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Medycyna Wieku Rozwojowego, 2012, XVI, 3© IMiD, Wydawnictwo Aluna

Wlodek Lopaczynski , MD, PhDNational Institutes of Health, Bethesda, Maryland, USA

Abstract

Recently, scientific literature informed that metabolic conditions in pregnant women may be associated with increased risk

for autism and other neurodevelopmental disorders in their offspring. In a cohort study of more than 1000 children between

the ages of 2 and 5 years, those who had mothers classified as having "metabolic conditions" (which included diabetes,

hypertension, and obesity) during pregnancy were at a significantly higher risk for developing an autism spectrum disorder(ASD) and neurodevelopmental delays. In addition, mothers with obesity were 1.6 times more likely to have a child with ASD

and more than twice as likely to have a child with other developmental problems. In the United States, the prevalence of

obesity among women of childbearing age is 34%. Moreover, with obesity rates rising steadily, these results appear to raise

serious public health implications. The main objective of this Editorial is to propagate the health care improvement based on

the translation research approach from basic behavioral sciences and relevant integrative neuroscience to pressing clinical

issues that include an understanding of the etiology and assessment of disorders, and the assessment of functioning and de-

velopment of innovative and culturally appropriate preventive treatment. Behavioral interventions for weight management

in pregnancy may include the Transtheoretical Model (TTM) employed in obese pregnant women and then, the comparison

with elements of the ecological model. A comparative effectiveness design is to test the effect of tailoring while including one

of the most important predictors of screening-physician recommendation: after careful selection of analyzed behaviors from

the TTM approach. However, there is also a risk that the evidence may not be conclusive for sustained weigh loss as a primary

outcome of the proposed intervention, although the TTM in combination of physical activity and diet tended to produce sig-nificant results. Therefore, physicians might use the TTM to convince pregnant women to regulate weight and educate future

 parents on how to deal with autism at an early age of their children using watchful waiting management.

e increasing importance of translational researchby applying specific approaches in order to improvehuman health and well-being is helping to bridge thegaps among science, policy and practice. In general,translational research refers to the “bench-to-bedside”

enterprise of harnessing knowledge from basic scienceto produce new drugs, devices, and intervention optionsfor patients. For this area of research, the end pointis the production of a promising new treatment thatcan be clinically used. However, for others, especiallyhealth services and public health researchers whosestudies focus on health care and health as the primaryoutcome, the translational research refers to translatingscience into practice by ensuring that new interventionsor treatments and research knowledge actually reachpopulations for whom they are intended and adequatelyimplemented. e purpose of this Editorial is to propagate

the translation of work from basic behavioral science

and relevant integrative neuroscience research by press-ing issues regarding some aspects of clinical disorders,including: an understanding of the etiology and assess-ment of disorders; the assessment of functioning; thedevelopment of innovative and culturally appropriate

preventive treatment and rehabilitation interventions;and improvement of methods for the effective deliveryof public health services. I also intended to encouragebehavioral scientists to seek further understanding ofbehavioral processes through an exploration of how thoseprocesses are altered by mental and behavioral disordersto transcend the barriers of disciplines in research andinstitution settings in order to harness the full range ofmodern behavioral sciences to service of the criticalhealth needs. For this purpose, I will summarize brieflysome recent studies related to this topic.

Historically, improving the dietary health of nationsthat are fighting obesity has been a long-standing goal

Wlodek L aczynski , MD, PhDNational Institutes of Health, Bethes a, Marylan , USA

