Neonatal Thyroid Deficiency: Early Temperamental and Cognitive Characteristics

Neonatal Thyroid Deficiency: Early Temperamental and Cognitive Characteristics ,JOANN E F. IW VET , PH.D., DONNA-LE E WESTBROOK, D.C.S.,

AN D

HOBE RT M. EHR LICH, M.D.

Si xty-ni ne children wit h conge nita l hypoth yr oidism detected t hro ugh th yroi d sc reen ing were compared wit h ;{9 un a ffected siblings for cognitive and temp eram en tal characterist ics. Int elligence test resu lts revealed: (1) IQs of hypot hyroid children were normal but lower t han siblin gs; (2) hypothyroid childre n were lower than siblings in gross moto r an d perceptual performance abiliti es; (3) at hyr otic children had lower IQs tha n t hose with ectopic t hyroids, goite r, or hypoplasti c disease; (4) at hyrotic, hypoplast ic, and ecLopic thyroid children had lower performance than ver bal IQs, but there was no scale difference for t hose with goit er; (5) deficits differed according to test age; and (6) age of on set of t reat ment was not relat ed to IQ or pattern of deficit . T emperam ent tes t findings revealed: (J) no increase in difficult. or slow-to -warm-up children, (2) lower ratings were found for hypothy roid children t ha n siblings on approach/ wit hdra wal and persiste nce scales, and (3) higher rati ng was given for athyrot ic chi ldren t han t hose with goiter. J ourn al of the American Academy uf Child Psychiatry, 2:{, 1:10- 22, 1984.

Congen it al hypot hyroidism (CH), also known as cretin ism (Crome a n d St ern, 1972) is a relati vely comm on disease of newborns. Cause d by t he lack of su fficien t t hyro id hormone t o meet the body's daily needs, ClI , if u nt reat ed , will lead t o irr eparable brai n damage a n d severe p hysical a nd men tal ret a rd a t ion (S mit h et a l., 1957). Recen t st at ist ics sho w t hat CH occurs in about 1 in 4,000 (Ca ha la ne a nd Dockera y, 1982; Con ne lly, 1982; Delan ge, 1980 ; F ish er, 1975; .Iohn and W oodh ead , 1982) to 1 in 6,000 live bi rths

P rim a ry C H ca n occu r from an ab sent thyr oid gla nd or at hy ros is; an undescended , ling ual or ectopi c gla nd ; en zyme defect s causin g goit ers , a nd mal formed or hyp opl ast ic gla nds, correctl y located. Price et al. (1981) rep ort t he follow ing incidence figur es for primary CH: athy ros is, 25%; ect op ias, 29%; goite rs , 29%; hypoplasias, 17%. Alt ho ugh h ie (1980 ) provides sim ilar figu res for .Iapa n , ot he r region s cla im a lowe r in cid enc e for goite rs (Ca ha la ne a nd Dock era y, 1982; Mathur et al. , 1982; Suthe rla n d et aI., 1982). It has

( Lrio, 1DHO ; Mitch ell d n l., l D7H), n lt h o u g h some cs f.i-

b een s u gge s t.e d t.luit. ec to p ic a n d go it.ro u s h yp o t.h y ro id -

mat es even range as low as 1:2,400 (Morreale de Escobar et al., 1982; W alfish et al., 1982). Con gen it al hypothyroidism ca n occur from a defect ill the thyroid gland (pr imar y CH ), dysfunction in the pi t u it ar y glan d (secondar y CH ), dysfun ct ion of th e hyp ot ha la mus (te rti a ry CI-£) or from a nu mber of en viron menta l factor s suc h as t he lack of iodine or expos ur e t o goit rogens. Iodine insu fficien cy produ cing en demic cr etin ism occurs p rimarily in pop u lat ion s in develop ing na ti ons (De lan ge, 1982; E rrnans, 1980; K ochupillai et al., 1982) or na t ion s whe re salt is not iod ized (K lett et al., 1982).

ism may represent less severe forms because t here may be some mi ni mal fu nction al thyroid act ivity a t birth (Klein, 1980 ). T he thyroid gla nd is locat ed at t he base of t he neck . It se rves to p roduce two t hy ro id horrnones- - t ri iodot hyro n ine or T ;l and tctraio dothyron ine or T 1 , also kn own as t hyroxin e. T h is is acc omplished by t ra pp ing circulating iodi n e in t he t hyroid gla nd, hen ce t he need for appropriate iodine cons u mpt ion. T a is t he active hormon e, wher eas '1'4 is a "proh or mone" which becomes acti ve on ly when it loses on e of its iodine molecul es at t he target ti ssu e sit e. The sy nt h esis a nd sec ret ion of T, and T:J are regulat ed by t hy roid st imulat ing hormone (T SH) whi ch is p roduced in a nd secret ed by t he pi t uitary glan d. '1'SH regu lation is in turn contro lled by a peptide produced in t he hyp ot hal a mus, kn own as t hy rot rop in releasing horm on e (T R H) . T he production of T RH a nd T SH is cont ro lled by a n egati ve feedback of circu latin g '1'1 a nd T:l at t he level of t he hypot halamus and t he p ituit ar y glan d . Thyroid hormones a re t ra nsp ort ed in the blood st rea m bound to a nu mber of proteins. They h ave a

Th is rcsca rcli was supported by an Ontario M in istry of Health l Jc>vC'lopnwnt grout, IJlvI15/ , and th e Researcli Institute of the Hospital for Sicl: Children . T he authors wish to thank Paul Walfish, N eville l linnanl, Chuch Netley , J aqucline Glorieux, J eann ine Pin son neault and the Word / 'rocess in~ Centre for their individual contr ibutions to tlu s paper. Portions of th is paper were present ed at th e Se cond l ntcrnat ionai Meetint; 0 /1 Neonata l Th y roid Scr eening, '1'0llyo. A ugust. 1982. Itcp rin t» may be requested from J oanne F. Hovel, Ph.D., Psychol0kY Depart ment, T he Hosp ital for S ick Chi ldren, 555 Uni versity A vellue, To ronto, Ontario, Canada M5G / X8 . 000 2-7 1ilH/ H4/ 2:101-0010 $02.00/0 @ HlH4by the America n Acad emy of Child Psychiatry . lO

NEONATAL TH YROID DEFI CIENCY

mul ti tude of effects on t he growth, differ en ti ati on , a nd fun ction of ma ny tissues in t he body. Acco rdi ng to Fi sh er (1980) "thy roid hormon es, while imp ort an t at any age to maintain body met ab olic homeost asis, are critical durin g ch ildhood to control the ma ni fold mat ur ation al events and the t ransformation of the newborn to the mature adult " (p. 67). Conge n ital hypothyr oidi sm is read ily treat ed by the dail y or al ingestion of L-thyr oxine, a t hy ro id hormon e (Abbasi a nd Aldi ge, 1977; Redmon d, 1982; Rezv anz i a nd Di Geor ge, 1977) . Studies have show n t hat if t hy roid h orm one repl ac ement t he rapy is begun before the third month of life, ment al retardation can be prevented (Ge sell et al., 1936; Klein et al., 1972; Smit h et al., 1957), a lt ho ugh IQs tend to be lower t ha n ave rage an d ther e is an in creased risk of subsequent learning diffi cul ti es (M ac Faul et al., 1978; M on ey, 1956; Re ed an d Lavecchi o, 1980; Va nde rs hue ra n -Lodeweyckx et al., 1980), behavior al problem s (M acF aul et al., 1978; Mo ney, 1956), an d unspecified n eur ological disorders (An derse n, 1975; Ma enpaa, 1972; Vandershuer an -Lodeweyck x et al. , 1980; W olter et al., 1979 ). Further more , outcome a nd age of di agn osis appear to be negati vely correlated such t hat the la ter the diagn osis, t he more se rious t he problem (Kap la n, 1980; MacF aul et al., 1978; Vander shueran -Lodeweyckx et al., 1980) . Ma cFaul et al. (1978 ) h av e also shown that whi le nonverbal spatia l de ficits are appar ent from birth, verbal deficits a re mos t susceptible to delays in t reatme nt . T he p roblem , however , is t ha t t he outward signs a nd sy mptoms of neonatal thyroid hor mon e deficien cy ta ke ti me to develop. Most CH in fa nts a re hea lthy a nd appea r qu it e "normal" wh en they are born (An der sen, 1975). In fact , many CH infan ts do not present a ny clinical signs un til as lat e as 8 mon ths of age . Unfortunately, t his mea ns t hat by t he ti me a clin ica l diagnosis is mad e a nd treat ment is given, irr ever sibl e brain da mage may ha ve occur red (Ande rse n, 1975; Ge sell et al., 19:16; Hall and Scan lon, 1975; K enny et al., 1975; Myant, 1971 ). Ther e a re a nu mb er of studies which show that t hyro id horm on e is esse ntial for nor ma l br ain develop ment (E ayrs, 1956; H a mburgh and Fl exn er , 1957; Myan t, 1971). P resen t evidence suppor ts th e concept t hat t hyro id hormon es direct brain ma tura ti on by affe cting cell differ entiation , particul arly durin g the most active phase of t h e b ra in growth spurt , wh ich occurs both fetall y a nd in ea rly neon atal life in t he hum a n infant. It is t ho ught t hat t hy roid horm on es somehow convey a message t o t he developing brain to te ll it when to stop div idin g a nd start diffe rentiatin g as t o spec ific functions (Morreale de Escobar and E scobar del Rey , 1980) . T he cerebe llum , whi ch has it s

