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作者：Pauline Anderson  
出處：WebMD醫學新聞

　　December 17, 2009 — 根據一篇新研究，一種測量新生兒神經和行為問題的量表，可預測孩童期的發育遲緩。
　　
　　根據比較生產前曝露於藥物之嬰兒與對照組嬰兒之結果的研究，這個量表－Neonatal Intensive Care Unit Network Neurobehavioral Scale(NNNS)－在預測孩童到學齡前發育問題上，優於妊娠年齡與社會經濟狀態(socioeconomic status[SES])。
　　
　　NNNS包括：測量追蹤有生命和無生命之聽覺和視覺刺激的能力、張力亢進的反應、昏睡、激動與壓力程度，需時20分鐘完成，可以由任何經訓練的醫療人員提供。
　　
　　及早發現發育問題是重要的，研究顯示，孩童如果越早接受幫助，越可能獲益。
　　
　　研究的第一作者、羅德島布朗大學布朗孩童風險研究中心主任Barry表示，雖然還不能提議普遍進行NNNS篩檢，但在未來將是可行的。
　　
　　Lester博士向Medscape Psychiatry表示，如果，第1、我們知道它對其他人也有用，第2、我們完成治療研究且結果顯示我們可以有效介入與預防不佳結果，那麼，就值得進行普遍篩檢。
　　
　　這項研究線上發表於12月7日的小兒科(Pediatrics)期刊。
　　
　　【藥物曝露】
　　該研究的研究對象來自「Maternal Lifestyle Study」這個多中心縱向研究，這些嬰兒在產前即曝露於藥物且早產。目前的這次分析包括在產前曝露於古柯鹼的658名嬰兒，這些孩童和730名未曾曝露於古柯鹼的對照組比較，兩組的妊娠年齡、性別、種族等相仿。
　　
　　除了確認嬰兒是否有曝露於古柯鹼、鴉片類藥物、香菸、酒精、和/或大麻之外，也瞭解這些曝露的程度，研究者於44週時蒐集有關嬰兒出生體重、身長、頭圍、顱內超音波等資料。
　　
　　原本納入的嬰兒中有90%(1248/1388)在1個月回診時進行NNNS。根據NNNS分數，嬰兒們被分成5個風險類別，類別5為分數最差者。
　　
　　相較於其他嬰兒，類別5的72個嬰兒(總樣本的5.8%)有注意力不佳且相當激動、興奮、張力亢進、相當有壓力。這些嬰兒傾向曾經有產前酒精與藥物曝露、早產或低出生體重。它們有半數以上體重小於2500g。
　　
　　接下來的3年，研究者進行嬰兒發育檢測，包括「Bayle心智發育指數」和「精神運動發展評估」。第3年訪視時，母親們完成「兒童行為檢核表(Child Behavioral Checklist[CBCL])」。第4年訪視時，研究者評估就學意願，4.5年時，使用「Wechsler學前兒童和小學生智力量表」測量智商。
　　
　　研究發現，類別5的嬰兒大約40%有臨床明顯的行為問題與就學意願問題，35%智商偏低，此外，令人擔心的是，42%的CBCL檢測的整體行為分數不正常。
　　
　　約有22%的嬰兒屬於類別4、次糟的一組。這些嬰兒的身心狀態很極端、最多非最佳的反應、動作品質不佳、許多壓力徵兆。
　　
　　整併類別4和5這兩組時，研究者發現其他發育警訊。Lester博士表示，如果加入類別4，各種不同結果的孩子增加了一些，但是，是否只用類別5或者加入類別4，需依照這在不同族群中的影響。
　　
　　只有納入曾經曝露於藥物且早產的嬰兒是目前的研究限制。Lester博士等人在美國和其他國家的不同族群，使用NNNS進行其他研究。
　　
　　【更好的預測因子】
　　控制妊娠年齡和SES之後 — 這是兩個也可以預測發育結果不佳的變項 — NNNS依舊可有效預測類別5嬰兒在1個月時的異常超音波(勝算比 [OR]為2.37；相較於其他類別)、慢性神經痛異常(OR為2.35)、外化行為問題(OR為2.05)、內化行為問題(OR為 2.72)與整體行為問題(OR為2.37)。
　　
　　Lester博士表示，即使是以出生體重和SES之預測與NNNS一樣，你無計可施，但是我們可以。
　　
　　你無法改變嬰兒的出生體重，你也無法改變嬰兒的貧困程度，但是嬰兒的行為是你可以加以嘗試並有所改善的。
　　
　　發現發育問題且及早開始介入措施，可以有適當的長期利益。Lester博士表示，如果我們確認類別5的小孩在4歲時很可能面臨麻煩，或許我們可以根據這些資料發展一種介入方式，看這些介入方式是否可以減少或預防問題。
　　
　　【不正確的標記】
　　如同任何量表一樣，NNNS並不完美；不可避免的會有一些嬰兒被不正確的標記為有發育問題，也有許多在嬰兒時期看似有問題的孩童繼續正常發育。
　　
　　Lester博士指出，對嬰兒做出錯誤標示會造成自我應驗預言，父母們無意間對他們的嬰兒有不同的對待，可能視他們如脆弱般、未能提供適當的刺激、他們可能相當焦慮，所以可能反而造成許多極力避免的問題。
　　
　　不過，他指出，NNNS是種非侵犯性且有利的早期介入，他也認為，父母親終究須評估其嬰兒的NNNS結果，然後他們自己決定如何因應這些資訊。他將這比喻為乳癌基因BRCA-1和BRCA-2，如果你有一個讓你容易發生乳癌的基因，你應被告知該資訊並且決定你要如何處置。
　　
　　【印象深刻且重要】
　　華盛頓特區美國兒童與青少年精神科學院、學齡前嬰兒委員會主席、華盛頓大學醫學院精神科教授Joan Luby醫師發表對此研究的評論時表示，這個發現令人印象深刻且重要。
　　
　　Luby醫師表示，還需一段長時間，這個結果才可以彌補新生兒將面對的困難問題的「黑洞」，需要完成更多研究，不過，本研究提供了關鍵部份。
　　
　　Luby醫師指出，可能可以發展聚焦在促進低NNNS分數之幼童的認知與注意的介入方式，或者以空間理解能力幫助他們。目前還沒有這些介入方式，但是，它們很可能被發展出來。
　　
　　作者們皆宣告沒有相關財務關係。
　　
　　Pediatrics. 線上發表於2009年12月7日。


