REVIEW Using Natural Disasters to Study the Effects of ... · PNMS research with humans is also limited ... related to developmental windows in gestation. In addition, the researcher

Using Natural Disasters to Study the Effects ofPrenatal Maternal Stress on Child Health andDevelopment

Suzanne King,* Kelsey Dancause, Anne-Marie Turcotte-Tremblay,Franz Veru and David P. Laplante

Research on the developmental origins of health and disease highlights theplasticity of the human fetus to a host of potential teratogens. Experimentalresearch on laboratory animals has demonstrated a variety of physical and be-havioral effects among offspring exposed to prenatal maternal stress (PNMS).However, these studies cannot elucidate the relative effects of the objectivestress exposure and the subjective distress in a way that would parallel thestress experience in humans. PNMS research with humans is also limitedbecause there are ethical challenges to designing studies that involve the ran-dom assignment of pregnant women to varying levels of independent stressors.Natural disasters present opportunities for natural experiments of the effects ofpregnant women’s exposure to stress on child development. In this review, wepresent an overview of the human and animal research on PNMS, and highlightthe results of Project Ice Storm which has been following the cognitive, behav-ioral, motor and physical development of children exposed in utero to theJanuary 1998 Quebec Ice Storm. We have found that both objective degree ofexposure to the storm and the mothers’ subjective distress have strong and per-sistent effects on child development, and that these effects are often moderatedby the timing of the ice storm in pregnancy and by the child’s sex. BirthDefects Research (Part C) 96:273–288, 2012. VC 2013 WileyPeriodicals, Inc.

Key words: prenatal maternal stress; disaster research; newborn andchild outcomes

INTRODUCTIONAs early as biblical times, it was rec-ognized that stress to a pregnantwoman could have serious conse-quences for her unborn child (e.g.,Exodus 21:22; 1 Samuel 4:19).Since the 1970s, retrospective epi-demiological studies have foundthat prenatal maternal stress(PNMS) increases risk for a variety

of negative outcomes to the off-spring, including preterm birth(Paarlberg et al., 1995) and severemental illness (Huttenen and Niska-nen, 1978), among others (Bey-doun and Saftlas, 2008; Weinstock,2008; Cottrell and Seckl, 2009;Charil et al., 2010; DiPietro, 2012).

Understanding the mechanismsof the PNMS effect in humans, how-

ever, poses a variety of theoretical,ethical, and logistical difficulties.First, there are several, competinguses of the term “stress”. HansSelye (1956) adapted the termfrom the field of mechanics to thefield of psychology. In mechanics,the term stress is used to reflect ameasure of physical force on anobject; in the social sciences, it hasbeen used in a variety of ways. Inpsychology, stress may be used todescribe the objective, externalforces acting upon an individual(i.e., the “stressor”), or the effectsof those forces as experiencedsubjectively (i.e., “distress”) orphysiologically as reflected, forexample, in neuroendocrine meas-ures. Research on prenatal mater-nal stress may cover any and all ofthese meanings.Ethically, stress in pregnancy is

difficult to study in humans usingexperimental methods, which arethe gold standard criterion for mak-ing causal conclusions. Althoughanimal research allows for randomassignment of pregnant animals toa variety of severe stress condi-tions, this is not ethically accepta-ble with humans. Research withlaboratory animals is informative

REVIE

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Suzanne King, Kelsey Dancause, Franz Veru are from the Douglas Hospital Research Centre, Psychosocial Research Division,Quebec, Canada, and Department of Psychiatry, McGill University, Montreal, Quebec, CanadaAnne-Marie Turcotte-Tremblay is from the Global Health Research Capacity Strengthening Program, University of Montreal,Hospital Research Centre (CRCHUM), Montreal, Quebec, CanadaDavid P. Laplante is from the Douglas Hospital Research Centre, Psychosocial Research Division, Montreal, Quebec, Canada

*Correspondence to: Dr. Suzanne King, Douglas Hospital Research Centre, Psychosocial Research Unit, Douglas Mental Health Univer-sity Institute, 6875 LaSalle Blvd., Verdun, Quebec H4H 1R3, Canada. E-mail: [email protected]

Supported by grants from the Stairs Memorial Fund of McGill University, Fonds de la recherche en sant�e du Qu�ebec: Axe Schizophre-nie, and the Canadian Institutes of Health Research (CIHR; MOP-57849, MOP-79424, MOP-111177) and by research fellowships fromthe Fonds de recherche en sant�e du Qu�ebec (King) and from CIHR and the National Institutes of Health (Dancause; postdoctoral fel-lowships).