11

most active ph ase postnatally (Dobbing a nd Sands, 1973) , is espec ially vulne ra b le to a ny in sul t , in cludin g CH . Wi th t he exceptio n of one postmortem study by Benda (194 1), t he majori ty of t hese inv es t igations hav e been ba sed on animal models, prim a rily t he rat. T he se st udies indicate th at thyroid hormon e has a n effect on cellular a rc hitectur e (cell size, cell number ), vasc u la rity, myelinizat ion and dendriti c formation (Bal azs et al. , 1971; Brasel and Boy d, 1975; E ayr s, 1960, 1966, 1971; H amburgh et al., 1971; Mi t sk evich and M osk ovin , 1971). Recent studi es of hyp othyr oid macaque mon keys al so reve al tha t t hyroid ho rmon e deficien cy affects RNA a nd protein sy nt hes is, particularly in t he produ cti on of enzy mes in volved in glia l cell an d myelin development (Che e k, 1975; H olt et al. , 1975). The role of t hy ro id hormon e in human fetal develop me nt is no t entirely kno wn al though useful in formation is currentl y bein g gained fro m pret erm infants (Fisher , 1982). It is clear t ha t the fetus's need s cann ot be met by maternal t hy roid hormones becau se t he p lacen t al barrier appears to be impermeab le to t hyro id hormon e (Bur row, 1982; Fi sher, 1975; She pa rd, 1971). Ther efor e it is not known to wh at degree thyr oid defi cien cy affects brain development in intra ut erine life. Over t he pa st decade, te chno logical advanc es in assayin g a nd collecting t hy ro id hor mon e from sma ll sa mp les of blood spotte d onto filte r p ap er (Chopra, 1972; La rse n a nd Rros ki n, 1975) have allowe d for detection of CH in la rge sa mp les of newborns (Dussault et al., 1975; Walfish, 1975). Because of the suc cess of the early pil ot programs in ident ifying CH children and p reventing t he ir men tal ret ardation by t reating t he m soon aft er birth (Duss a ult et al., 1978; Illi g, 1979; W alfish et al., 1979), manda tor y ma ss screen ing programs have now been est a blishe d in many pa rts of t he world. Th is incl udes so me provin ces in Ca nada (Du ssault et al., 1982; T hores et al., 1979), most stat es in t he United States (Klein, 1979; LaFranch i et al. , 1979; Mitch ell et al., 1978), the Un ited Kingdom (Ca rso n et al., 1982; Hulse et al., 1980), Austra lia (Co n nelly, 1982; Robert son et a l., 1979), E urop e (Dela nge, 1 97 ~) ; Fa rri au x a nd Dh on dt , 1982; Meijer , 1982), .l apa n (Na ruse et a l., 1982) an d Scan dinavia (Larsson et al. , 1981) . Gu ide lin es have been established with few differ en ces between t he variou s program s (De la nge, 1980 ). These progra ms now operate efficiently a nd in expen si vely (Lay de et al., 1971J), often in conjun ction wit h screen ing program s for ot her metabo lic diseases such as ph en ylk etonuria or PK U (Dho nt, 1982; T he rrell, 1982). Acco rding to Burrow and Dussa ult (1980) thi s represents on e of the few

12

RO VET ET AL .

ar eas of mod ern medicin e whe re adva nce in medical pr ogress has clearl y had a maj or impact on socie ty. The t yp ical pr ocedures in thyroid screen ing ar e t o spot a few drops of infa nt serum onto filter pap er collected seve ra l days after bir th . This is then mail ed t o a centra l lab or atory where t he blood is ana lyzed eit her for 1\ (e.g. Dussault et al., 1975; Klein , 1979) or TS H (e .g. Delange, 1979; Walfish et al. , 1979) or both (LaFra nchi et al. , 1979). Assayin g for TSH has a sma ller false -pos it ive rate but misses detecting seconda ry or tertiary types of hyp othyr oidism (which are ra re). Assay ing every neonate for both hormones, though most accur ate, is costly. All positiv ely identified cases are subse quently recalled for confirmato ry diagn osis, at. which poin t t reatment is begun. This usually t ak es place within t he infants' first month of life. Recently a number of pr osp ective investigations of positi vely identified CH cases have been undertaken . The genera l conse ns us is that mental retardation is bein g pr even ted by early dia gnosis and treatmen t du e to neonatal scree ning (Arno ld et al ., 1981). The majority of st udies show IQs well within the normal ran ge, with lower scores occurring in only a few cases (Arnold et a l., 1981; Du ssaul t et aI., 1980; LaFranchi , 1980; Rochi ccioli, 1980). Unfo rtunate ly, becau se ther e is no standa rd assessm en t protocol across the various studies as to test measures, test ages, or type of control group (if used at all), there is no con sensus as to the spec ific outcome of ea rly t hy roid deficiency. For exampl e, Du ssault et a1. (1982) reported no differen ce between C H childre n a nd normal contro ls at l ~ months usin g th e Griffit hs test (see also Dockeray et al ., 1982), where as Reed and LaVecchi o (1980) using the Bayley scales of infant development report that CH infan ts scored significantly lower in psych omo tor asp ect s of performan ce. Du ssaul t et al, (1982) did find that by 36 mon th s CH in fan ts wer e scoring below con trols in both ver ba l and perc eptual scales. Similarly, Rochi ccioli et a1. (1982) noted a stea dy declin e in performan ce wit h increasin g age, particularl y for lan guage skills. These findings may refl ect a t rue decline in ability with age or may be du e to t he greater sensitivit y of intelligence test items wit h older childr en . Ther e are a number of inher ent diffi culties in t hese prosp ecti ve studies . In many, fact ors such as et iology of t hy roid disea se, compliance, init ial t hy roid hormone levels, genetic , environmental, and other disposit ional factors su ch as temperam ent have not been syste matically accounted for in t he resul ts. For example, in vestigati on s of clinically dia gnosed (i.e. un screen ed) CH child re n cla ssified according to et iology of th yr oid disease indicate t ha t IQs are lower for athyrotic cases

t ha n those with goite rs and ecto pic or hypoplasti c gla nds (Ande rse n , 1975; Kaplan, 1980; Kenny et al., 1975 ). This su ggests a relation ship between amount of func ti oning t hy roid tiss ue and intellectu al outco me. Of greater inter est, however , is th e possibility of an interaction bet ween t reatme nt age and et iology with IQ. Th is is based on Klein 's (1980) review of t he liter ature which showed t.hat. whereas at.hyrot.ic cas es ben efit ed from imm ediate t rea t me nt, those with goite rs demon strated better resul ts if a slight delay was allowed. Klein attributed t his in tera cti on t o t he amount. of fun ctioning thyr oid ti ssue, suggesting t hat it might, in fact, be best t o delay t reat ment for several months if there was so me thyro id ti ssue present. This issue certainly needs furthe r clarification, pa rticularly with CH infants and childre n iden ti fied by scree ning where large samples a re avail abl e, diagnoses ar e made ea rly, and t re atment is adm inistered as soon as pos sible regardless of eti ology. A seco nd issue conce rns behavioral fact or s ot her t ha n in telligen ce whi ch ma y be affect ed by conge nital hypothyroidi sm . These factors could also a ffect in ter personal relation s and qual ity of learning at sch ool. These tend to be neglect ed in t he majo rity of followup in vesti gation s of CH children despite t he ir kn own impo rta nce in learn ing and t he fact that a few retrospect ive studies of un scree ned CH childre n did reveal specific behavioral abnormalities . For example, Mon ey (1956) repo rted that CH individu als wer e t yp ically lethargic, indiffer ent, and lacking in dri ve, even if t reated early . MacF au l et al. (1978) claimed an u nusually high incidence of b ehuvio rul d evianc e among CH children, with increas ed restlessness, poor attenti on and excessive fea rfulness being common symptoms. These gene ralizations were based primarl y on clinical impression and not on a syste matic inv estigation of t he te mperamental or persona lity cha rac te rist ics of CH childre n. T here is also some cont roversy as to whet her breastfeeding ca n, in fact, provide some pr ot ect.ive ben efit for t he CH in fant, while also ma sking early clinical recogni ti on (Sack et a l., 1979). This is because human milk may con tain va riable quantities of t hy roxine (Obe rk otter et al., 1981) . Sever al papers dire ctly addr essing t his issue report conflicting results, showing eit her no benefit (Letarte et al. , 1980) or a partial benefit (i.e. for boys only) (Banga li, 1981) of breastversus bottle-feeding. Ot her issues concern t he genet ic and demogr aphic cha racterist ics of the samples invest igated. Do the resul ts obta ine d reflect t he sa mple charac te ristics and not t he t rue effect of t hy roid deficien cy? For example, are bri ghter paren ts more willing to comp ly with both t.reatment and follow-up investigat ion? What ar e the

NEONATAL THYROID DEFI CIE NCY

effects of soc ioecono mic status a nd specific ch ild rearing practices on outco me in CH childre n? Are t he pa ren t s of CH children consc ious ly or unconsciously atte nding more to t he CH chi ld an d in doin g so compe nsating for pot en ti al di fficul ti es ? Anothe r qu est ion conce rns what constit utes a n app ropriat e co ntro l group for a prospective in vesti gat ion of CH chi ldre n . This is consi dered an important factor in assessing t he effects of a ny congen ital abnor mal ity (Garron, 1977). P revious in vesti gati on s of CH ch ildre n have involved nonrelated normal childre n match ed for age and soc ial back ground (Dussault et al., 1978), false positives (Arnold et al., 1981), and siblings (Arnold et al., 1981). Each is less than ideal : unrelat ed, unaffected n ormal chi ldre n matched for age allow for comparison s on iden ti cal t est measures bu t suffe r fro m (a) the confo un di ng effect of intra-familial (both gen etic and experiential) differences, (b) se lec tio n biases regarding conse nt (Bur row , 1980) and (c) qualitatively differ en t attritiona l biases. Paren t s of false positi ves who consent to p ar t icip ati on an d follow-up in vesti ga ti on of t h is kind may thems elves represent a select group, given t he rep or t ed anxiety a nd stra in t hese paren t s a re know n to suffer prior to learning t he ir ch ild is nor mal (T hieffry et al., 1982). Siblings differ in (a) age, a nd so n ecessitate t he use of differen t test procedures, (b) sex , whi ch cou ld skew the resul t s for ta sk s which a re se nsitive t o sex- related di fferen ces (M acco by a nd Jacklin, 1974), a nd (c) birth orde r. Neve rthe less, sib lings have the ad vant age of similar genetic and soc ial backgrou nd factors, which so stro ngly affect te st sco res. Hines (1982) recomme nds utilizing siblings in psychoendocrin ological research, particularly wh er e pre n at al hormone influences a re concerned. The present study was designed t o deal with man y of t hese iss ues in a relat ively large sa mp le of ne on ata lly screened CH in fa nts a n d childre n. It s goal s were to determ ine t he spec ific a bility levels of CH ch ildre n ac ross a wide range of psych ological fun ctions in comparison to siblings a nd accordi ng to eti ology, to det er min e the relati on ship s between t reatme nt onset a nd spec ific abilit ies, to assess t he te mpe rame ntal a nd behavior al cha racteristics of CH childre n, and to assess wh ether brea st feed ing provid es a prot ecti ve ben-