Abstract

Recently, scientific literature in ormed that metabolic conditions in pregnant women may be associated with increased risk

or autism and other neurodevelopmental disorders in their offspring. In a cohort study o more than 1000 children between

the ages o 2 and 5 years, those who had mothers classified as having "metabolic conditions" (which included diabetes,

 ypertens on, an o es ty ur ng pregnancy were at a s gn cant y g er r s or eve op ng an aut sm spectrum sor er(ASD) and neurodevelopmental delays. In addition, mothers with obesity were 1.6 times more likely to have a child with ASD

and more than twice as likely to have a child with other developmental problems. In the United States, the prevalence o

obesity among women o childbearing age is 34%. Moreover, with obesity rates rising steadily, these results appear to raise

serious public health implications. The main objective o this Editorial is to propagate the health care improvement based on

the translation research approach rom basic behavioral sciences and relevant integrative neuroscience to pressing clinical

issues that include an understanding o the etiology and assessment o disorders, and the assessment o unctioning and de

velopment o innovative and culturally appropriate preventive treatment. Behavioral interventions or weight management

in pregnancy may include the Transtheoretical Model (TTM) employed in obese pregnant women and then, the comparison

with elements o the ecological model. A comparative effectiveness design is to test the effect o tailoring while including one

o the most important predictors o screening-physician recommendation: a ter care ul selection o analyzed behaviors rom

the TTM approach. However, there is also a risk that the evidence may not be conclusive or sustained weigh loss as a primary

outcome o the proposed intervention, although the TTM in combination o physical activity and diet tended to produce significant results. There ore, physicians might use the TTM to convince pregnant women to regulate weight and educate uture

 parents on how to deal with autism at an early age o their children using watch ul waiting management.

e increasing importance of translational researchby applying specific approaches in or er to improve

uman ea t an we - e ng s e p ng to r ge t egaps among science, policy an practice. In general,translational research refers to the bench-to-be si e

enterprise of harnessing knowle ge from basic scienceto pro uce new rugs, evices, an intervention optionsfor patients. For this area of research, the en pointis the pro uction of a promising new treatment thatcan be clinically use . However, for others, especiallyhealth services an public health researchers whosestu ies focus on health care an health as the primaryoutcome, the translational research refers to translatingscience into practice by ensuring that new interventionsor treatments an research knowle ge actually reachpopulations for whom they are inten e an a equatelyimplemente . e purpose of this E itorial is to propagate

the translation of work from basic behavioral science

an relevant integrative neuroscience research by pressing issues regar ing some aspects of clinical isor ers,nc u ng: an un erstan ng o t e et o ogy an assess

ment of isor ers; the assessment of functioning; theevelopment of innovative an culturally appropriate

preventive treatment an rehabilitation interventions;an improvement of metho s for the effective eliveryof public health services. I also inten e to encouragebehavioral scientists to seek further un erstan ing ofbehavioral processes through an exploration of how thoseprocesses are altere by mental an behavioral isor ersto transcen the barriers of isciplines in research aninstitution settings in or er to harness the full range ofmo ern behavioral sciences to service of the criticalhealth nee s. For this purpose, I will summarize brieflysome recent stu ies relate to this topic.

Historically, improving the ietary health of nationsthat are fighting obesity has been a long-stan ing goal

*is article was prepared by Dr. Lopaczynski in his personal capacity. e opinions expressed in this article are the author's own and donot reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.

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of healthcare researchers and practitioners, as well asmany governments. For example, in the United Statesof America (U.S.), about half of women of reproduc-tive age are either overweight, or obese. Additionally,according to the American Pregnancy Association,there are approximately 6 million pregnancies every

year throughout the U.S. Although most obese womenwill have a good overall obstetric outcome, obesity hasbeen a major predictor of maternal mortality and hasresulted in major complications according to recentstudies (1). Major complications associated with obe-sity include: subfertility, fetal macrosomia, hypertensivedisorders of pregnancy, prolonged labor, gestationaldiabetes, Cesarean birth and associated anesthetic andsurgical complications, congenital malformations, andfirst trimester spontaneous abortion. Recently, scientificliterature informed that metabolic conditions in obese

pregnant women may be associated with increased riskfor autism and other neurodevelopmental disorders intheir offspring. In a cohort study of over 1000 childrenbetween the ages of 2 and 5 years, those who had moth-ers classified as having "metabolic conditions" (whichincluded diabetes, hypertension, and obesity) duringpregnancy were at a significantly higher risk of developingan autism spectrum disorder (ASD) and neurodevel-opmental delays than the children with mothers whodid not have metabolic conditions. Also, mothers whowere obese were 1.6 times more likely to have a childwith ASDs and more than twice as likely to have a child

with other developmental problems (2). However, nostatistically significant associations were found betweenovert diabetes and ASD, or between hypertension andASD or developmental delays.

