如何預(yù)防新生兒先天性出生缺陷

文/菲奧雷·薩爾瓦托·約里奧（Fiore S. Iorio） 譯/楊帆 賈瀟瀟

（Fiore S. Iorio，意大利），醫(yī)學(xué)博士，河北省兒童醫(yī)院外籍心臟外科專家。前意大利耶穌圣嬰兒童醫(yī)院心臟中心主任，“燕趙友誼獎”獲得者。

2015年3月3日，“世界出生缺陷日”被首次確立，其主要目的是提高全世界對先天性缺陷的認(rèn)識，促進(jìn)并整合有關(guān)預(yù)防和治療先天性畸形的行動?！笆澜绯錾毕萑铡钡脑O(shè)立是為改善生育質(zhì)量，以及提升產(chǎn)婦、新生兒、兒童和青少年的健康所采取的舉措。

并非所有出生缺陷都可以預(yù)防，但可以通過采取一些措施來幫助每一位母親擁有一個健康的孕期。

在世界各地，數(shù)以千計(jì)的出生缺陷病例都與公共衛(wèi)生相關(guān)狀況有著緊密聯(lián)系。特別是在工業(yè)化社會，以及在不斷涌現(xiàn)的新興工業(yè)化國家中，出生缺陷是嬰兒在一歲以內(nèi)發(fā)病和死亡的主要原因之一。

先天性出生缺陷的種類及治療模式

每年，全世界約有800萬嬰兒出生時(shí)患有嚴(yán)重的先天缺陷，并且其中約有300萬會在五歲之前死亡?？紤]到所有情況，先天性缺陷的發(fā)生率估計(jì)約為5%：每20個嬰兒中就會有1個患有畸形。

：例如，先天無腦畸形、左心發(fā)育不全綜合征等。此類缺陷能導(dǎo)致死產(chǎn)或新生兒和嬰兒死亡，經(jīng)產(chǎn)前診斷后一定比例的病例可能終止妊娠。

：如唇裂等。此類病例需要早期醫(yī)療干預(yù)以避免死亡或臨床狀況嚴(yán)重惡化。

如先天性髖關(guān)節(jié)脫位、隱睪。此類病例仍需醫(yī)療介入，但預(yù)期壽命良好。

致命和嚴(yán)重的先天缺陷是主要的先天性異常，而非輕微先天缺陷。

此文中非常值得注意的是海德格爾對非真理的描述。非真理包括遮蔽與迷誤。對于遮蔽，海德格爾認(rèn)為，遮蔽比顯現(xiàn)、開放更為古老，更為本源。這種遮蔽并非是存在及其真理發(fā)生之后才隨后產(chǎn)生，也并非由于人對于存在的認(rèn)識的不足與匱乏，而是因?yàn)?，存在者整體的遮蔽狀態(tài)作為根本性的非真理，比任何一種存在者和存在的敞開狀態(tài)更古老，比“讓存在”亦即存在的真理更本源。存在的真理自行遮蔽，存在在此就被遺忘了，因?yàn)槿丝偸枪虉?zhí)于“方便可達(dá)的和可控制的東西”。

導(dǎo)致出生缺陷的原因

預(yù)防出生缺陷，即在懷孕前或懷孕期間消除或減輕一些風(fēng)險(xiǎn)因素，從而使孩子出生時(shí)健康無缺陷。至少在理論上，所有原因或風(fēng)險(xiǎn)因素是已知的，最重要的是具有可更改性的，出生缺陷也可以被防治。

我們都知道，給孕期母親服用葉酸可以減少神經(jīng)管缺損的發(fā)生，我們也知道母親年齡較大是產(chǎn)兒患有21—三體綜合征（唐氏綜合征）的一個重要因素。但由于我們不能改變母親的年齡，因此對該風(fēng)險(xiǎn)因素的預(yù)防是無用的。

有效控制風(fēng)險(xiǎn)因素可以降低該缺陷或疾病的發(fā)生率。在出生前對缺陷的早期診斷可以讓父母衡量是否需要人工流產(chǎn)。但是，如果是這種情況，我們阻止的是胎兒的出生而不是缺陷本身。換句話說，我們抹去的是患者生命而不是疾病本身。因此，我們不能將其定義為一種預(yù)防，甚至這是一種錯誤的預(yù)防。