was lat er expande d to serve all othe r T or on to hospi tals. This program , whic h is sti ll in effect today, in volves t he assay of T SH fro m cord blood. The seco nd program, run by t he Ontario Ministry of H ealth , is a routine mass sc ree n ing program of all newb orns in t he province on On t ario (T'hores et al., 1979). Begun in late 1978, t his program in volves the assay of 1'4 (late r switche d to TS H) from infa nt se ru m obtained via heelprick s usu all y on t he fifth da y of life. The two progra ms ope rate concurren tly a nd independentl y, with the first serving as a chec k on the sec ond (Wa lfish et al., 1982). In the provincial program , all positively identified cases are immediately n oti fied and reassessed at one of six regional center s for con firmat ory diagnosis. In t he bro ader Toronto area (whic h covers almost hal f of t he Ontari o newborn populat ion ), the region al ce n te r is t he H ospi tal for Sick Childre n , also t he cen te r for t he cord program . Confi rmation in volves repeat blood tests and t echnetium -99 scans to establish etiology, a procedure not ty p ica lly carr ied out on newborns in man y program s (e.g. Quebec (Dussault et al. , 1982)). T reatment is begun at t he in it ia l visit and t he chi ld is routine ly followe d at regular intervals t he reafter. T he psycho logica l evaluation com pone nt is arrange d independently of t he medi cal assessme nt bu t ofte n occurs wit h a sc he duled endocri ne appo intme nt.

efit.

fe ma le , n o n-C t l m al e ; -1 C I I m al e , lI oll -ell fe ma le) .

Th is study in volves t hose CH ch ildre n who a re cu rre ntly be ing t reated at t he Hospi t al for Sic k Chi ldren in T or on t o. The pa rti cular sa mp le was ident ified t h rough on e of two sc ree ni ng progra ms t ha t are curren tly in ope rat ion in On t ar io. One program whi ch is local , based primarily in t he city of T oronto, was begun in 197:3 at the Mount Sinai H ospital under the dir ect ion of Dr. Paul Walfish (W al fish et al., 1979) a nd

F ift y-five parents (42 moth er s, 1:3 father s) wer e assessed for intelligen ce. All 69 fa mi lies were assessed for socioeco no mic status .

Method Subjects The CH samp le cons isted of 23 boys an d 46 girls. For ty -eight of the ch ildren wer e of Caucasian origi n (in cluding 4 East Indians), 10 were black, 5 Ori en t al , an d :3 of mixed racial origin. Technetium scan s revea led that 16 (2:3 %) had absent thyroid glands (at hy rosis), 22 (32%) had goiters or enzyme defects, 28 (41%) had ectopic thyroids (2:3 lin gual, and 5 mal descent) a nd 3 (4%) had hyp opl asti c gla n ds correctly locat ed . The sa mp le in clud ed 1 set of siblings a nd 1 pa ir of mon ozygoti c twi ns. The :39 non hyp othyr oid sib lings co ns isted of 21 brothe rs a nd 18 sisters (mea n age = 5.7 yea rs, ran ge: 3- 15 yea rs). The majori ty of si blings (87 %) were older t han the CH ch ild . Th er e were 21 sa me sex pairs (111 sisters, 7 brothers ) a nd 18 cross-sex pairs (14 CH

T est s Intelligenc e. Those subjects wh o were less than 5 years of age wer e t est ed with t he Griffiths Scales of Mental Development (1954, 1970), while those wh o

14

ROVET ET AL.

were G or older were given the age appropriate Wechsler test (1967,1974). Parents received a short form of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Wechsler, 1981). The Griffiths Scales (19M, 1970) evaluate a child's developmental status in a number of specific areas of intellectual functioning and across a relatively wide age range. Until age 2, items cover five major areaslocomotion, personal-social, hearing and speech, eyehand coordination and performance (e.g. block-building) abilities-while after age 2 a sixth scale, practical reasoning, is added. The test yields both a global quotient of intelligence as well as individual quotients for each of the five or six subscales. Major advantages of this measure over other infant intelligence tests are the number of separate factors that are assessed, and hence the broad spectrum of abilities that are scored, as well as its sensitivity to the functioning of relatively young children. There is some evidence to show that early ability patterns on the Griffiths do predict later skills (Lister, 1979). A disadvantage of the Griffiths, however, is that its norms may be inappropriate for Canadian and American children because they were based on British infants and children (Ramsay and Fitzhardinge, 1977). The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Wechsler, 1967) was given to children between 5 and 6 years of age. This instrument, which contains a number of subtests, provides :3 coefficients of intelligence: verbal intelligence (VIQ), performance intelligence (PIQ), and general or full

5) intensity level of reactions, 6) quality of mood, 7) persistence, 8) distractibility, and 9) threshold of responsiveness. Age appropriate means and standard deviations are supplied with each measure. Responses are scored so that high scores reflect positive temperamental characteristics while low scores reflect those that are negative. In addition, criteria are provided so that response profiles on the first 6 scales can be used to characterize a child as "easy," "slow-to-warm-up," "difficult" and "intermediate-low" or "intermediatehigh." The Infant Temperament Scale (Carey, 1972) is appropriate for infants from 4 to 8 months; the Toddler Temperament Scale (Fullard et al., 1983) for children from 12 to 36 months; the Behavioural Style Questionnaire (McDevitt and Carey, 1978) for children 3-7 years of age; and the Middle Child Temperament Questionnaire (Hegvick et al., 1981) for children 8-12 years of age.

Socioeconomic Status This was assessed using the Hollingshead Four Factor Index of Social Status (Hollingshead and Redlich, 19G8). This index is derived from information about parental occupation, education, sex and marital status which are rated according to set criteria. A score of 15 (l = high) is assigned based on the cluster value of the composite rating.

Procedure

scale intelligence (FSIQ). Af't.e r G years, children were

The ideal protocol would have been to follow a

given the Wechsler Intelligence Scale for ChildrenRevised (WISC-R) (Wechsler, 1974). This test is comparable to the WPPSI, also involving multiple subtests that measure VIQ, PIQ and FSIQ. Parents were given the WAIS-R Vocabulary, Similarities, Object Assembly and Block Design subtests and a prorated FSIQ was determined.

cohort of children on a regular basis who would enter the program at exactly the same age. However, because this study began a number of years after the screening programs, the children varied in age, with many older than the criterion starting age of 12 months. Therefore, our procedure was to first see the child when he or she was as near to one of the prescribed assessment ages and then to continue following him or her on a regular basis thereafter. The procedure differed for those children born after the study began. Their parents were initially contacted when the child was 6 months old, the project was described, and they were asked to complete several questionnaires, including the Carey Infant Temperament Scale (Carey, 1972). The specific assessment ages for the CH child were 12 months, 18 months, 24 months, 3, 4, 5, 6 years and so forth. The sibling and the parent were tested only once, at the CH child's initial visit. Table 1 shows the number of CH children who have been assessed at each test level age. Also included are the number of 6month-olds about whom only parent-report information on temperament was obtained.

Temperament The age-appropriate Carey Scales were used for this purpose. These are questionnaires completed by the parents requiring them to rate how their child typically responds in a number of different commonly occurring situations. Each of the scales consists of approximately 100 items which form the basis of 9 temperamental categories derived from the original New York Longitudinal Study on temperament (Thomas and Chess, 1977). The 9 categories are: 1) activity level, 2) rhythmicity (i.e. periodicity in feeding and sleeping schedules), 3) approach or withdrawal as initial response to new or altered situations, 4) degree of adaptability to altered environmental structuring,

15

NEONATA L TH YROID DEFI CIE NCY TA BLE I N umb er of A ssessments --- "...

. __._-

CH Ch ildr en T est Age

Male

Fema le

_ . _ -- ---- ----.---.

.... -

T ota l

- -

.

9

2

8 (l )h

1 ;~

(6)

(3)

11 (8)

4 (3) 4 (1) :\ (0)

12 (4) 10 (2)

[j

:I

2

4 ( 1) 4 1

11 21 16 16 14 7 7 3

(7) (11) (7) (3) (1)

3 6 2 2 2 1 4

0

_-

- - _..

Ect opic

Ath yrot ic -- -- -

6 moo 12 mo 18 mo 2 yr 3 yr 4 yr 5 yr 6 yr

-. - _.. _ -- -

.---- -- -

- _._.

Sib lin gs

By Etiol ogy

By Sex

...

_---- -

- -_

..•

Goite r

Hypoplasia

Unknown

No.

...._ - - ---

-- -----

6 9 5 8 4 3 1 1

. .._---

2 6 9 6 7 3

---.-.-.

1 1

._._-----

---

0 0 0 0

0

1 0 1 1

0

Mean age (yr)

N/A

0

1 :~

0 0

;~

0 I" 0

fi.G 6.0

6 4

s.s

fi fi

7.4 4.6

:~

6 .:~

4.8

Con genital hypo t hyroid child not seen at t his age, parent report data only. Number in pa rent heses rep resents numher who ha d earlie r assessments. c T his chi ld move d to st udy from a differ ent province where tec hnet ium scans not given.

a

h

TA BLE 2 Parent / Q and S ES Across Groups

Data A na lysis

Dependen t t-tests were used to compare t he data of CH children and siblings in a match ed pa irs design. These resul t s conce rn only t hose children with par ti cipating siblings . Ana lysis of cova ria nce tests (ANC OVAS) with par en t IQ and SES as cova riates were used to compare the different eti ological groups. Those parent s wit h missing IQ values were assigned t he over all mean parental sco re. R esults T able 2 shows t he mean pa rental IQ and SES scores for eac h of t he differen t groups . Analyses of va riance ind icated t hat t he four t hyroid groups did not differ from eac h ot he r on eit her index, F(3,5 1) = 1.33 and F( 3,65) = 1.43, respecti vely. Intelligence

The Griffit hs test was given to 48 subjects, t he Wechsler series to 1;3. A compa rison of Gri ffiths GQ scores wit h Wec hsler FS IQs revealed t hat t he scores were not differ en t for t he two tests ( p > 0.05). T he test scores were t he individual quotients for t he 5 (or 6) Griffiths sca les (refe rred to as AQ, BQ, CQ, DQ, EQ and FQ); a gene ra l IQ (GQ) base d on eit he r t he Gr iffith s gene ra l quotient or the Wechsler Full Scale IQ; a verbal IQ (VQ) based on the mean ofthe Griffit hs CQ (hea ring and speec h ) and FQ (reasonin g) scale

SES

IQ

Group Athyrotic Goiter Ectopic Hypo plast ic

N 16 22 28 3

Mean

s.n.