For a significant time, the Transtheoretical Model(TTM) stages of change have been considered a usefulinterventional approach in lifestyle modification programs,including weight loss management for overweight andobese adults (3). Also, mastering behaviors related tonutrition, physical activity and weight management arethe main issues in obese pregnant women. us, these

approaches can be also recommended for both efficacy andcost-effectiveness, and TTM intervention can be tailoredto test the needs of individuals while treating the entirepopulation of pregnant women with obesity. Before theintervention, associations have to be assessed betweenmeasures used by health care services and Body MassIndex (BMI, defined as the weight in kilograms dividedby the square of the height in meters), to categorize thepregnant women as underweight (BMI30.0). Finally, the intervention using theTTM approach can provide a foundation for the de-

 velopment of more effective behavioral interventionsutilizing the social ecological model.

Briefly, obesity is a global public health issue and theTTM model for dietary and physical exercise modification

in weight loss management for overweight and obeseadults has been oen useful; however, its effectivenessin producing sustainable weight loss in such individualshas been found to vary considerably (3). Although TTMmay apply across at least 48 behaviors and populationsfrom many countries, the model still has some general

limitations (4). In addition, decisional balance (4), whichreflects an individual pregnant woman with obesity,the pros and cons of changing, are also expected to beobserved during this intervention. However, there isconcern about self-efficacy, including confidence, andthere is also a high risk that there can be no conclusiveevidence for sustained weight loss as a primary outcomeof the proposed intervention (3). Nonetheless, the TTMmay be especially useful in developing healthy behaviorfor pregnant women with obesity, as well as - at the sametime - physicians might use the TTM to convince pregnant

women to regulate weight and educate future parents onhow to deal with autism at an early age (2-5 years) of theirchildren. is TTM approach can be applied in manysettings, including primary care, obstetric/gynecologi-cal offices, homes, churches, and some communities orworksites. In addition, the initial intervention using theTTM approach can provide background for the develop-ment of more specific approaches utilizing the ecologicalmodel, including the intervention that is designed aercareful selection of one most promising behavior froma tailored intervention. Particularly, pregnant womenwith BMI >30 should be selected for this intervention.

Recent studies from a British research group (5) claimthat despite intense and oen tailored behavioral inter-

 ventions for weight management in pregnancy, there isno statistically significant healthy management reportedin qualitative studies, which was addressed so far in theinterventions, but this in itself was insufficient to leadto reduce weight in pregnant obese women. erefore,potential interventions should be focused on these womento address the impact of changes in incentives for BMIreduction during pregnancy.

On the other hand, while there is much hope and

anticipation in the ASD professional and parent com-munities, which increased public awareness, currentlymany barriers to early and appropriate diagnosis andtreatment still remain (6). Importantly, distinguishingbetween cognitive or language delays and social com-munication delays in ASD may be subtle and not easilyrecognized. However, parents can be the best resourcefor identifying young children whose development andbehavior appear atypical. Also, parents who bring con-cerns to a pediatrician have been shown to be the primarycause of identification of many medical and behavioralconditions diagnosed at health supervision visits (7).

e need for parental input, particularly regarding thediagnosis of ASDs, has been impressively illustrated inbooks for and by parents of children with ASDs (6, 8).ese books and other media are likely to improve par-

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ents' knowledge and observational skills. is increasedawareness should improve identification of aberrationsin typical development and behavior to advance earlyidentification of ASD. us, the final step in identifyingASD may include watchful waiting (also called: watchand wait, expectant management, or active surveillance

(9) ), which needs to be applied to the entire study cohortin a pediatric/family practice office as a recommendedapproach to diagnose ASD in children with a medicalproblem related to obesity during the mother’s pregnancy.Obviously, during that time, repeated testing for ASD mustbe only performed by qualified medical personnel. iskind of intervention builds on prior research, includingstudies that demonstrate the advantage of tailored inter- ventions as compared to generic or targeted designs (10).

