲学历、职业、初潮年龄,父母关系、陪伴、平衡膳食模式、高热量高脂膳食模式均与中枢性性早熟有关(P<0.05);经多因素Logistic回归分析,平衡膳食模式、有午睡习惯、运动时间长均是中枢性性早熟的保护因素(P<0.05),高热量高脂膳食模式、母亲初潮年龄小、父母关系不和睦、父母陪伴少均是中枢性性早熟的危险因素(P<0.05)。结论:中枢性性早熟可影响儿童的生长发育进度,与高热量高脂膳食模式、母亲初潮年龄、父母关系和陪伴密切相关,应改善家庭关系,帮助儿童养成平衡膳食、午睡和运动的良好习惯,有益于儿童正常的生长发育。  相似文献   

14.
《Endocrine practice》2020,26(3):267-284
Objective: Delayed puberty is a common condition, and typical management includes “watchful waiting” and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of delayed puberty in girls and boys.Methods: A national survey of pediatric endocrine providers assessed definitions of delayed puberty, practices around sex-steroid therapy, reasons for treatment, and comfort in managing delayed puberty in girls and boys.Results: Of 184 respondents (12% participation rate), 64% and 71% used the traditional age cutoffs for defining delayed puberty of 13 years for girls and 14 years for boys, respectively. Nearly half (45%) of providers would treat boys relatively earlier than girls, compared to 18% who would treat girls relatively earlier (P<.0001). Providers were more likely to cite bone density as a reason to treat girls and alleviating patient and parental distress, accelerating growth, and “jump starting” puberty as reasons to treat boys. Greater experience in endocrine practice was associated with greater comfort managing delayed puberty in both boys and girls. Approximately 80% of providers agreed that clinical guidelines are needed for the management of delayed puberty.Conclusion: There is a high degree of variability in the clinical management of delayed puberty, and our results suggest that providers are more hesitant to treat girls compared to boys and have different reasons for treating each. It remains to be determined if these discrepancies in treatment are justified by biologic differences between girls and boys or represent nonevidence-based disparities in care.Abbreviation: U.S. = United States  相似文献   

15.
16.
摘要 目的:探究知柏地黄丸治疗对中枢性性早熟(ICPP)女童卵巢容积、卵泡直径及第二性征发育的影响。方法:选取2019年2月~2021年2月于本院就诊的86例ICPP女童,随机分为对照组(n=43)和观察组(n=43),对照组给予醋酸曲普瑞林,观察组在对照组基础上给予知柏地黄丸。比较两组临床疗效、子宫容积、卵巢容积和卵泡直径、性激素水平[促卵泡激素(FSH)、雌二醇(E2)及促黄体激素(LH)]、骨代谢指标水平[Ⅰ型胶原氨基端肽(P1NP)、骨钙素N端中分子片段(N-MID)、Ⅰ型胶原羧基端肽交联(β-CTX)]及不良反应。结果:治疗后与对照组相比,观察组总有效率明显较高(P<0.05),子宫容积、卵巢容积和卵泡直径均明显较小(P<0.05),FSH、E2、LH、P1NP、N-MID及β-CTX水平均明显较低(P<0.05);两组不良反应总发生率无差异(P>0.05)。结论:知柏地黄丸治疗ICPP患儿具有较好的临床疗效,可减小卵巢、子宫的提前变化,降低性激素水平,改善骨代谢指标水平,安全性较好。  相似文献   

17.
BackgroundAplastic anemia (AA) is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.MethodsPatients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA) were treated with cyclosporine (CsA) and danazol while patients with severe AA (SAA) as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.ResultsAmong the 63 studied patients, 29 (46%) had NSAA and 34 (54%) had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01). The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.ConclusionThis long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.  相似文献   