Mean

s.n.

96.8 97.2 99.7

10.8 15.1 19. 1 14.8

2.50 2.71

L09 1.09 0.86 0.56

92 . ;~

;~.O O 4 . ;~ ()

t ha n t heir siblings on t he Griffit hs GQ, and t he Griffit hs AQ (locomoto r) and EQ (performa nce) sca les ( p < 0.00l), as well as PQ (p < 0.002) combined across Griffit hs and Wechsler tests. T hu s, t hese da ta indi cate t hat desp ite the relatively high IQ levels, CH childre n do score lower than t heir non affected siblings in locomotor and perceptual motor areas. Etiological Comparisons. Fi gure 1 shows t he IQ frequen cy distribut ions of the 4 hypothyroid groups. This revea ls t hat the distribut ions are norm al for t he :3 major groups (i.e., athyrotics, ectopics a nd goite rs), with t he distribut ion bein g shifte d downward slightly for the athyrotic group. The data were combined for ma le and female subjects, given our preliminary findi ng t hat t he re were no significa nt sex differ en ces in t he data ( p > 0.05). T he data were ana lyzed separate ly by test age, given our ea rlier observati on (Rovet et aI., 1982) of different ab ilit y patterns for cert ain test ages. Although sepa -

sco r e s , o r t he W e c h sl e r (VTQ ); nnrl a per fo rm an c e TQ

r a t e n n al y s e s hy j'e st a ge in v ol v e d s m a ll samplo s iz e s ,

(P Q) based on th e mean of t he Griffit hs DQ (fine motor coordination) a nd EQ (performance) sca le sco res, or t he Wechsler P IQ. The mean GQ, VQ, and P Q scores of t he entire CH sample are 109 (S.D. = 11.58), 109 (S.D. = 15.2) and 104.7 (S . D. = 11.2), eac h clearl y within t he norm a l ran ge. Sibling Comp ariso ns . T hes e resu lts are given in Table 3. CH children obtained significantly lower scores

t hereby increasin g t he risk of'.a type II erro r (Cohe n, 1977), t hey did permit inclu sion of repeat test scores for t hose subjects ass esse d more t ha n once. For 12-month -olds, a 3 (group) X 5 (scale) ANCOVA showe d significa nt sca le, F(4 ,72) = 5.00, p < 0.001, and group X sca le, F(8,72) = 2.12, p < 0.05, effects . These wer e due to t he low fine mot or coordina t ion (DQ ) a nd per forman ce (EQ ) scores of the athyrot ic, ectopic and goiter groups as well as to t he relatively

IG

RaV El' ET AI.. T AB L E :J Congenital Hyp othy roid (CH)-S ibling Comparisons in I ntelligence

CH

N o. of Pairs

Scale

._-

108.4 112.4

10 3

111.8 105.4 109.0 136.0

16.1 21.6 16.6 17.7 9.9 23.0 20.7

121.0 124.4 114.5 121.9 110.9 120.9 127.7

18.8 12.3 41.5 31.8 24.4 24.3 19.2

-2.13 -0.62 -1.68 -0.81 -5 .04 2.54

NS 0.000 NS

39 :i9 iJ9

107.3 104.3 10'7.3

16.1 12.7 12.0

108.6 111.2 111.3

16.6 15.0 15.5

-0.53 -3.26 -1.97

NS 0.002 0.06

10

Personal-social (BQ) Hea ring a nd speec h (C Q) F ine mo tor (D Q) Performance (EQ ) Reas oning (FQ) (;riffith s, WP PSJ, WIS C-H VQ

PQ FS J(l

~

u

107.7

•

ur -,

Athvro uc

E2l Ec to p u: lllI Hypop lasia

:, m

~

10 10 10

o Go ue r

GO

40

o

1- '

Z

w

~

w o,

/0

8 1 90

9 1 100

10 1-11 0 . 111 120

p

S.D.

10

Locom oto r (AQ)

... . . _ - _.-.. ..

Mean

_... ...._ -- ---_ .. . -.

(; riffi I hs Only CQ

Non -CH

-_._ ._...

12 11 3 0

13 1· 14 0

FIG. 1. IQ distributi on s accord ing to et iology.

lower bearing and speech (CQ) scores of t he goit er group (see Table 4). For the 18-mo nt h asses sment , sca le and group X sca le were again significa nt, F(4,48 ) = 13.44,p < 0.001, a nd F(8,48 ) = 4.44, P < 0.001, but t his time reflect in g high performa nce (EQ), high locomotor (AQ) and low personal social (BQ) scores of t he :3 groups combined, as well as low hearing and speec h (CQ) and fin e mot or coo rdinat ion scores (DQ ) of athyrotics. At.24 mon ths, there was a significant effect of sca le, F (5,45 ) = 9.79, p < 0.001, due to t he lower fin e motor coo rdina t ion (DQ) values of t he 3 groups . Hearing and speec h (CQ) and performance CEQ) scores also tended to be lower for the athyroti c group t han the goit er or ecto pic groups at this age. Each of the 3 group s demons t ra te d relatively high levels of performance in pract ica l reasoning (F Q), which is added to t he protocol at t his assessment age. At :~ G months, th e onl y effect significant was sca le, F (f),40) = 9.40, p < 0.001. This ref1ected the low hear in g and speech (CQ) and fine motor coord ination (DQ) of scores of t he combined group, and to a lesser degree, the low performa nce scores (EQ) of the athyrotic an d ectopic groups. There were too few 4-year-

_.--

- ----

Me an

-- -

S.D.

- _.. . .. _ ---_..

- 3.49

0.007 0.06 0.55

NS

olds assessed to permit compara ble analysis of the data. In sum, these resul ts indi cate that, except for the 18-month assessment, t he groups demonstrated defi cits in fine motor coordination, performance, and hearing and speech with t he lat ter most obvious for goit rous cases . VQ and P Q scores (i.e. from Griffiths and Wechsler dat a) were compared for the total sample combined, regardless of test age, with the ini t ial set of scores being used for those subjects assessed more than once. These data were analyzed by a 4 (group) X 2 (sca le) ANCOVA. The results reveal ed an effect of sca le, F(l,55) = 11.54, P < 0.001, due to the generally lower PQ than VQ values (see Table 5). Also significant was the group X scale interaction, F(3,5 ) = 2.98, P < 0.05, which reflected the lack of differen ce bet ween scales for subject s with goiters. Relat ionships with Tr eatment Age. Partial correla tions were comput ed in orde r to assess whether treatment age and IQ ar e related in neo natally screen ed child ren. The effects of parent IQ and SES wer e removed from the correlations. The mean age of onset of treatment was 22.8 days (S . D. = 24.7 days; range 539 days plus t wo outlyin g values of 91 and 145 day s) for the ent ire group. For athyrotics, treatmen t was begun at 24.0 days (S.D. = 23.6; range 9-145 days) on the average, for t he ecto pic group , 18.7 da ys (S.D . = 17.9; range 5- 39 day s); and for those with goite rs , 20.9 days (S.D . = 17.6; ran ge 6- 91 days). T he resu lts indi cated GQ, VQ, and PQ were unrelated to treatment age for t he total CH sample, ,.(59) = 0.042, -0.135, and 0.061. For the etiological groups considered separately , none of the correlations was significant (p > 0.05) and there were no differences between the groups in their coeffic ients. Both th e ectopic and goiter groups demo ns t rat ed a slightly grea te r decrease in VQ than PQ with age, whereas

17

NEONATAL THYROID DEFICIENCY TABLE 4 Mean Griffiths Scale Scores 12 mo

Griffiths Scale

Athyrotic

Ectopic

=

(N = 7)

(N

Locomotor Personal-social Hearing and speech Eye-hand coordination Performance Reasoning

6)

24 mo

18 mo

Goiter (N

=

6)

Athyrotic

Ectopic

=

(N = 8)

(N

2)

Goiter

Athyrotic

=

(N = 2)

(N

92.5

116.5 116.5 102.5 105.;)

1:\7.9 l:l4.1 108.9 106.9

120.0

116.2

110.4

92.5 117.5

108.9 122.7

132.3 128.7

10:l.5 1:32.0

105.5 116.5

118.7 1:l:3.0

106.4

104.2

16 28 22 :3

88.0

TABLE G Percent of Subjects with Each Temperament Classification

Verbal

Performance

---------------

-----

111.8 121.1 109.4 109.3

13.7 13.3 17.5 15.6

Goiter

(N= 2) (N= 7)

114.5 119.5 106.0 103.5

Mean

AthyClassification

S.D.

- - - - - - - - - - - - - - - - - - - - - - - - - - - ---- - - - - - - - - - - -

Athyrotic Ectopic Goiter Hypoplastic

Ectopic

(N= 2)

134.3 1:n.7 121.3 104.3

96.0

S.D.

(N = :3)

7)

12:3.1 115.6 108.9 97.0

109.5 87.0

Mean

=

(N

At.hyrotic

129.0 110.0 94.5 96.5

111.3 100.2 106.2 108.2

--

Goiter

109.3 10G.5 110.0 107.8

121.8 112.2 112.9 109.0

N

Ectopic

108.0 101.6 102.8 111.0

106.0 110.2 114.2 101.7

TABLE 5 Mean Verbal and Performance IQs Across Groups Group

5)

:36 mo

101.3 103.7 109.1 97.3

10.5 11.0 9.5 7.0

Easy Difficult Slow-to-warm-up Intermediate-low Intermediate- high

athyrotics demonstrated a small positive effect. Thus, these results do not support Klein's (1980) claim that treatment age-IQ relations may differ according to etiology. Nevertheless these findings are still tentative and await further increment in sample size.