In the time of ever-expanding knowledge about andintense focus on autism, there is a major concern on

how pediatricians should respond to parental concerns.ough pediatricians may not always have the answers,they will not go wrong if they listen to parents and ac-knowledge their concerns. e message "wait and see"is understandably a battle cry to parents who worry thattheir children have true delays. Children with atypicalsocial/emotional development as toddlers may ultimatelybe diagnosed with ASD, a language disorder, cognitivedelay, sensory integration dysfunction, attention-deficit/hyperactivity disorder, or merely a challenging tempera-ment by the time they are school aged. In the face ofparental concern, the critical issue for pediatricians is to

distinguish children with a problem requiring an immedi-ate, intensive intervention from one for whom watchfulwaiting is appropriate. Additionally, a key component ofwatchful waiting is the use of an explicit decision treeor other protocols to ensure a timely transition fromwatchful waiting to another form of management, asneeded. is is particularly common in postsurgicalmanagement of cancer survivors, in whom cancer re-currence is a significant concern.

Although there was a relationship between obesityand autism, the concept itself is obviously controversial

since there was also a very modest association foundbetween the developmental disorders and diabetes(2). For example, Dr. Max Wiznitzer, who is also theneurology liaison to the Autism Subcommittee for theAmerican Academy of Pediatrics, recently stated that thereal question is about the interpretation of Krakowiak’sresults (CNN Health, April, 2012). For example, obesewomen have an increased risk for pregestational diabe-tes, which may be undiagnosed before pregnancy. Also,there is concern about whether the found associationwith autism is causal, or there is a maternal factor thatis contributing to the obesity, which then increases the

risk of developmental problems, including autism. At thispoint, we need more information and the study needsto be replicated. Nonetheless, Dr. Wiznitzer noted that ifthe study's results can influence women to better man-

age their weight and overall health before and duringpregnancy, this would be a major strength.

Indeed, this kind of intervention can start in responseto parental concerns. Pediatricians should acknowledgeand address parents with concrete advice for how topromote a child's development, whether or not the child

has a specific diagnosis. Although the parents of childrenwith developmental delays oen request guidance onhow to interact more effectively with their children, apediatrician's goal should be to place the child's be-haviors in a clinical framework and to offer strategiesthat work within this exact framework. In the case of achild with a difficult temperament, such as being slowto warm up or having a negative mood or impulsive/emotional liability, this may begin with a discussion ofthe concept of temperament, administration of a tem-perament scale to the parent and child, and discussion

of "goodness of fit" (11). For the child with socializationdelays, this may involve a referral to ’Early Intervention’(federally mandated service for children with disabilities),a play group, or introducing the parents to Greenspanand Wieder’s (12) concept of "floortime" and "closingcircles of communication", so that they can begin thisintervention at home. Parents of children whose lan-guage acquisition seems questionable for their age canbe advised to use picture books to name objects, tellstories, point and name common objects in the home,and provide an ongoing description of their activities.Picture books also provide a vehicle for parents to sup-

port joint attention. A close clinical follow-up how thechild responds to these interventions may be informa-tive diagnostically, but clinical presentation is initiallyunclear. While suggesting these activities, clinicians whorecognize delays in behavior, socialization, and com-munication need to raise the possibility of ASD andmake appropriate referrals for developmental, speech,language, and audiological assessments. Encouragingparents to become their child's primary therapist is notappropriate. Parents need tools so that they can interactwith, understand, and advocate for their child, but the

onus for appropriate referral, diagnosis, and treatmentlies with the pediatric provider.In conclusion, using the translational research ap-

proaches we may close that gap and improve healthcare quality by improving access, reorganizing andcoordinating systems of care, helping clinicians andpatients to change behaviors and make more informedchoices, providing reminders and point-of-care decisionsupport tools, and strengthening the patient-clinicianrelationship.

