Assessment of Awareness and Understanding of Hemolytic Disease of the Fetus and Newborn in the Beninese Population

Background: Hemolytic Disease of the Fetus and Newborn (HDFN) arises from blood group incompatibility, especially the RhD antigen. In Benin, systematic ABO RhD blood grouping is poorly understood by many midwives and nurses. Nearly one in ten women risk having children with HDFN. This study aimed to determine the level of knowledge of the Beninese population on HDFN. Methods: Data were collected from June 2023 to March 2024. Participants completed a Kobotoolbox questionnaire on WhatsApp, with in-person assistance for illiterate participants. The study involved 521 participants from across Benin. Data were analyzed using SigmaPlot version 14.0. Results: Among the 521 participants, 298 were women (57.20%) aged 18 to 77 years. The majority (40.69%) were aged 26 - 35. Over a third (35.51%) did not know their RhD blood group. Most (59.12%) were unaware of the risks for RhD discordant couples. Among those with a partner, 25.16% were in at-risk couples for HDFN, and over half (59.12%) were unaware of this risk. There was no significant association between being in a high-risk union and knowledge of the risk or education level. Conclusion: Only 40.88% of the Beninese population are aware of HDFN, indicating a low level of knowledge.

Epidemiological, Clinical Progress Aspects of Congenital Heart Disease with Neonatal Revelation at the Mother-Child Hospital of Bingerville (HME) Concerning 98 Cases from January 2021 to December 2022 (Côte d’Ivoire)

Introduction The distribution of congenital heart disease (CHD) in sub-Saharan Africa is highly imprecise and varies from one region to another due to the inequality of diagnostic facilities. The aim of this study was to determine the in-hospital prevalence of congenital heart disease in children at the Mother-Child hospital of Bingerville (HME) by specifying the diagnostic, therapeutic and evolutionary aspects. Materials and methods We conducted a retrospective, descriptive, cross-sectional study at HME of Bingerville from January 2021 to December 2022. All newborns with congenital heart disease confirmed by echocardiography were included in the study. Results Of 656 admissions to the neonatology department over the study period, congenital heart disease accounted for 14.9% (98/656) of cases. In our series, 76.7% were diagnosed before the 1st week of life, with a mean chronological age of 5.18 days and extremes of 0 and 46 days. There were as many male patients (50%) as female (50%), i.e. a sex ratio of 1. These newborns were premature in 60.2% of cases, with a mean and median gestational age of 34 weeks’ amenorrhea. Most were left-right shunts (90.8%). Persistent ductus arteriosus (PDA) (48.9%) predominated, followed by atrial septal defect (38.7%), ventricular septal defect (13.3%), common trunk artery (CTA) (3.1%) and open septal pulmonary atresia (OSPA) (1%) as the primary cyanogenic heart disease. Pulmonary arterial hypertension (PAH) (50%) was primary in 38.8% and secondary (61.2%). The mortality rate was 30.6%, and all CTA patients died (100%), with a significant statistical relationship (p = 0.027). Progression under treatment was marked by clinical stabilization (68/98) in 69.4% of cases. Conclusion: Congenital heart disease is relatively common at the Bingerville HME. Access to echocardiography should be facilitated in neonatology departments for rapid diagnosis and optimal management of congenital heart disease in newborns.