G9.2 0 7.8 23.0 0

:33.0 6.0 ILl 50.0 0

(N=

Hypoplastic

22)

(N=:J)

54.5

GG.7 0 0 0 :33.3

Goiter

9.0 1:1.6 1:1.6 9.1

Siblings (N = :39)

54.0 2.(j 8.G 22.(j 11.4

TABLE 7 Temperament Scale Scores of Congenital Hypothyroid (CH) Children and Siblings Sibling

CH

Temperament Unlike the IQ data, the temperament data were not examined according to test age, because there were no significant test age effects (Rovet et al., 1982) and because there was a high degree of test- retest reliability among subjects assessed more than once. Subjects providing more than one set of scores were assigned their mean score across assessments for each scale. The majority of CH children were considered "easy" by their parents. However, as shown in Table 6, this was more common for athyrotics than the ectopic or goiter groups. Hypothyroid children do not show any increased incidence of difficulty or of being slow-towarm up, nor do they differ from their siblings in any of the categories. Sibling Comparisons. The means for CH children

Ectopic

rot.ic (N= 18) (N= 16)

1. Activity

2. 3. 4. 5. G. 7. 8. 9.

Rhythmicity Approach Adaptability Intensity Mood Persistence Distractibility Threshold

Mean

S.D.

Mean

S.Il.

101.8 102.0 99.2 103.4 109.2 107.8 94.9 98.4 109.8

n.s 17.0 17.7 12.7 1:3.0 13.9 8.5 1:i.7 21.7

10:3.4 99.8 104.1 lOUi 106.5 10G.8 102.1 9G.5 J09.S

12.9 -0.57 22.:3 OAG 1:3.G --2.1 :3" O.G? 11.2 17.7 0.76 15.:3 0.29 11.8 --2.59" O.GO 11.:3 Hl.6 0

"» < 0.05. with goiter than the athyrotics, and a significant scale effect, F(8,496) = 3.38, p < 0.001, due to the low rhythmicity and high intensity and mood scores of the entire sample. The group X scale interaction, which was also significant, F(24,496) = 3.26, p < 0.001,

and matched siblings on the nine scales are provided

reflected the goiter groups lower ratings on the ap-

in Table 7. The results of matched comparison tests revealed that the CH children were seen by their parents as being more withdrawn in new situations and less persistent on tasks than their non-CH siblings. Etiological Comparisons. These data were analyzed by a 9 (scale) X 4 (group) analysis of covariance. A significant group effect was obtained, F(3,62) = 4.35, p < 0.01, due to the generally lower ratings of those

proach, persistence and threshold scales than the athyrotics' (Fig. 2). Thus, these results suggest that thyroid etiology appears to have a selective effect on temperamental characteristics.

Breast- versus Bottle-Feeding Cases breast-fed for at least 1 month were compared with those who were formula fed. Of those cases whose feeding status was known, 30 were breast-fed and :n

Ii')

ROVET ET AL. TABLE 8 Comparisons between Breast- and Bottle-Fed Congenital Hypothyroid Cases

110

Breast-Fed

Bottle-Fed

IQ Scale 1UO-

VQ

rr

PQ GQ

() ()

In D

~1~)

Mean

S.D.

Mean

S.D.

110.8 104.6 ]09.9

9.3 10.4 9.9

108.9 104.8 109.2

18.3 11.6 13.0

0.5] -0.07 0.21

-:..[ () U)

[:---1:

~ >

, u

'"

t

u

2

:r l,: C

ts:

.r U

-r

~ '"

I

TABLE 9 Partial Correlation Coefficients with Treatment Age for Breast-Fed and Bottle-Fed Cases

1(1!J1(

i; m

.(

h .(

>~

1-

Vi ,/

w

1-

L

U o(

o a :>

0

w

u

>

U

co

01::

L I~~

if; U)

0:: n

fCC U

;4

U)

CL

I I~

1U)

IQ Scale VQ

PQ GQ

Breast-Fed 0.076 -0.131 0.046

Bottle-Fed 0.595" 0.665" 0.650"

0

FIG.

2. Temperament scale scores by etiological group.

"» < 0.01.

bottle-fed. Comparisons of their VQ, PQ and GQ scores revealed that the groups did not differ on any scale. The results presented in Table 8 show that the two groups are remarkably similar. Breast-fed CH infants were treated at 17.0 days (S.D. = 7.9) on the average, whereas bottle-fed infants were treated at 2:3.8 days (S.D. = 28.2), t(59) = 0.23. Partial correlations (parent IQ and SES removed) were computed between VQ, PQ and GQ scores and treatment age. The results revealed that treatment delay was unrelated to IQ for breast-fed cases, whereas it correlated positively with IQ for bottle-fed cases

Of particular interest, however, is the finding of a subtle selective deficit in nonverbal skills for athyrotic, hypoplastic and ectopic CH children. This deficit, though minimal currently, may predict future difficulty in school-learning, particularly in subject areas requiring perceptual-spatial ability. We are currently attempting to diagnose this deficit more closely using a variety of diagnostic, perceptual, and cognitive tasks. Children with goiters did not display the same ability differential, obtaining equal scores in both verbal and nonverbal scales. The reason for this difference could be due to partial thyroid activity for those with goiters,

(TaLle 9). Thus, these results indicate that breast-

despite their dysfunctional thyroid glands.

feeding does not confer an advantage or protective benefit to the CH child; bottle-feeding, however, does appear to interact with treatment such that those treated later have the better results. This finding is certainly anomalous and warrants further investigation!

Although language skills were generally not depressed in the entire CH group combined, a deficiency was noted for those children tested at 36 months of age. This finding has also been observed by the groups from Quebec (Dussault et aI., 1982) and France (Rochiccioli et al., 1982), with some "catch-up" at the 4year age level (Rochiccioli et aI., 1982). Our preliminary results using the Reynell Developmental Language Scales (1977), however, fail to show that CH children are deficient in either expressive or comprehensive language skills (Rovet et aI., 1982). One possibilit.y is that this may be an artifact of the Griffiths test at 3 years of age and hence certainly warrants further investigation. A different pattern of results was also noted for the 18-month assessment than for the other test ages, which may reflect the greater behavioral instability among children at this age than at the other periods. It is interesting to note that Dussault et aI. (1980) have observed somewhat similar scale differences for this age group. Thus, concerning the intellectual consequences of CH, the major finding of this study is a selective deficit in the performance scale, which assesses perceptual-

Discussion The results of the present study indicate that ment.al retardation is being prevented by early detection and treatment of congenital hypothyroidism via neonatal screening. The CH children in the present study all had IQs within the normal range and, in fact, many had IQs above average, although below the levels of their siblings. (This may reflect inflated scores from out-dated norms rather than true superior ability, hence the value of siblings for control purposes.) An absent thyroid gland (athyrosis) appeared to be correlated with slightly lower IQ scores and a downward shift in the IQ distribution than was a goitrous, hypoplastic or ectopic gland. This finding therefore substantiates Klein's observation that levels of ability reflect amount of functioning thyroid tissue.

19

NEON ATAL THYROID DEFI CIEN CY

motor and spatia l abilities. This may reflect a disord er in t he normal p rocesses of right and left hemisphere specialization, due to less interhemispheric differen tia ti on or to a right hemi spher e dysfun ction . One possibili ty followin g Corba llis and Morgan (1978) is t ha t t hy roid hormon e deficien cy disrupts t he norm al developmental process in establi shing a left-r ight gra dient leading to left hemisphere dominance over right. This could resul t in decreased left hemi sphere spe cializat ion for lan guage processes, and consequently less right hemi sphere capacity for spatial skills (Levy, 1969), giving rise to difficulty in spa tia l functioning. This hyp othesis will be tested using tests of he mispheric lateral asymmetries once t he CH children are old enough to be assessed by our neur opsych ological in strument s. T he poorer locomot or sco res of CH cas es t han t hei r non-CH siblings is consistent with t he hyp othesis of ther e occurring slight cerebellar dam age from t hy roid hormon e ins ufficiency after birth (Morreale de Escobar a nd Escobar del Ray, 1980). As with ot he r disa bilit ies, t his effect is curre ntly bein g examined more closely using sen sitive tests of specific fine and gross motor abilities. Ability and delay of t reatment were essent ially un related when t he effects of parent IQ and SES on treatment age were rem oved from t he data. T he rela ti on ships did not differ for verbal an d nonverbal abiliti es as found by the MacFaul group (1978). The differ en ces bet ween t he different t hyroid groups were also only minimal. Thus t hes e result s do not suppo rt t he hypoth esis t hat t rea t ment age may inter act differen tly with intelligence depending on type of thyroid disorder. The tem pe rament test data indicate t hat CH chi ldr en are not more difficult t han norm al , as found for oth er handicapp ed groups (Black et a I., 1981; BrooksGu nn and Lewis, 1982). Their paren t s, however, see them as being more withdrawn in nov el sit uations and as pers isting less on ta sks. The signific ance of t hese characte ristics for t heir lat er learnin g will be examined when t hey are of school age. It is interesting to note that at hyrot ics were more favorably rat ed than wer e those with goiters, particularly on som e of the temp eram ent sca les. This could reflect sa mp ling bias, given t he small number of athyr oti c cases to dat e or, alternati vely, di fferen ti al t reatment or dosage effects on beh avior for t hese t wo conditions. That is, it is possible that the dosage or timing was mor e adequate for at hyrotics leading to a tempera menta lly easi er child. It is also in ter estin g to note t hat our preliminar y data showed better compliance, in t he sense of t ime for the hormone valu es to retu rn to norm al , for athyrotics than t he other groups (Ehrlich, 1982).