REFERENCES

  1. Stotland N.E.: Obesity and pregnancy. BMJ 2008; 337: a2450.

  2. Krakowiak P., Walker C.K., Bremer A.A., Baker A.S., Ozonoff

S., Hansen R.L., Hertz-Picciotto I.:  Maternal metabolic

ents' knowle ge an observational skills. is increaseawareness shoul improve i entification of aberrationsin typical evelopment an behavior to a vance earlyi entification of ASD. us, the final step in i entifyingASD may inclu e watchful waiting (also calle : watchan wa t, expectant management, or act ve surve ance

(9) ), which nee s to be applie to the entire stu y cohortin a pe iatric/family practice office as a recommen eapproac to agnose A n c ren w t a me caproblem relate to obesity uring the mothers pregnancy.Obviously, uring that time, repeate testing for ASD must

e on y per orme y qua e me ca personne . skin of intervention buil s on prior research, inclu ingstu ies that emonstrate the a vantage of tailore inter vent ons as compare to gener c or targete es gns 1 .

In the time of ever-expan ing nowle ge about anintense focus on autism, there is a major concern on

how pe iatricians shoul respon to parental concerns.ough pe iatricians may not always have the answers,they will not go wrong if they listen to parents an ac-knowle ge their concerns. e message "wait an see"is un erstan ably a battle cry to parents who worry thattheir chil ren have true elays. Chil ren with atypicalsocial/emotional evelopment as to lers may ultimatelybe iagnose with ASD, a language isor er, cognitive

elay, sensory integration ysfunction, attention- eficit/hyperactivity isor er, or merely a challenging temperament by the time they are school age . In the face ofparenta concern, t e cr t ca ssue or pe atr c ans s to

istinguish chil ren with a problem requiring an imme iate, intensive intervention from one for whom watchfulwa t ng s appropr ate. A t ona y, a ey component owatchful waiting is the use of an explicit ecision treeor other protocols to ensure a timely transition fromwatc u wa t ng to anot er orm o management, asnee e . is is particularly common in postsurgicalmanagement of cancer survivors, in whom cancer recurrence s a s gn cant concern.

lthough there was a relationship between obesityan autism, the concept itself is obviously controversial

since there was also a very mo est association founbetween the evelopmental isor ers an iabetes(2). For example, Dr. Max Wiznitzer, who is also theneurology liaison to the Autism Subcommittee for theAmerican Aca emy of Pe iatrics, recently state that thereal question is about the interpretation of Krakowiaksresults (CNN Health, April, 2012). For example, obesewomen have an increase ris for pregestational iabetes, which may be un iagnose before pregnancy. Also,there is concern about whether the foun associationwith autism is causal, or there is a maternal factor thatis contributing to the obesity, which then increases the

ris of evelopmental problems, inclu ing autism. At thispoint, we nee more information an the stu y nee sto e rep cate . onet e ess, r. zn tzer note t atthe stu y's results can influence women to better man

age their weight an overall health before an uringpregnancy, this woul be a major strength.

In ee , this in of intervention can start in responseto parental concerns. Pe iatricians shoul ac nowle gean a ress parents with concrete a vice for how topromote a c s eve opment, w et er or not t e c

has a specific iagnosis. Although the parents of chil renwith evelopmental elays oen request gui ance on

ow to nteract more e ect ve y w t t e r c ren, ape iatrician's goal shoul be to place the chil 's behaviors in a clinical framework an to offer strategiest at wor w t n t s exact ramewor . n t e case o achil with a ifficult temperament, such as being slowto warm up or having a negative moo or impulsive/emot ona a ty, t s may eg n w t a scuss on othe concept of temperament, a ministration of a temperament scale to the parent an chil , an iscussion