Rh-incompatible hemolytic disease of the newborn in Hefei

BACKGROUND Anti-D antibody is not the common cause of Rh-isoimmunization in Chinese neonatal jaundice.Recent change in national population policy has followed by an increase in Rh-isoimmunization related hemolytic disease of the newborn(HDN).Unfortunately,regional status of Rh-HDN is unavailable.We hypothesize that Rh-HDN in our region is most commonly due to anti-E antibody.AIM To investigate the prevalence of hemolytic disease of the newborn due to Rhisoimmunization in Hefei City.METHODS Retrospective review of data obtained from Children’s Hospital of Anhui and Hefei Blood Center between January 2017 and June 2019.Status of minor blood group antibody was studied in the corresponding mothers.RESULTS Totally 4138 newborns with HDN admitted during the study period and 116(2.8%)received blood exchange transfusion(BET).Eighteen newborns(0.43%)with proven Rh-incompatible HDN were identified.All were not the first-born baby.Thirteen mothers were RhD(+)(72%)and five were RhD(-).The distribution of Rh-related antibodies in mothers was ten anti-E(55%),five anti-D(27%),and for one anti-C,anti-c,and anti-E/c(6%)each.Thirteen(72.2%)were qualified for BET,relative risk for BET was 28.9 as compared to other types of HDN,but only 10 received due to parenteral refusal.All(100%)RhD related HDN received BET which is not significantly different from RhE related HDN(81.8%).CONCLUSION As expected,all Rh-incompatible HDN newborns were not the first-born.Contrary to the Caucasian population,anti-D induced HDN is not the most common etiology.In our region,anti-E(11/18,61%)is the most common cause of Rh-HDN.

A CASE OF HEMOLYTIC DISEASE OF THE NEWBORN CAUSED BY ANTI-HRO AND ANTI-E

A Chinese woman of blood group B,D-and her husband of blood group AB,CCDeewere examined.The woman had not been transfused before.Their first two babiesdied.Anti-Hro and anti-e were found in the mother’s serum.During her third pregnancy,the titer of antibodies went up quickly,approximately one titer per month.After 36 weeksof pregnancy,the baby was delivered by Caesarean section.The cord blood Hb was 88g/L,his red blood cell count 2.7×1012/L,and total biIirubin 114.6 mol/L.The baby was ofblood group AB,and CDe-D-genotype.Exchangetransfusion was begun 2.5 hours afterbirth.O,ccDEE washed red cells together with group AB plasma were used.Two dayslater,7Oml washed O,ccDEE concentrated red cells were administered.The baby is aliveand in good health.

Oxidative stress and free radicals related diseases of the newborn

Free radicals (FRs) generation is an unavoidable consequence of the life in an oxygen-rich atmosphere. FRs can be considered a double-edged sword. Beneficial effects of FRs occur at moderate concentrations and involve physiological roles in cellular responses to noxia, as in defense against infectious agents, in the function of a number of cellular signaling pathways and the induction of a mitogenic response. The over-production of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS), a deleterious process and important mediator of damage to cell structures and tissues. It occurs at birth in all newborns as a consequence of the hyperoxic challenge after the transition from the hypoxic intrauterine environment to extrauterine life. During the perinatal period, OS can be magnified by others predisposing conditions such as hyperoxia, hypoxia, ischemia, hypoxia-reperfusion, inflammation and high levels of non-protein bound iron. Epidemiological studies linked OS occurring during fetal stages and early infancy with adverse health outcomes later in life, indicating that OS is an early event in the etiology of these chronic diseases. Newborns, especially if preterm, are particularly susceptible to OS and damage due to the increased generation of FRs, the lack of adequate antioxidant protection, and the inability to induce antioxidant defenses during the hyperoxic challenge at birth. This impairment of the oxidative balance has been thought to be the common factor of pathologies grouped together as “free radical disease in the neonate” that include retinopathy of prematurity (which may lead to blindness in severe cases), bronchopulmonary dysplasia (a particularly debilitating pulmonary lesion of the preterm infant), periventricular leukomalacia (an important cause of severe neurodisability) and necrotizing enterocolitis. In this review we discuss in detail these perinatal diseases. Particularly, we analyze the current knowledge about the role of OS in their pathogenesis.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Prevalence and outcome of acute kidney injury,as defined by the new Kidney Disease Improving Global Outcomes guideline,in very low birth weight infants