Finally, t he resul ts failed to show a protecti ve ben efit of br eas t -feedin g. Br east-fed and bottle-fed children obtained almost identical scores. The groups did differ , however, in t heir relati on sh ips between specific abilities and delay in t reat me nt . The meaning of t his differ ence is not clear at t he present t ime and awaits bot h an increme nt in sample size and more in tensive ability test ing of the two groups for clarification. In summary, t his st udy has shown t hat gene ral levels of ability are affect ed, but to a mini mal degree, by t hyroid hor mon e deficiency in utero and in t he early neonatal peri od, as indicated by comparisons with siblings. Moreover, there is some evidence for subtl e specific deficits t hat could give rise to later learning disahiliti es among these childre n. CH childr en demon st rated, in additi on, cha racteristic disposit ional te ndencies whic h could also interfere with the way they lea rn and interact with t heir en vironment . T he significance of these ten den cies will beco me par ticularly clear er in t he near future whe n t he neonatally screened CH children start to ente r school. T he resul ts of t he pres ent study indicate that t he effect s of t hyro id hormone deficiency are at tenuated to a significant degree when iden tificati on and treatment occur s ea rly in infancy . References AUBA SI, V. & ALDIGE. C. (1977), Eva luatio n of so d ium L-thyr o xine (T H) req uire ment in repl acem en t t he ra py of hypot hyr oi di sm . J.

Pediat., 90:298- :101. ANDERSEN, H . ,J. (197S), H yp ot hyroidism . In : En docrinology and Genetic Disease of Childhood, ed. L. I. Ga rdner. Phil a delph ia: W . B . Saun ders. ARNOLD, M . n., et al , (1981), E ffects of neonata l sc ree ni ng for hyp ot hyroid is m: pr eve nti o n of me ntal ret arda ti o n by t rea t ment hefor e man ifesta t io ns. Lan cet, 2: 109S- 1098. BALAZS, R., COCKS, W . A., E AYRS, ,J. T . & KOVACS, S . (1971), Bioch e mi ca l effects of th yroid hor mones on the developing hrai n . In : Hormones ill Deuelopmen i, ed . D . A. Ha m hurgh & K ,J. W . Ha rr in gt on . N ew York: Ap plet on -Ce nt ur y -Cro fts . BANGALl, R. C. (198 1), The in flu e nce of thy roxine ('1',) conce ntra t io n in human mi lk on neo na t al th yroid sc ree n ing . J . Pediatr. Res., 15:504. BENDA, C. E. (1941) , M ongolism and Cretinis m . 11 Study of th e

Clinical M an ifestations and the General Path ology of Pituitary an d T hy roid Deficiency. Lo ndon : H ein ema n . B LACK, F . W., G ASPARINI, B. & NELSON, R (1981), P a rental assess me nt of temp eram ent in ha nd ica pp ed chi ldr en . J . Pers. As s".,,,.. 4 h:1hh J hR. BHASEL, ,J. & B OYD , D . B . (1975) , In flu en ce of t hyroi d h orm one on fet al brain grow t h a nd developmen t. In : Perinatal Thyroid Pliysiology an d Disease, ed . D . A. F ishe r & G. N . Burro w. New Yor k: Ra ve n Press . B ROOKS-G UNN, ,J. & LEWIS, M. (1982), Tem perame nt a n d affective intera cti o n in ha ndicapped infants . P rese nte d a t. the Ha ndi ca pped C hild re n 's E arl y Ed uca tio n P rogra m Co n fere nce, Wash ing ton . BURROW, G . N. (198 0), In pa nel and gene ra l d iscuss io n: d iagn osis, t rea t me nt and follow up of c hi ld re n wit h co nge n ita l hypothyroidism . In : Ne on atal Thyro id S creeni ng, ed . G. N . Burrow & ,J. M. D ussau lt. New York: R aven Press .

20

IW VET ET AI,.

(1982), Ma t ern al -placental- fetal unit and t hyroid funct ion. P resen ted at. t.he Second Int ern a t iona l Confere nce on Neonata l T hyroid Scree nin g, T ok yo. - - & D USSAULT, J . M. (1980) , Neonata l Th y roid S creening, New York: Raven P ress. CAlIALA NE, S. F. & DOCKERAY, S . S. (1982), Confirma t ory pro cedures in diagno sis of prim ar y neon at.al hyp othyro idis m. P resented at. th e Second Inte rn at ional Confe re nce on Neo natal T hyroid Screening , T okyo. CAHEY , W . B. (1972), A s implified method for measuring in fan t t emperamen t. J . Ped iai., 77:188- 191. CAI{SON, D. •J., R OBEHTS, G., CAMPBELL, S . L. & CARSON, A.•J. (1982), Screen ing for congen ita l hypot hyr oidi s m in Northe rn Irela nd. P resent ed at t he Second In tern a t ional Confere nce on Neo natal T hyr oid Sc reeni ng, Tokyo . C m:EK, D. H. (197fi), T he fet us. In: Fetal and Postnatal Cellular Growth. H ormones an d Nutri tion, ed. D. B. Cheek . Ne w Yor k: W iley & So ns . ClIOI'I{A, l. ,J. (1972), A radioimm unoassay for measurem en t of th yroxine in unextracte d se I'll m. J . Clin. Endocrin. M etab., ;14 : !) ;~ 8 -94 !l.

COll EN, .J. (1977) , S tatistica l Poiocr Analysis for th e Behavioura l S ciences. New York : Academic Press. CONNELLY, ,I. F. (1982), Austra lian experi en ce in neon atal t hyro id scr een in g, 1!l77- J981. P resented at. the Second Intern atio nal Con terence on Neo nata l T hyroid Sc reeni ng, T okyo. CORBAL LlS, M. & MORGAN, M . (1978), On the biological basis of hu man lat.e ralit.y ; I. Evidenc e for a ma t ur ational left-ri gh t gra d ien t. Bcha u. Brain S ci., 2:2fil --;1:36. CIWME, L. & STEHN, ,J. ( I!ln ), !'atllOlugy of M ental Returdation. Ed inburgh: Church ill Livings tone. DELANCE, F. (I !l79), Neo nata l sc reening for congen it a l hypoth yroi dism in E ur ope. Report of the Newborn Com mittee of the Europeun T hyroid Associati on . A cta En docrin . Supp l., 223:90 . - - (1980), P a nel a nd genera l discuss ion: opti ma l sc reening a nd recall p rocedures, In: N eon atal T hyroid S creen ing, ed . G. N . Burrow & ,J. H . Dussault.. New York : Raven Press. - - (1982) , Iodi ne nut rition in p regnan cy a nd newborn thyroid function. P rese nt ed at t he Second In tern at ional Confere nce on Neon a tal T hy ro id Screening, T okyo . DlIONDT, ,I. L. (982), In te gra t ion of neonatal scree ni ng p rocedures- th e I"ren ch ex per ienc e, Pre sented at the S ucuud In tcru utio na l Co nfe rence on Neo natal T hy ro id Sc ree ning, T okyo. DOCKEHAY , S . S ., CAHALANI', S . F. , BIWDY , M ., M UL LINS, C. & CULLEN, M. J . (In80), Sc reeni ng for congenital hypot hyr oidism in t he rep ubli c o f Irela nd . Brit. Med. J ., 281:Jfi19- 1fi22. - -- O'M OOIU':, M . & CAHA LANI', S. F. (1982), Followup , psycho logica l and developm en ta l as ses sme nt s of infants det ected on neonatal scree ni ng. P resen ted at the Sec ond In tern ati onal Conference 0 11 Neon atal Thyroid Screeni n g, T okyo. DOBBIN!;, ,I. & SANDS, .1. (197:1), Quan ti tati ve growt h a nd devel opme nt of human bra in. Arch. V is. Child. , 48:7fi7- 7G7. DUSSAULT, ,J. H ., COU LO MBE, P., LABERGE, C. , LETAHTE, ,J., (; UYJ>A, H . & K HOURY, K. (H175), Prelim in ar y rep ort on a mass scr een in g program for neon a tal hypothyroidism . J. Ped iai., 8G:()70- G71. - - GLOHlEllX, .1., LETARTE, J . & GllYJ>A, H. (1978) , P reliminary report on psycho logical develop men t at age one of trea ted hypo thyroid infa nts det.ected in t he Quebec screen ing network for met a bolic disor der. ,J. Pe diat r. Res., 12:412. - -- LETAHTE , .J., G r.o nncux , ,J., MORRISSETTE, J. & LABERGE, C. ( 1980), P sych ological deve lop me nt of hypothy roid infant s at age J2 a nd 18 mon th s: ex pe rience a fte r neon ata l screen ing. In: Neo na tal T hy roid S creen ing, ed . G. N. Bur row & ,J. H . Dussault . Ne w York : Rav en P ress. - - Or.o uneu x , ,J., LETAnTE, ,J., GUYDA, H . & M o nlUs s ETTE, J . (1982), P relim ina ry result s on t he men t al developm ent of hypot hyroi d in fan ts det ected by t he Quebec sc reen ing progra m. P rese nte d at t he Se cond In te rn at ional Confe rence on Neona tal T hyro id Sc ree ni ng, Tokyo . EAYHS, .J. T. (19iiG), T he ce reb ra l cortex of norm al and hypothy roid ra t s. Acta A na i., 2fi:l fiO- 18il.