of "goo ness of fit" (11). For the chil with socializationelays, this may involve a referral to Early Intervention(fe erally man ate service for chil ren with isabilities),a play group, or intro ucing the parents to Greenspanan Wie ers (12) concept of "floortime" an "closingcircles of communication", so that they can begin thisintervention at home. Parents of chil ren whose language acquisition seems questionable for their age canbe a vise to use picture books to name objects, tellstories, point an name common objects in the home,an provi e an ongoing escription of their activities.Picture books also provi e a vehicle for parents to sup-

port joint attention. A close clinical follow-up how thechil respon s to these interventions may be informat ve agnost ca y, ut c n ca presentat on s n t a y

nclear. While suggesting these activities, clinicians whorecognize elays in behavior, socialization, an commun cat on nee to ra se t e poss ty o A anmake appropriate referrals for evelopmental, speech,language, an au iological assessments. Encouragingparents to ecome t e r c s pr mary t erap st s notappropriate. Parents nee tools so that they can interactwith, un erstan , an a vocate for their chil , but the

onus for appropriate referral, iagnosis, an treatmentlies with the pe iatric provi er.In conclusion, using the translational research ap-

proaches we may close that gap an improve healthcare quality by improving access, reorganizing ancoor inating systems of care, helping clinicians anpatients to change behaviors an ma e more informechoices, provi ing remin ers an point-of-care ecisionsupport tools, an strengthening the patient-clinicianrelationship.

REFERENCES

  1. Stotland N.E.: Obesity and pregnancy. BMJ 2008; 337: a2450.

  . Kra owia P., Wa er C.K., Bremer A.A., Ba er A.S., Ozono

S., Hansen R.L., Hertz-Picciotto I.:  Maternal metabolic

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conditions and risk for autism and other neurodevelopmental

disorders. Pediatrics 2012; 129: e1121-e1128.

  3. Tuah N.A., Amiel C., Qureshi S., Car J., Kaur B., Majeed A.: 

Transtheoretical model for dietary and physical exercise

modification in weight loss management for overweight

and obese adults. Cochrane Database Syst Rev 2011; (10):

CD008066. (Issue 2-2012).  4. Prochaska J.O., Redding C.A., Evers K.E.: e transtheoretical

model and stages of change. In: Glanz K, Rimer BK, Viswanath

K (Eds). Health Behavior and Health Education. eory,

Research, and Practice. Jolley-Bass, San Francisco, CA, 2008.

  5. Campbell F., Johnson M., Messina J., Guillaume L., Goyder

E.: Behavioural interventions for weight management in

pregnancy: a systemic review of quantitative and qualitative

data. BMC Public Health 2011; 11: 491-506.

  6. Wiseman N.D.: Autism: A Parent's Guide to the First Signs

and Next Steps. Broadway Books, New York, NY, 2006.

  7. Glascoe F.P.: Parents' evaluation of developmental status:how well do parents' concerns identify children with

behavioral and emotional problems? Clin Pediatr (Phila)

2003; 42: 133-138.

  8. Senator S.: Making Peace with Autism: One Family's Story

of Struggle, Discovery, and Unexpected Gis. Trumpeter,

Boston, Mass., 2005.

  9. Meredith L.S., Cheng W.J., Hickey S.C., Dwight-Johnson

 M.: Factors associated with primary care clinicians' choice

of a watchful waiting approach to managing depression.

Psychiatr Serv 2007; 58: 72-78.10. Hawkins R.P., Kreuter M., Resnicow K., Fishbein M., Dijkstra

 A.: Understanding tailoring in communicating about health.

Health Educ Res 2008; 23: 454-466.

11. Chess S., omas A.: Temperament in Clinical Practice.

Guilford Press, New York, NY, 2005.

12. Greenspan S., Wieder S.: Engaging Autism: Helping Children

Relate, Communicate and ink with the DIR Floortime

Approach. Da Capo Press, Cambridge, Mass., 2006.

Received: September 10, 2012

Accepted: September 17, 2012

Address for correspondence:Wlodek Lopaczynski

8120 Paisley PlacePotomac, MD 20854

E-mail: wlopaczynski@hotmail.com