AIMTo evaluate the prevalence, risk factors and outcome of acute kidney injury （AKI） in very low birth weight （VLBW） infants. METHODSIn this retrospective study of VLBW infants, we analyzed the prevalence of AKI, as defined by changes in serum creatinine and urine output, associated risk factors and outcomes.RESULTSA total of 293 VLBW infants （mean gestational age 28.7 wk） were included, of whom 109 weighed less than 1000 g at birth. The overall prevalence of AKI was 11.6% （22% in infants with a birth weight under 1000 g and 5.4% those heavier）. A total of 19 （55%） affected infants died, with a mortality rate of 58% in infant less than 1000 g and 50% in those heavier. After adjusting for confounding variables, only necrotizing enterocolitis （NEC） remained associated with AKI, with odds ratio of 4.9 （95%CI： 1.9-18.6）. Blood pressure and glomerular filtration rate （GFR） were not different between affected infants and the others upon discharge from hospital. A normal GFR was documented in all affected infants at one year of age.CONCLUSION Using Kidney Disease Improving Global Outcomes defnition of AKI, it occurred in over 10% of VLBW infants, more commonly in infants with lower birth weight. NEC was an independent associated risk factor. Renal function, as defined by GFR, was normal in all surviving affected infants 10 to 12 mo later.

Efficacy of Whole Blood Reconstituted (WBR) in Exchange Transfusion (ET) in Hemolytic Disease of New Born (HDN) —A Study of 110 Cases

Aim: This study was aimed to review and establish the practice of exchange transfusion (ET) with whole blood reconstituted (WBR) in hemolytic disease of newborn (HDN). Objectives: To observe fall in indirect serum bilirubin, correction of anemia and comparison with related studies. Background: Hemolytic disease of the Newborn is characterized by presence of IgG antibodies in maternal circulation, which causes hemolysis in the fetus by crossing the placenta and sensitizing red cells for destruction by macrophages in the fetal spleen with consequent hyperbilirubinemia. Exchange transfusion with or without phototherapy is the method of choice for treating the newborn with on going hemolysis Methods/Materials: Sample size consisted of 110 neonates in whom 119 exchange transfusions were carried out with WBR. WBR was prepared by suspending O Rhesus-D (RhD) positive/negative cells (compatible with neonate’s/ mother’s serum) in AB plasma. Double volume exchange transfusion(s) were carried out through umbilical vein by push-pull technique. Results: Out of 110 cases, 61 (55.5%) were of RhD HDN whereas ABO and other group HDN cases were 30 (27.3%) and 19 (17.3%) respectively. An average post-ET fall in indirect serum bilirubin by 54.6% and correction of anemia by3.7 gm/dl were reported in the study. Conclusion: An average post-ET fall in indirect serum bilirubin and correction of anemia was found to be more significant when compared to other studies. Hence we recommend exchange transfusion in HDN with WBR to obtain reasonable fall in indirect serum bilirubin and high average rate of correction of anemia.

抗-M致胎儿新生儿溶血病实验室检测及预防策略分析

目的分析血清学检测结果在抗-M致胎儿新生儿溶血病(HDFN)诊断和治疗中的应用,探讨HDFN预防策略。方法对2017年1月—2023年12月本实验室确诊的12例抗-M引起的HDFN血清学检测结果进行回顾性分析,包括母亲和患儿的血型鉴定,血清总胆红素、血红蛋白、抗体效价检测,新生儿溶血3项实验。收集患儿和母亲的临床资料,包括妊娠史、输血史、产前抗体检测、宫内输血史、分娩孕周,并随访患儿预后。结果12例抗-M引起的HDFN中,患儿母亲均为RhD+NN表型,患儿均为RhD+MN表型,母子MN血型均不相容。在ABO血型系统中,母子ABO血型不相容占41.7%(5/12)。患儿母亲皆无输血史,在4℃检测效价中位数32,37℃效价中位数4。3例患儿母亲有多次宫内输血史,发生率为25%(3/12)。1例为首胎妊娠异常,占比8.3%(1/12),7例为异常妊娠流产,不良孕产史发生率58.3%(7/12)。6例患儿母亲早产,占比50%(6/12)。3例患儿母亲定期产检,并鉴定抗体特异性,占比25%(3/12)。12例患儿游离抗体在4℃检测效价中位数6,37℃效价中位数2。2例患儿抗-M在37℃检测无反应,阴性率16.7%(2/12)。患儿直抗阳性率8.3%(1/12),放散阳性率16.7%(2/12)。血红蛋白最低值中位数75 g/L,12例患儿均接受了输血治疗。总胆红素峰值中位数157.5μmol/L,均未达到换血阈值。患儿迟发性贫血率16.7%(2/12),患儿出生后死亡率8.3%(1/12),11例患儿预后无生长和神经发育迟缓情况。结论抗-M能引起严重的HDFN,也可发生于第1胎,抗体效价强度与疾病的严重程度不相关,容易引起迟发性贫血,应根据抗-M血清学特征和临床症状定期监测,及时干预治疗。