18.
Adolescent idiopathic scoliosis (AIS) is a multifactorial disease affecting approximately 1–4% of teenagers especially girls at the age of 10–16, but its etiopathogenesis remains uncertain. Previous study has revealed that the cortical thickness in AIS patients is different from that in normal controls. Cortical thickness measurements are known to be strongly correlated between regions that are axonally connected. Hence, a hypothesis is proposed to study the possibility to demonstrate abnormal structural network revealed by cortical thickness in AIS patients. The aim of the study is to investigate abnormalities in the organization of the brain cortical network in AIS patients. This study included 42 girls with severe idiopathic scoliosis (14.7±1.3 years old) and 41 age-matched normal controls (NC, 14.6±1.4 years old). The brain cortex was partitioned into 154 cortical regions based on gyral and sulcal structure. The interregional connectivity was measured as the statistical correlations between the regional mean thicknesses across the subjects. We employed the graph theoretic analysis to examine the alteration in interregional correlation, small-world efficiency, hub distribution, and regional nodal characteristics in AIS patients. We demonstrated that the cortical network of AIS patients fully preserved the small-world architecture and organization, and further verified the hemispheric asymmetry of AIS brain. Our results indicated increased central role of temporal and occipital cortex and decreased central role of limbic cortex in AIS patients compared with controls. Furthermore, decreased structural connectivity between hemispheres and increased connectivity in several cortical regions were observed. The findings of the study reveal the pattern of structural network alteration in AIS brain, and would help in understanding the mechanism and etiopathogenesis of AIS.  相似文献   

19.
《Gender Medicine》2007,4(4):367-373
Background: Previous studies have reported gender differences in pacemaker selection.Objective: This study aimed to assess gender-related differences in pacemaker mode selection in patients undergoing their first implantation.Methods: A retrospective analysis was undertaken from a single-center database of pacemaker implants during the years 2001 to 2003. Univariate and multivariate analyses were used to compare pacemaker mode selection adjusted for any significant difference between the sexes.Results: A total of 274 pacemakers were implanted during the study period, 259 of which formed the basis of this study. Of the patients receiving pacemakers, 132 were male and 127 were female. The majority of patients (144 [55.6%]) had sick sinus syndrome as their indication for receiving a pacemaker, followed by complete heart block (75 [29.0%]), and second-degree or high-grade atrio-ventricular block (36 [13.9%]). Four (1.5%) patients had hypersensitive carotid sinus syndrome. The mean (SD) age of patients was 61.35 (15) years. Most (155 [59.8%]) patients were younger than age 65, and the women were significantly older than the men (P = 0.004). Atrial fibrillation (AF) was present in 53 (20.5%) patients. Dual-chamber (DDD) pacemakers were implanted in 196 (75.7%) patients, and single-chamber ventricular pacemakers in 63 (24.3%) patients. Significantly more DDD pacemakers were implanted in patients aged <65 years compared with those aged ≥65 years (P < 0.01). This difference was, however, primarily due to the higher rate of AF in the older patients versus patients aged <65 years. Although the rate of DDD implantations was observed to be higher among women (101/127 [79.5%]) compared with men (95/132 [72.0%]), the rate difference was nonsignificant, even when adjusted for the significant age difference between the sexes. Furthermore, DDD selection was independent of patients' health insurance status.Conclusions: We found no significant difference in pacemaker mode selection between male and female patients. However, we did find that patients aged <65 years were more likely to have DDD pacemakers implanted compared with older patients. This age-dependent difference was primarily due to the higher prevalence of AF in the older age group versus the younger patients.Key words:pacemaker implantgender differencegender and pacemaker selection  相似文献   

20.
J. David Cairns  James McKee 《CMAJ》1964,91(20):1071-1073
A prospective study of 2000 obstetrical deliveries was undertaken to establish the incidence of single umbilical artery in the newborn and the frequency of congenital malformations reported to be associated with this disorder. Twenty cases of single umbilical artery were discovered; two proved to have an associated congenital malformation. In neither of these cases was medical management affected by the discovery of a single artery. In addition, the vascular arrangement in the cords of 31 concurrently occurring congenitally malformed babies was examined, and in no instance was a single umbilical artery found.  相似文献   

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