如何預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），醫學博士，河北省兒童醫院外籍心臟外科專家。前意大利耶穌圣嬰兒童醫院心臟中心主任，“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識，促進并整合有關預防和治療先天性畸形的行動?！笆澜绯錾毕萑铡钡脑O立是為改善生育質量，以及提升產婦、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，數以千計的出生缺陷病例都與公共衛生相關狀況有著緊密聯系。特別是在工業化社會，以及在不斷涌現的新興工業化國家中，出生缺陷是嬰兒在一歲以內發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800萬嬰兒出生時患有嚴重的先天缺陷，并且其中約有300萬會在五歲之前死亡。考慮到所有情況，先天性缺陷的發生率估計約為5%：每20個嬰兒中就會有1個患有畸形。

：例如，先天無腦畸形、左心發育不全綜合征等。此類缺陷能導致死產或新生兒和嬰兒死亡，經產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療干預以避免死亡或臨床狀況嚴重惡化。

如先天性髖關節脫位、隱睪。此類病例仍需醫療介入，但預期壽命良好。

致命和嚴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，海德格爾認為，遮蔽比顯現、開放更為古老，更為本源。這種遮蔽并非是存在及其真理發生之后才隨后產生，也并非由于人對于存在的認識的不足與匱乏，而是因為，存在者整體的遮蔽狀態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，因為人總是固執于“方便可達的和可控制的東西”。

導致出生缺陷的原因

預防出生缺陷，即在懷孕前或懷孕期間消除或減輕一些風險因素，從而使孩子出生時健康無缺陷。至少在理論上，所有原因或風險因素是已知的，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管缺損的發生，我們也知道母親年齡較大是產兒患有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，因此對該風險因素的預防是無用的。

有效控制風險因素可以降低該缺陷或疾病的發生率。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。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防，甚至這是一種錯誤的預防。

導致新生兒先天性缺陷主要有以下三點原因：

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）和近親結婚。

二是環境因素（15%）。懷孕母親不健康的飲食習慣，比如酗酒、吸煙、接觸有害物質，如鉛、農藥、致畸藥物、輻射、污染物；或是母親患有傳染性病原體，如水痘、巨細胞病毒、傳染性紅斑、皰疹病毒、風疹、梅毒、弓形體病、寨卡病毒等；再或產婦健康紊亂，如妊娠期糖尿病、肥胖、營養不良等。

三是多方面因素（60%），如環境因素引發懷孕母親的健康問題。

出生缺陷的預防

先天性異常往往發病最早且完全康復的機會有限。因此，治療這類疾病的最佳醫療策略是預防。

一是戒煙戒酒。二是提倡多樣化和均衡的飲食，從孕前階段開始補充葉酸和維生素，避免營養不足、肥胖和妊娠期糖尿病。三是在母親患有慢性疾病（癲癇、糖尿病、抑郁癥、甲狀腺疾病）時，有必要與醫生一起規劃懷孕事項，調整相關的治療方案。四是減少接觸有害物質，如鉛、農藥、藥物、輻射、污染物。五是接種疫苗應對風疹、水痘和流感。六是注意危險的傳染性病原體，如水痘、巨細胞病毒、傳染性紅斑、皰疹病毒、風疹、梅毒、弓形體病、寨卡病毒等。七是杜絕近親結婚。八是年齡較大的父母生育的新生兒基因突變或異常的風險更大，因此建議母親的生育年齡在35歲前。

二級預防包括早期診斷和及時有效的治療，例如通過新生兒手術治療復雜的先天性心臟缺陷，如導管依賴性左心或右心發育不全綜合征或大動脈轉位。

最常見的先天性出生缺陷影響：骨骼、關節及肌肉（馬蹄內翻足、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（導管依賴性左心或右心發育不良、大動脈轉異位、法洛四聯癥、主動脈縮窄）；泌尿道和生殖器（腎發育不全、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，為減少環境污染作出努力，更重要的是，我們需要更多的醫療監測和持續的研究來進行改進，使出生缺陷的預防變得更加有效。

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.