血清抗体、血红蛋白、胆红素、心肌酶及肝酶联合对新生儿Rh溶血病的诊断效果

目的研究血清抗体、血红蛋白、胆红素、心肌酶及肝酶联合对新生儿Rh溶血病的诊断效果。方法选择2021年7月至2022年11月于赣州市人民医院分娩的53例新生儿Rh溶血病患儿,按照疾病严重程度分为重症组20例和轻症组33例,检测并比较血清抗体、血红蛋白、胆红素、心肌酶及肝酶水平,分析其诊断价值。结果重症组血红蛋白低于轻症组,胆红素、肌酸激酶、丙氨酸氨基转移酶高于对照组(P<0.05);两组血清抗体比较,差异无统计学意义(P>0.05);经logistic多因素分析结果显示,血清血红蛋白(β=-0.136,OR=0.873,95%CI:0.814~0.936)是新生儿Rh溶血病的保护因素(P<0.05);胆红素(β=0.031,OR=1.032,95%CI:1.012~1.052)、肌酸激酶(β=0.093,OR=1.098,95%CI:1.039~1.160)及丙氨酸氨基转移酶(β=0.120,OR=1.128,95%CI:1.042~1.221)是新生儿Rh溶血病的危险因素(P<0.05);绘制ROC曲线图,结果显示,血清血红蛋白、胆红素、心肌酶及肝酶联合检测在新生儿Rh溶血病诊断中的AUC分别为0.938、0.817、0.815、0.929、0.977,均有一定诊断价值。结论血清血红蛋白、胆红素、心肌酶及肝酶联合检测在新生儿Rh溶血病诊断中有一定应用价值。

单核细胞单层试验在预测IgG抗-M相关胎儿新生儿溶血病中的应用

目的探讨单核细胞单层实验(monocyte monolayer assay,MMA)是否能够用于IgG抗-M相关胎儿新生儿溶血病(hemolytic disease of fetus and newborn,HDFN)的预测。方法选取8例含有IgG抗-M的孕妇并采集血浆标本,其中有胎儿水肿等严重临床症状及无明显临床症状的各4例;8份血浆用二硫苏糖醇(dithiothreitol,DTT)灭活,与M抗原阳性红细胞孵育致敏后,将致敏红细胞与单核细胞混合进行吞噬试验,同时设立阳性及阴性对照,并计算吞噬率;采用t检验对2组吞噬率进行比较。结果4例发生严重抗-M相关HDFN的孕妇的MMA吞噬率分别为15.37%、13.05%、9.17%和24.50%,均值为15.52%;检出IgG抗-M但未发生HDFN的孕妇,其MMA吞噬率分别为8.74%、11.07%、5.12%和6.23%,均值为7.79%,2组吞噬率无差异(P>0.05)。2组吞噬率分别与阴性对照比较均无差异(P>0.05),但均明显低于阳性对照(P<0.05)。结论IgG抗-M介导单核细胞吞噬的能力较低,提示抗-M导致胎儿水肿的机制可能并非红细胞被吞噬破坏而发生的溶血,因此体外单核细胞单层实验可能不适用于IgG抗-M相关HDFN的预测。对于检出IgG抗-M的孕妇,现仍需通过定期监测胎儿大脑中动脉血流,来判断胎儿宫内贫血情况。