導(dǎo)致新生兒先天性缺陷主要有以下三點(diǎn)原因：

一是遺傳因素（25%），包括染色體（21—三體綜合征、18—三體綜合征、13—三體綜合征）或單基因異常（小兒手—心畸形綜合征）。造成這些缺陷的兩個主要原因是母親年齡較大（35歲以上）和近親結(jié)婚。

二是環(huán)境因素（15%）。懷孕母親不健康的飲食習(xí)慣，比如酗酒、吸煙、接觸有害物質(zhì)，如鉛、農(nóng)藥、致畸藥物、輻射、污染物；或是母親患有傳染性病原體，如水痘、巨細(xì)胞病毒、傳染性紅斑、皰疹病毒、風(fēng)疹、梅毒、弓形體病、寨卡病毒等；再或產(chǎn)婦健康紊亂，如妊娠期糖尿病、肥胖、營養(yǎng)不良等。

三是多方面因素（60%），如環(huán)境因素引發(fā)懷孕母親的健康問題。

出生缺陷的預(yù)防

先天性異常往往發(fā)病最早且完全康復(fù)的機(jī)會有限。因此，治療這類疾病的最佳醫(yī)療策略是預(yù)防。

一是戒煙戒酒。二是提倡多樣化和均衡的飲食，從孕前階段開始補(bǔ)充葉酸和維生素，避免營養(yǎng)不足、肥胖和妊娠期糖尿病。三是在母親患有慢性疾?。òd癇、糖尿病、抑郁癥、甲狀腺疾?。r(shí)，有必要與醫(yī)生一起規(guī)劃懷孕事項(xiàng)，調(diào)整相關(guān)的治療方案。四是減少接觸有害物質(zhì)，如鉛、農(nóng)藥、藥物、輻射、污染物。五是接種疫苗應(yīng)對風(fēng)疹、水痘和流感。六是注意危險(xiǎn)的傳染性病原體，如水痘、巨細(xì)胞病毒、傳染性紅斑、皰疹病毒、風(fēng)疹、梅毒、弓形體病、寨卡病毒等。七是杜絕近親結(jié)婚。八是年齡較大的父母生育的新生兒基因突變或異常的風(fēng)險(xiǎn)更大，因此建議母親的生育年齡在35歲前。

二級預(yù)防包括早期診斷和及時(shí)有效的治療，例如通過新生兒手術(shù)治療復(fù)雜的先天性心臟缺陷，如導(dǎo)管依賴性左心或右心發(fā)育不全綜合征或大動脈轉(zhuǎn)位。

最常見的先天性出生缺陷影響：骨骼、關(guān)節(jié)及肌肉（馬蹄內(nèi)翻足、先天征兆性脫位、先天性膈疝、臍疝、多指畸形、有兩個或兩個以上的指融合在一起）；腦與脊柱（先天無腦畸形、小頭畸形、腦積水、脊柱裂）；消化道（唇腭裂、食道閉鎖、肛腸直腸閉鎖）；心臟（導(dǎo)管依賴性左心或右心發(fā)育不良、大動脈轉(zhuǎn)異位、法洛四聯(lián)癥、主動脈縮窄）；泌尿道和生殖器（腎發(fā)育不全、囊性腎、膀胱外露、尿道下裂和上裂、隱睪）；唐氏綜合征。

在孕前和懷孕早期要為即將成為父母的雙方提供有針對性的建議、開展健康教育活動，為減少環(huán)境污染作出努力，更重要的是，我們需要更多的醫(yī)療監(jiān)測和持續(xù)的研究來進(jìn)行改進(jìn)，使出生缺陷的預(yù)防變得更加有效。

On March 3, 2015, for the first time, “World Birth Defect Day” (WBDD) was celebrated with the main objective to raise awareness all around the world about birth defects and to promote and integrate actions for the prevention and treatment of congenital malformations and, in general, for the improvement of reproductive, maternal, neonatal, childhood and adolescent health.

Not all birth defects can be prevented, but you can take steps to help the mother have a healthy pregnancy.

There are thousands of birth defects representing a relevant condition in public health anywhere in the world. In industrialized societies, and increasingly also in emerging societies, they are one of the leading causes of infant morbidity and mortality within the first year of life.