Neonatal Scale Predicts Developmental Delays in Early Childhood

By Pauline Anderson
Medscape Medical News

December 17, 2009 — A scale that measures neurologic and behavioral problems in newborns predicts developmental delays later in childhood, according to a new study.

The scale — the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) — is better at predicting developmental problems in children up to preschool age than gestational age and socioeconomic status (SES), according to the study that compared outcomes of infants exposed prenatally to drugs with their unexposed counterparts.

The NNNS, which includes measures of such things as the ability to follow animate and inanimate auditory and visual stimuli, hypertonic responses, lethargy, and levels of arousal and stress, takes about 20 minutes to complete and can be administered by any trained medical personnel.

Picking up developmental problems early is important because research shows that children benefit most when they get help at a young age.

Although it is too soon to call for universal NNNS screening, it is something to look at in the future, said the study’s lead author, Barry Lester, PhD, director of the Brown Center for the Study of Children at Risk, Brown University, Providence, Rhode Island.

"Universal screening is only worth doing if, number 1, we know it works in other populations and, number 2, we’ve done the treatment studies to show we can effectively intervene and prevent the bad outcome," Dr. Lester told Medscape Psychiatry.

The study was published online December 7 in Pediatrics.

Drug Exposure

The study included subjects from the Maternal Lifestyle Study, a multisite, longitudinal study of infants exposed prenatally to drugs and born prematurely. This current analysis included 658 infants who were exposed to cocaine before birth. These children were compared to a group of 730 infants who were not exposed to cocaine who were matched for gestational age, sex, race, and ethnicity.

In addition to determining whether the infants had been exposed to cocaine, opiates, tobacco, alcohol, and/or marijuana and the level of such exposure, researchers gathered information on the infants' birth weight, length, head circumference, and intracranial ultrasound reading at 44 weeks.