罕见抗-Di^(b)致严重胎儿新生儿溶血病的实验室检测与相关研究

目的对1例高频抗体导致的胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)进行检测、鉴定及配血。方法对患儿进行新生儿溶血试验,对母亲进行血清学意外抗体鉴定,并对母亲红细胞进行常见高频抗原鉴定;对检出抗体进行IgG分型检测,并用流式细胞术进行单核细胞体外吞噬致敏红细胞试验,以检测抗体相关的吞噬率;对患儿母亲、父亲及舅舅进行相关红细胞血型基因测序;利用稀释的母亲血浆和抗人球卡法,在献血者中进行大规模相合血液的筛选。结果产妇鉴定为Di(b-)稀有血型,产生了抗-Di b(效价512)并导致了严重的HDFN;抗-Di b亚型分型为IgG1和IgG2型,单核细胞体外吞噬效率为88.83%(74.7/84.09);产妇亲属中没有相合献血者,后续从5520名献血者中筛选到2例Di(b-)相合血液,患儿接收输血治疗后康复出院。后续在51334名献血者中筛查到17名Di(b-)献血者,该数据表明Di(b-)在广州地区献血者中的分布频率约为三千分之一(0.033%,17/51334)。结论综合利用血型血清学及分子生物学方法诊断了抗-Di b所致的严重HDFN,建立了1种有效大规模筛查Di(b-)稀有血型的方法并找到相合血液,为建立Di(b-)稀有血型库奠定了基础。

新凝血标志物在新生儿弥漫性血管内凝血诊断及预后评估中的价值

目的探讨新凝血标志物血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2抗纤溶酶复合物(PIC)和组织型纤溶酶原激活剂-纤溶酶原激活剂抑制剂-1复合物(t-PAIC)在新生儿弥漫性血管内凝血(DIC)诊断及预后评估中的价值。方法纳入87例DIC患儿(观察组),根据其出院时的转归情况分为存活组(66例)和死亡组(21例),另外以同期出生的50例健康新生儿作为对照组。收集新生儿的临床资料,采用Logistic回归分析新生儿发生DIC的危险因素。分析不同组别TM、TAT、PIC和t-PAIC水平差异。采用受试者工作特征(ROC)曲线分析TM、TAT、PIC和t-PAIC在新生儿DIC诊断和预后评估中的价值。结果观察组低Apgar评分、出生窒息、IVH、脓毒症和PIH的发生率高于对照组(P<0.05)。多因素Logistic回归分析显示,低Apgar评分、出生窒息、脓毒症和PIH是新生儿发生DIC的独立危险因素。观察组TM、TAT、PIC和t-PAIC水平均高于对照组(P<0.05)。ROC曲线显示,TM、TAT、PIC和t-PAIC联合诊断新生儿DIC的价值优于单独诊断。死亡组TM、TAT水平高于存活组(P<0.05),2组PIC、t-PAIC差异无统计学意义;多因素Logistic回归分析显示,TAT水平升高是影响新生儿DIC预后的独立危险因素。ROC曲线显示,当TAT为21.72μg/L时,其预测新生儿DIC预后的曲线下面积为0.772(95%CI:0.666~0.878),敏感度和特异度分别为76.2%和71.2%。结论TM、TAT、PIC和t-PAIC联合应用对新生儿DIC诊断和预后评估具有重要的临床价值。

微柱凝胶技术与凝聚胺技术在ABO新生儿溶血病输血前检测中应用对比

目的对比分析微柱凝胶技术与凝聚胺技术在ABO新生儿溶血病输血前检测中的应用。方法将郑州市第一人民医院2020年1月至2023年5月ABO新生儿溶血病患儿(88例)作为研究对象,依据区间随机法将其分为对照组、研究组,各纳入44例,对照组行输血治疗前开展凝聚胺技术检验血型配血,研究组输血治疗前开展微柱凝胶技术检验血型配血。比较两组检验符合率、一次性交叉配血成功率。结果研究组正定型、反定型符合率(100.00%、100.00%)均高于对照组(86.36%、86.36%),两组差异有统计学意义(P<0.05);研究组交叉配血成功率(100.00%)高于对照组(86.36%),两组差异有统计学意义(P<0.05)。结论对比凝聚胺技术,微柱凝胶技术在ABO新生儿溶血病输血前检测中的应用价值更高,有利于提升输血安全,值得应用。