-

- (19GO), In fluenc e of I.he th yro id on the cent ral nervous syst em. Br it. M ed. nuu; 16:122-J 27. - - (19fi6), T hyroid an d central nervo us developm en t. In: The Sc ientific Hoses of M edicine and A n nua l Reviews. London : At hlone P ress. -- - (1971), T hyroid a nd developing brain anat omical and beh avioural effects . In: Hormones in Developm ent, ed. D. A. Ha mbur gh & E. .J. W. Ba rrin gt on . New York: App let on -Cen tury-Crofts. E HRLICH, It. (1982), Present ed at t he Endocri ne Group Meet ing, Mou nt Si na i Hosp it a l, T or on t o. E RMANS, A. M " BOUDOUX, P., LAGASSE, R., DELAN GE, F. & T IIILLY, C. (1980) , Congen it al hypothyr oidism in deve loping cou ntries. In : N eonatal Thyroid Screeni ng, ed. G. N . Burrow & J . H . Du ssault. New York : Raven P ress. FARRIA UX , J . P . & DHONDT, ,I. L. (1982), Resu lt s of a follow-up p rocedure for conge ni ta l hyp othyr oidism . P resen t ed at t he Secon d Int ernational Co nfere nce on N eon at al T hyroid Screen in g, To kyo. FISHER, D. A. (1975), Thyroid fun cti on in t he fetu s. In: Perin atal T hy roid Physiology and Disease, ed. D. A. Fisher & G. N . Burrow. New Yor k: Raven P ress. - - (1980), H ypothyr oidism in chil dh ood. Pedia t. Rev., 2:67-74. - - (1982), T hyroid func t ion in t he p rem atur e infant . P resen ted at th e Seco nd In t ernat ion a l Confe re nce on Neon atal T hyroid Screen ing , T ok yo. FULLA RD W ., MCDEVITT, S . & CAnEY, W . (1983), Asse ssmen t of te mpera men t in one to t h ree year old chi ld ren. J . Pediat. PsychoI. (in pr ess). GARRON, D. (1977), Int.elli gence a mo ng person s wit h T urn er's sy ndrom e. Beha o. Genet., 7:10fi-127. GESELL, A., AMATRUDA, C. S . & CULOTTA, C. S. (1936), gffect of t hyroid t hera py on t he menta l and p hysica l growt h of cret inous infants . A rneI'. J. Dis. Child., 5 0 : 111 7 - U;~8 . GHIFFITHS, R. (1954), T he Ab ilities of B abies. London : Un iversity of London P ress. - - (1970) , T he Abilities of Young Children. Cha rd , So me rset: You ng & So n. H ALL, R & SCAN LON, M . R. (1979) , H ypothyr oidism, cli n ical features and complications. In: Clinics in Endocrinology and M etabolism, Vol. 8, No. 1, ed. D. Evered & R. Hal l. London: Sa unders. H AMBUR(; II, M. & FLEXNER, L. B. (19fJ7), Biochemi cal and p hysio lo g ic u l d i f'l'c rc n t.iu t .io n d uri n g morp h o g o n os is . Effec t.s of h y p o -

th yr oid ism an d hormone therapy on en zym e ac t ivit ies of t he cerebral cortex of t he rat. J . Neurochem., 1:279- 288 . - - M ENDOZA, L. A., BURKAHT, J . F . & Wrerr., F . (1971), T hy roiddepend en t p rocesses in t he develop ing ner vous sys t em. In: Hormon es in Develop ment, ed. D. A. Ha mb ur gh & E . •J. W . Har ringto n. New York : App leton-Century -Crofts, H EGVIK, R. L ., McD EVITT, S . C. & C A R~:Y, W . B. (1981), The assessment of te mperamental ch aracteristics in eight- t o tw elveyear-old ch ildre n. P resented at t he So ciet y for Resea rch in Ch ild Development mee t ing, Boston. H INES, M . (1982), P ren at a l gona dal hormon es and sex differe nces in hu ma n beh aviour. Psyc hol. Bull., 92:56-80. H OLLIN GSHEA D, A. & HEDLlCH, F. C. (1958) , Soc ial Class and M ental Illness. A Com mun ity Study . N ew York : Wile y. HOLT, A. B., K ERR, G. R. & CHEEK, D. B . (1975), Prenat a l hypoth yroidism a nd brai n composit ion . In: Fetal and Post-natal Cellular Growth. Horm ones and Nutrition, cd. D. B. Cheek. New York : .loh n W iley & Sons . H ULSE, ,J. A., GHANT, D . B., J ACKS ON, D. & Cl.AYTON, B . E . (1980), P opul a ti on screen ing for congen ita l hypot hyro idis m. Brit. M ed. J. ,280:fi7fi-678. II.L1 G, R. (1979), Con gen ital hyp ot hy roidism. In: Clinics in Endocrinology and M etabolism , Vol. 81, No . 1, ed . D. Eve red & R. Hal l. London: Sau nders. IRIE, M . (1980) , Sum ma ry of ne wbo rn thyroid screen in g.•Japanese experienc e. In : Ne onatal Thyroid Sc reening, ed. G. N . Bu rrow & .1. H. Du ssau lt. New York: Raven P ress. ,JOlIN, R. & W OODH EAD, ,J. S . (1982) , An a ut omated im munoradi SUTIIEJ{LAN D, H. M., HATCLIFFE, ,J. G., J ACKSON, H . ,J., F F.IWUSONSMITH, M. A., KENNEDY, It & GmDWOOD, It W . (1982), I{ela -

NEO N AT AL TH YROID D E F ICIEN CY ometric assay of thyrotroph in in dried blood filte r pa pe r spo ts . P resented at t he Second In te rn a t ional Confe re nce on Neonata l T hy ro id S cree ni n g, T o kyo. KAPLAN , S. L. (l 9HO), In pa nel a nd gen eral d iscussion: dia gnosis, treatment a nd foll owu p of children wit h con ge n ital hyp ot hy ro id ism. In : N eonatal Thyroid S creeni ng, ed . G. N . Burrow & J . H . D ussa ul t. New Yor k : Ra ve n Press . KE NNY, F ., KLE IN, A., AUGUSTIN, A. & FO LEY, T . (19 75), Sp or a d ic c ret in ism. In : Perinatal Thyro id Phys iololJY and Disease, ed, D . A. Fi s her & G . N . Burro w. New York: Ra ven Pres s. KLEIN, A. , M ELTZER, S. & KE NNY, F . M . (197 2) , Imp roved p rognosis in con gen it a l hypoth yroid ism t re ated before age t hree mo n ths . J . Ped iat., 81:812- 915. K LEIN, R . Z. (1979) , Neonatal sc ree n ing for hypot h yr o idis m. Adv.

Pediat., 26:4 17-·440. -

- (198D), H istory of congen it a l h yp ot hyr oid ism . In : Neonatal T hy roid S creen ing, ed . G. N. Burrow & ,J. H . D ussa ult. N ew York:

Rave n P ress . KLETT, M ., SClI ONllEIW, D ., HOIINERT, R & WI LLE, L . (1982), In flue nce o f va rious cl inical co n d itions o n thyroid functi on in t he newborn . P rese n ted at the Se cond In te rn a t ion a l Con fer ence on Neonata l T hyroid Screen in g, T ok yo. KOCHUPILLAI, N. , GOAIlOLE, M . M ., KARlIIAHKP.R , M . G., DANOAV , C. S., VASUKI, K & A IIU,IA, M . M . S . (1982), T S H, T " '1'3, a nd r'I', in cord bloo d of ne wbo rns from a reas of d iffer in g en dem icit y for goit re. P re sen ted at the Secon d Intern a tion al Con ference on Neonata l Thyro id Screen in g, T ok yo. LAFHANCIII, S . H . (1980 ), Newborn sc ree n in g for co ngen ital hypot hy ro idism . Pediat. Ann., 9/ 10:390- 398. - - M URPIIEY, W . H ., F OLEY, T . P ., LARSEN, P . R & B UIST, N . R (1979), Neo nata l hy po t h yr oidis m detected by the northwest regio nal sc reen ing progra m. Pediatrics, 63:180- 191. LAHsE N, P . R. & B IWSKIN, K . (19 75) , Thy roxine im munoa ssay usin g ca p illary bl ood samp les collec te d on filte r p aper. In : Perinatal Th y roid Phy siology and Dis ease, ed . D . A. Fi s her & G. N . B u r row . N ew York: R av en P ress. LAHSSON, A., L.IUNGGHEN, J ., E KMAN, K , N ILSSON, A., O LIN, P . & BODEGAltD, G . (l981), Sc reening fo r co n ge ni ta l hypot hy ro id ism. II. C lin ica l find ing s in in fa n ts wit h pos it ive scree ni ng tes ts .

A cta Paediai. Sca nd., 70:147- 153. LAYD E, P . M ., VANALI.MEN, S. D . & OAKLEY, G. P . (19 79) , Con ge nital h yp othyr o id ism co ntrol p rograms. A cost -be ne fi t a na lyis,

J. A rneI'. M ed. Ass n. , 241:2290-2292. LETARTE, ,J., G UYOA, H. & DUSSAULT, ,J. H. (1980), Clini ca l bio che m ica l and radiological fe at ur es of neon a tal hypothy roid in fan ts. In : N eonatal Thyroid Screening, ed. G. N . Bur row & ,J. H. Du ssault. N ew Yo rk : Raven P ress. L EVY, J . (19 69) , P ossible ba si s fo r the evo lu ti on of latera l spe c ia li za t ion of t h e h u m a n brain . N atur e, 224:6 15. L ISTEH, C. M . (19 79), E arly dev e lopmenta l ass essm e n t to me et p ra ct ica l needs . Acta Paedopsy chiat., 45:219-223. MACCOBY, E. K & J ACKJ.lN, C . N. (1974) , T he Psychology of Se x Diffe rences. Stanford , Ca lif.: Sta n ford U ni versit y Press. MACF AUL, R, DORNEH, S ., BHETT, Eo M. & GRANT, D . B. (1978), Ne urolog ical a b no rm a lities in pa t ien ts treated for hypoth y roidism from early life. A rch. Dis. Chi ld., 5:l:6 11- 6 19. MAENPAA, J . (1972), Co nge n ital hypothyr o id ism-aetiologic al a nd cl inical as pects. Arch. Dis. Child., 47:914·-923. MATHUR, K. S ., CONNELLY, ,J. , G OLD, H ., DUGOALE, L . M ., ANORI';WS, ,I. T . ,~ I.l cII TENs Tm N, M . ( 198 2) , Va llie of 99", 1'<: sca n ni n g in co nge n ita l hypot hy ro id is m ba se d o n five yea rs e xpe rience. Present ed a t t he Secon d Intern at iona l Conference on N eo n atal T hy roid S cre e n in g, T ok yo. M cDEV ITT, S. & C AHEY, W . (1978 ), T he m easurement of tem p er ament in :\..·7-yea l'-0Id c h ild re n . J . Child Psychol. Psych iai., 19:24525:l. M EIJEH, "V. J . (19H2), Ev a luation of one-year na t ion -wide scre en ing fo r CHT in the Nethe rl a nds . Presen te d at t he Second Interna t iona l Co nfe rence on Neonatal T hyroid Scree n ing, Tokyo. M ITCHELL, M . 1.., LAHSEN, P . R , L EVY, H ., BE NNETT, A. J . E. &. MADOFI' , M . A. (1978) , Scree n in g for congen it al hypot hy roid ism:

21

result s in t he newborn po pu la tion of New Engla nd. J . A rneI'. M ed.