The NNNS was administered at the 1-month clinic visit to 90% of the original infants (1248 of 1388). On the basis of the NNNS scores, the infants were grouped into 5 risk categories or "profiles," with those in profile 5 having the worst scores.

Compared with other infants, the 72 infants in profile 5 (5.8% of the total sample) had poor attention and were highly aroused, excitable, hypertonic, and highly stressed. These infants tended to have been exposed to alcohol and drugs prenatally and to have been born prematurely or had a low birth weight. More than 50% of them weighted less than 2500 g.

During the next 3 years, the researchers administered infant developmental tests, including the Bayley Mental Developmental Index and the Psychomotor Developmental Index. At the 3-year visit, the mothers completed the Child Behavioral Checklist (CBCL). At 4 years, researchers evaluated school readiness, and at 4.5 years, they measured IQ using the Wechsler Preschool and Primary Scale of Intelligence.

The study found that about 40% of infants in the profile 5 group had clinically significant behavior and school readiness problems and about 35% had a low IQ. In addition, a worrisome 42% had deviant total behavior scores on the CBCL.

About 22% of the infants fell into the profile 4 group, the next worst category. These infants had extremes in tone, the most nonoptimal reflexes, poor quality of movement, and a high number of stress signs.

When researchers combined profiles 4 and 5, they found additional developmental red flags. "If you add in profile 4, you do pick up a few more kids on different outcomes, but whether we use profile 5 alone or combine it with profile 4 will depend on how this plays out in different populations," said Dr. Lester.

Including only infants who had drug exposures and were born prematurely was a limitation of the current study. Dr. Lester and his colleagues are conducting other studies using the NNNS in different populations of infants in the United States and other countries.

Better Predictor

After controlling for gestational age and SES — 2 variables that also predict poor developmental outcomes — the NNNS still effectively predicted an abnormal ultrasound reading at 1 month in profile 5 infants (odds ratio [OR], 2.37; compared with other profiles), chronic neuralgic abnormalities (OR, 2.35), externalizing behavior problems (OR, 2.05), internalizing behavior problems (OR, 2.72), and total behavioral problems (OR, 2.37).

"We make the point that even if things like birth weight and SES predict as well as the NNNS, which they don’t, you can’t do anything about them," said Dr. Lester.

"You’re not going to change a baby’s birth weight and you’re not going to change a baby’s level of poverty, but the baby’s behavior is something you can work with and make a difference."

Picking up developmental problems and initiating preventive measures early on could optimize long-term benefits. "If we confirm that these profile 5 kids are headed for trouble at 4 years of age, perhaps we can develop an intervention based on that profile and see if the intervention can reduce or prevent the problems from occurring," said Dr. Lester.

Incorrectly Labeled

Like any scale, the NNNS is not perfect; it’s inevitable that some infants will be incorrectly labeled as destined to have developmental problems. Many children appear worrisome as infants but go on to develop normally.

Mislabeling an infant could create a self-fulfilling prophecy, with parents unintentionally treating their infant differently, noted Dr. Lester. "They may treat the baby as if it’s fragile, they may not provide the appropriate stimulation, or they may be very anxious. So you might be creating the very problem you’re trying to prevent."

However, he added, that the NNNS is noninvasive and early intervention is benign. He also thinks that parents should eventually have access to their infant’s NNNS results and decide for themselves what to do with that information. He likened it to the breast cancer genes BRCA-1 and BRCA-2. "If you have a gene that makes you more likely to have breast cancer, you should be entitled to that information and decide what you want to do with it."

Impressive and Important

In commenting on this research, Joan Luby, MD, professor of psychiatry, Washington University School of Medicine in St. Louis, Missouri, and chair of the Infant Preschool Committee, American Academy of Child and Adolescent Psychiatry, Washington, DC, called the findings "impressive and important."

The results should go a long way toward filling the "black hole" that exists around the question of which newborns will run Into difficulty later on, said Dr. Luby. "More research needs to be done, but this provides a key piece of the puzzle."

It might be possible, added Dr. Luby, to develop interventions that focus on enhancing cognition and attention in very young children with low NNNS scores or helping them with spatial skills. "Not that these interventions are currently available to my knowledge, but it’s certainly very, very plausible that they could be developed."

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online December 7, 2009.