Every year, about eight million babies worldwide are born with a serious birth defect, and about three millions of them will die before their fifth birthday. Considering all cases, the frequency of congenital defects can be estimated at around 5%: one in 20 babies born has a malformation.

when they may cause stillbirth or neonatal and infant death, or when pregnancies may be terminated in a relevant proportion of cases after prenatal diagnosis (anencephaly, hypoplastic left heart syndrome).

when they need early medical intervention to avoid death or major impairment of clinical conditions (cleft lip).

when they still need medical intervention, but life expectancy is good (congenital dislocation of the hip, cryptorchidism).

Lethal and severe defects represent significant congenital anomalies instead of minor ones.

Prevention of birth defects means elimination or mitigation of the causes or risk factors before or during pregnancy, thus allowing the child to be born healthy and without defects. All birth defects whose causes or risk factors are known and, most of all, modifiable can also be prevented, at least in theory.

For example, the administration of folic acid reduces neural tube defects to the mother, and we also know that the older age of the mother is a risk factor for the birth of a neonate with trisomy 21 (Down syndrome). But since we cannot modify that mother's age, this risk factor is useless for prevention.

Effective control of a cause or risk factor of a birth defect will result in a percentage reduction of the incidence of that defector disease. The early diagnosis of the defect in prenatal age allows the parents to evaluate whether to terminate the pregnancy. But, if this is the case, we prevent the birth of the fetus, not the defect itself. In other words, we eliminate the patient, not the disease. We cannot define this as prevention but false prevention.

The causes of congenital birth defects are:

including chromosomal (trisomy 21 Down syndrome, trisomy 18 Edwards syndrome, trisomy 13 Patau syndrome) or single gene anomaly (Holt-Oram syndrome). The two major risk factors for these defects are the older age of the mother (＞35 years) and consanguineous marriages.

due to unhealthy habits of the mother like alcohol abuse and smoking; exposure to harmful substances such as lead, pesticides, teratogenic drugs, radiation, pollutants; infectious agents (chickenpox, cytomegalovirus, infectious erythema, herpes virus, rubella, syphilis, toxoplasmosis, Zika virus, etc.); maternal health disorders (gestational diabetes, obesity, nutritional deficiencies).

: when environmental risk factors trigger the mother's predisposition.

Congenital abnormalities have the earliest onset and a limited chance for complete recovery; therefore, the best medical strategy to approach these types of diseases is prevention.

Primary prevention of congenital defects is a priority for the consequences in the social and health field as a cause of mortality and infant morbidity. Many birth defects can be avoided by taking preventive actions before and during pregnancy. It is therefore strategic to offer any woman of childbearing age extensive counseling to promote healthy lifestyles, with particular reference to the following aspects.

elimination of alcohol and smoking., promotion of a varied and balanced diet, also through folic acid and vitamins supplementation from the preconceptional phase to avoid nutritional deficiencies, obesity, gestational diabetes.in the presence of chronic diseases of the mother (epilepsy, diabetes, depression, thyroid disease), it is necessary to plan the pregnancy with the doctors to manage the related treatment.reduction of exposure to harmful substances such as lead, pesticides, drugs, radiation, pollutants.favor a vaccination strategy against rubella, chickenpox and flu.beware of dangerous infectious agents (chickenpox, cytomegalovirus, infectious erythema, herpes virus, rubella, syphilis, toxoplasmosis, Zika virus, etc.).avoid marriages between relatives for the risk of inbreeding.try to favor the mother's age ＜35 years as genetic factors such as gene mutations or abnormalities may occur more frequently in older parents.

Secondary prevention includes early diagnosis and prompts effective treatment, e.g., neonatal surgical treatment of complex congenital heart defects such as ductus-dependent hypoplastic left or right heart syndrome or transposition of the great arteries.

The most common congenital birth defects affect:s (clubfoot, congenital dislocation of the hint, congenital diaphragmatic hernia, omphalocele, polydactyly, syndactyly);(anencephaly, microcephaly, hydrocephaly, spina bifida);(cleft lip/palate, esophageal atresia, anorectal atresia);(ductusdependent hypoplastic left or right heart, transposition of the great arteries, tetralogy of Fallot, coarctation of the aorta);(renal agenesis, cystic kidney, bladder exstrophy, hypospadias, epispadias, undescended testis);

Tailored advice to future parents during preconceptional and early pregnancy consultations, health education campaigns for prospective parents, international efforts to reduce environmental pollution. But, most of all, medical surveillance and continuous research are needed to improve and make birth defects more and more effective in the future.