As sn ., 239 :2348 - 2351. M ITSKEVICH, M . S . & MOSKOVK IN, G . N . (1971) , Som e effects of thy roid hor m one on t he develop m e n t of t he ce n t ra l nervous sys tem in early on t oge ne sis. In : Hormones in Developm ent, ed . D. A. Harnbu rgh &. E. ,J. W . Ba r ri ngto n. N ew Yo rk: Ap ple ton Ce n t u ry-Crofts. MON EY, ,J. (195 6), P sy chologic st ud ies in h ypot hy roi di s m . A rch. N eu ral. Psychia t., 76:296--:l 09. M OHHEA LE 0[>: E SCORAH, G. &. ESCOBAI( DEI. REY, F. ( 1880), B rai n da m a ge a nd t hyroid hor mone. In : Ne ona tal T hyroid Screenin g, ed. G. N . Burro w. New Yo rk : Raven Press. - - P ERALES, M . C ., M ONTIEl., F., PASTOR, R, AHANDA, A., OHREGON, M . J . & E SCOBAR DEI. REY, F . (19 82) , Neonata l t hy roid sc ree n in g in two a re as of Spain . P resen ted a t the Second In t e rn ational Conferen ce on N eo natal Thy roid Scr een in g, Tokyo. MYANT, N . R. (1971 ), T he r ole of thyro id h orm one in t he fetal and po st na t al de velop m ent of m a mm a ls . I n : Horm ones in Develop me nt, ed. D. A. I-lamburgh & E. ,1. W . Ha rrington . New York:

Appleton -Century-C rofts. N AHUSE, H ., ISHII, S ., M OMOSE, '1'., KATO, N ., Ts u,JI, A., AHAKAWA , H ., S HIRANE, H ., IRlE, M ., KUN ITA, N ., T AKAS1H;J, N . & K LEINIIAMMEH, G . (1982), Neonata l t hyroid sc ree ni ng with e n zy me im munoassay. P rese n ted at t he Seco nd In te rn a t io na l Co n fe ren ce on Neonatal Thyr oi d Scree ning, T okyo. OBERKOTTER, I.. V., TE NORA , A., KOI. DOVSKY, O. & PARIS, ,1. S . (19 8 1), Se pa ratio n a n d ra d io- im m unoassay of trii od othyro nin e (T ,) in h u m a n brea st mi lk . J . Ped iatr. Res., 15:512. PRI CE, D. A., E IIHJ.lCII, R . M . & WALFISH, P . G. (198 1), C onge n ital hypot hyroidis m: clinical a nd la bo ratory cha ra cte ri stics in in fa nts det ected by neon ata l screen ing. Arch. Dis. Child. , 56:84G-B5 1. RAMSAY, M . & FIT7. IlAHDINGE, P . M . (19 77) , A comparative st udy of tw o deve lopmen ta l scales : t he Bay ley a nd t.he Gri ffit hs . Early H um . Devel., 1/ 2:1Gl --157. I{EDMOND, G. P. (1982 ), T hera py of co n gen it al hypoth yroidis m in the era of ma ss scr ee n in g. S em . Pc rin at., ():181 -189. HEED, H. & LAVECCllIO, F. (1980) , In pan e l a nd ge neral d iscu ssi on : d ia gnosis, t rea tme nt a nd follow up o f c h ild re n wit h co nge n ita l hypothyr oid ism. In: Neonatal Thyroid S creeni ng, cd . G. N . Bu r row & J . H . D ussa ult. N ew Yo rk : Ha ven P ress. R EYNELL, ,1. K. (1977) , Th e Reyn ell Developmental Lan guan« Sca les (revised) . Wi nd sor, E ng la nd: N F E R Pu blishing Co m pa ny . REZVANI, I. & D IGIWH GE, A. M . (1977 ), R eassess m en t of th e dai ly do se of ora l thy ro xin e fo r re p la ce me nt therapy in hypot hyroid childre n . Ped iatrics, 90:291-2 97. ROllE HTSON, E. F ., O LlWIELD, It, WIL KINS, A. , P OLl.AHD , A. & GUERIN, M . (197H), Sc ree n in g of newborn in fa n ts for hy pothy roi d ism . k led. J . Austral ., 1 / I :H)9 ~1 -59 G . ROCIIICCIOLI, P . (19HO), In p a ne l an d gene ra l di scu ss ion : d iagnosis, t rea tm e nt. a n d foll ow up of c h ildren with congen ital hypot h y ro id is m. In : N eona tal T hy roid S creen ing, ed . G. N. Bu r row & ,J. 1-1 . Du ssaul t. New Yo rk : Ra ven P ress . - - ROGE, B., ALEXAN ORE, F . & D UTAU, C; . (19 82), A st udy o n sem at ic a n d en v iron m ent factor s of p syc homotor development in 35 hypot hyr oid ia ns sc reen ed . P resented a t t he Sec ond In t e rn atio na l Con fere nce on Neona tal Thy ro id Sc ree n ing , Tokyo . ROVET, J . F., E IIHLlCH, R , W ESTHIWOK, D . & W AI.FISII, 1'. (lH 82) 1 In t ellect ua l and behavioural asses s m en t of ch ild re n with con ge n ita l hypothyroid is m ascertained throug h neonatal sc ree n in g: Th e ' To rcmto P n ls p e d ivo St.ud y . Pre s c n t.cd a t t.hc S e c o nd

{r tt e rn n -

ti ona! Co n fe re nce on Neonata l Thy roi d Scree n in g, T okyo. SACK, .I. , FRUCHT, 1-1 ., AMADEO, 0 ., HHISII, M. & L UNENFEI.Il, B . (19 79), Breast m ilk thyro xine a n d no t cow's milk m ay miti gat e a nd de lay t.he cl in ica l p ictu re of n eona ta l hypoth y roid ism . A cta Paediatr. Sca nd . Suppl. 277:54- 56. S HEPAHIl, T. H. (1971 ), Devel op men t o f t he h uman fe tal thyr o id . In : Hormones in Develop ment, ed . D . A. H a rn bu rgh &. E. ,1. W . Ba rr in gt on . N ew York : Appleton-Cent ur y -Crofts . S MITH, D. W ., BLI ZZAIW , R M . & W ILKINS, L. (lH 5 7), The me n tal p rog no sis in hypot hy roi d is m o f infancy a nd c h ild ho od . Pediatrics, 19:1 0 1 1-·1022.

22

ROVET ET AL.

t ions hip of th yroid fun cti on test s to aetiology in neon ates with primar y hypothyr oid ism detected by dried blood spot TSH . Presente d a t the Sec ond Intern ational Confere nce on N eonat al Thy ro id Scr een ing, T okyo . TIIERRI';U " B. r•. (HlH2), Computerizati on in th e newborn scree ning la borat ory: a n aid to da ta ma nagem en t. Present ed at t he Sec ond Int e rn ati ona l Con fere nce on Neonat al Thyro id Scree n ing, T okyo. TII IEn-HEY, A. F., DIIONIlT, ,I. 1.., FAltRIAUX, ,I. P . & PARQUET, P. I !. ( 1 DH2), P sycho logical cost of neona tal sc reen in g t o fam ilies. Prcsented at the Second In ternational Conference on Neo nat al Th yroid Sc reening, T okyo . T IIOM AS, A. & e IlESS, S . (1977), Temperam ent and Development . New Yor k: Hrun ner/Mazel. T IIOIm s , O. A., J ENNER, M. R., MACM ILLAN, A. B. , BOLTON, R. ,I., HOWAIW, N . ,J. & ALEXAN DEH, D. S . (1979), H ypot hyroid ism screen ing: 11 cas es in 6 months. On to Med . Reo., 46/ 6:273 . VANDEHSH UEHAN -LOIlEWEYCKX, M ., MALVAUX, P ., CRAEN, M ., E ltNOULll , C. & WOLTER, R. (1980 ), N eur opsyc hologica l st udy of tr eat ed ch ild ren with th yroid dysgen esis: Experience before t hyroid screeni ng . In : N evnatal T hy roid S creeni ng, ed. G. N . Burrow & ,1. H . Dussau lt. New Yor k: Raven Press. WAI.FISII, 1'. G. (1975), Screen ing for neon atal hypot hyro id ism

usin g a dried capilla ry blood method: observ at ion on me t hodologic factors, select ion criteria and pr eliminar y resu lt s. In: Perina tal T hyroid Physi ology and Disease, cd. D. A. Fis her & G. N. Burrow. New York: Raven Press. - - GINSBERG , ,J., ROSENBEltG , R. A. & H OWARD, N. J . (1979), Resu lt s of a regional cord blood screen ing program me for det ectin g neo nata l hyp othyr oidism . A rch. Dis. Child., 54:1-7 . - - GERA, E. & EHRLICH, R. M . (198 2), Primary TSH scree n ing for neonatal hypothyroidi sm : Results of simulta neous cor d and neon at al heel blood T SH testin g wit h in t he same in fant populat ion. P resented at t he Second Int ern at ional Conference on Ne ona tal Thyroid Scree n ing, Tokyo. WECHSLER, D. (198 1), Wechsler Adult I ntelligence S cale. New Yor k: Psychol, Cor p. WECIISLER, D. (1967 ), Wechsler Preschool and Prima ry S cale of Intell igence. New York: Psycho!. Corp. WECHSLEH, D. (1974), Wechsler Intelligence Sc ale for ChildrenRevised. New York: P sychol , Corp . WOLTER, R , NOEL, P. , DECOCK, P ., CHAEN , M., ENOULD, C. H ., MALVA UX, P. , VERSTRAETA N, F. , SIMONS, J ., MERTANS, S. & VAN BHOICCK, N. (1979 ), Ne ur opsycho logica l st udy in t reat ed t hyroid disea ses. Acta I'aediat . S cand . Suppl. 227:4 1- 46.