RhD阴性孕产妇与HDFN发生的相关性及影响因素分析

目的 通过对RhD阴性孕产妇腹中胎儿和分娩的新生儿发生胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)的相关指标对比分析,为预防和治疗HDFN提供参考和指导。方法 收集我院2018年1月—2022年12月分娩的RhD阴性孕产妇737名,比较新生儿是否发生RhD血型不合、ABO血型不合导致的HDFN及其影响因素,发生RhD-HDFN和发生ABO-HDFN的相关影响因素。分析发生RhD-HDFN和发生ABO-HDFN患儿的实验室指标差异;分析IgG抗-D效价≤16和≥32的孕产妇分娩的新生儿发生RhD-HDFN的实验室指标差异。结果 737名RhD阴性孕产妇中,发生RhD-HDFN的母婴ABO血型相同或相容者比率88.89%(40/45)显著高于母婴ABO血型不相容者11.11%(5/45)。母体二次妊娠及以上发生RhD-HDFN比率93.33%(42/45)显著高于ABO-HDFN 60.66%(37/61)者。母体IgG抗-D效价≥32者分娩的新生儿血红蛋白(hemoglobin,Hb)最低值低于母体IgG抗-D效价≤16者(χ^(2)=5.61,P<0.05),母体IgG抗-D效价≥32者分娩的新生儿血清总胆红素(total bilirubin,TBil)峰值高于IgG抗-D效价≤16者(χ^(2)=4.471,P<0.05)。结论 RhD阴性孕产妇中,母婴ABO血型相同或相容及孕产次≥2者,相应新生儿更易发生RhD-HDFN,母体IgG抗-D效价≥32者发生新生儿溶血的严重程度显著高于抗-D效价≤16者。

优化质量控制体系与评价指标对新生儿遗传代谢病筛查效率的影响分析

目的 分析优化质量控制体系与评价指标对新生儿遗传代谢病筛查(简称新筛)效率的影响。方法 采用管理质量、血片质量、诊治质量3个维度的13个评价指标,分析浙江省《质量控制监测与评价指标》(简称《指标》)建立前的2013年,建立后的2015年、修订后的2020年和2023年新筛工作质量变化,了解考核与管理指标对新筛工作的实际影响。结果 2013、2015、2020和2023年之间浙江省新筛率和召回率经卡方检验差异有统计学意义(P<0.05),但经线性回归检验后差异无统计学意义(P>0.05)。不同年份之间浙江省新生儿遗传代谢病的血片不合格率、血片不合格数未补采率、血片迟递率和血片缺错项率经卡方检验差异均有统计学意义(P<0.05),2023年上述指标均达到最低值;并通过线性回归检验后显示血片不合格率、血片不合格数未补采率和血片缺错项率有下降趋势(P<0.05)。不同年份之间先天性甲状腺功能减低症(CH)和苯丙酮尿症(PKU/BH4D)生后2、3和4周的诊断率和治疗率经卡方检验差异均有统计学意义(P<0.05),经线性回归进行趋势检验后CH生后2、4周诊断率和治疗率及PKU/BH4D生后3周诊断率和治疗率有上升趋势(P<0.05)。结论 通过建立和优化可量化的《指标》能有效评价和提升浙江省新筛的工作效率,从而进一步加强对于出生缺陷的防治能力。

先天性肌张力低下新生儿32例的遗传学分析

目的探讨先天性肌张力低下新生儿的致病性基因突变特点、临床特征以及预后情况,为临床医生早期识别疾病及选择合理的干预措施提供参考。方法回顾性分析安徽省儿童医院新生儿重症监护病房2019年6月至2022年6月收治的以肌张力低下为主要临床表现的新生儿的临床特征及基因检测结果。结果研究共纳入32例患儿,均有肌张力低下表现,其中中枢性肌张力低下20例(62.5%),周围性肌张力低下12例(37.5%)。经基因测序后共发现21种疾病,26种基因型,其中新发突变来源的基因型有14种(RIT1、KRAS、BRAF、PHOX2B、HNRNPK、RAI1、KMT2D、OTC、AHDC1、DMD、COL12A1、MT-ATP6、FLNC、RYR1)。对所有患儿进行随访,死亡20例。结论先天性肌张力低下病因复杂,基因测序可以提高早期诊断率,扩宽先天性肌张力低下的表型-基因型谱,替代部分侵入性检查,同时指导临床管理以及家庭的遗传咨询。