View this article online at (wileyonlinelibrary.com). DOI: 10.1002/bdrc.21026

Birth Defects Research (Part C) 96:273–288 (2012)

VC 2013 Wiley Periodicals, Inc.

regarding the effects of objectivestress exposure and physiologicalindices of stress, but cannot informus about the animals’ subjectiveexperience of distress. Oneapproach to the ethical research ofstress during pregnancy withhumans has been to study thestress from naturally occurringevents, such as job loss or maritalseparation, to determine how thesecorrelate with obstetrical and childoutcomes. Unfortunately, for theresearcher, few women experiencesevere life events during pregnancythat would qualify as “independent”stressors: these would be eventsthat the woman could not possiblyhave influenced herself through ei-ther behavioral or genetic means,either of which could have its owneffects on the child outcomes ofstudy. A woman who is fired fromher job or who separates from herpartner while pregnant, for exam-ple, may have traits that influencedthe likelihood of her experiencingthe event and which she alsopasses on to her child genetically orthrough behavioral modeling.

Logistical challenges arise whenattempting to design the idealstudy. It would be imperative toidentify pregnant women under-going a severe, independent lifeevent to be able to isolate threedimensions of stress: the degreeof objective exposure to the stres-sor, the level of subjective distress,and the woman’s physiologicalresponse to the stressor. As well,the onset of the stressor wouldneed to be sudden and discrete topinpoint the timing of the exposurein pregnancy, such that it can berelated to developmental windowsin gestation. In addition, theresearcher would need access tolarge numbers of pregnant womenexperiencing the event to havesufficient sample sizes foradvanced analyses. Finally, thataccess would need to occur veryquickly after the event so thatstress levels can be measuredbefore women exposed in the lastweeks of pregnancy give birth, topreserve the prospective nature ofthe study.

Our approach for the past 15years has been to study pregnant

women experiencing natural disas-ters. A disaster is any event thatcauses “disruption exceeding theadjustment capacity of the affectedcommunity” (Lechat, 1979). Natu-ral disasters by their nature tendto have sudden onsets and to beindependent of the control of indi-viduals. Using disasters for naturalexperiments presents an approxi-mation of the randomizationafforded by true experiments, andcapitalizes on the relatively largepotential subject pool following adisaster occurring in a large com-munity. To date, we have threesuch studies underway, each onewith an initial sample between 200and 300 women. Project Ice Stormbegan in June 1998, studying theeffects of the January 1998 Que-bec ice storm on pregnant womenand their unborn children. TheIowa Flood Study recruited preg-nant women exposed to severefloods in June 2008, and improvesupon Project Ice Storm by includ-ing a subsample of women withextensive psychosocial measurestaken before the disaster struck,rendering it the world’s firstpre–post disaster study in preg-nant women. Finally, the QF2011Queensland Flood Study, under-taken shortly after the January2011 flooding in Brisbane, Aus-tralia, improves upon the previousstudies by piggy-backing on a pre-existing randomized control trial oftwo forms of prenatal care,thereby including not only preflooddata on a subsample, but also test-ing a potential intervention.QF2011 also included the samplingof placentas and other tissues thatcontain precious clues about thebiological cascades underlying theeffects of PNMS.

In this review, we will outlinewhat we have learned about theeffects of PNMS by taking advant-age of these natural experiments.We will focus on the results of Pro-ject Ice Storm, which as the first-born and oldest study, has themost complete set of results.

PROJECT ICE STORMProject Ice Storm was initiated

soon after a series of ice storms

struck southern Quebec from Janu-ary 5 to 9, 1998, dropping 10 cmof freezing rain on the region. Theweight of the ice damaged 3000hydroelectric pylons and toppled30,000 wooden electric poles,knocking out electricity for morethan 3 million people in 700municipalities for as long as 45days. The ice storm caused 35deaths, directly or indirectly. Theeconomic costs of the 1998 icestorm to the province are esti-mated at $1.5 billion (EnvironmentCanada, 2003), and the storm hasbeen counted as the worst andmost costly natural disaster in Ca-nadian history (Insurance Bureauof Canada, 2012).On June 1, 1998, we mailed

questionnaires to women inseverely affected regions south-east of Montreal, whose doctorsidentified them as being pregnantduring the ice storm, or whobecame pregnant within 3 monthsof the storm; this latter“preconception exposed” groupwas included to test hypothesesabout effects of stress before con-ception. Our Storm32 question-naire assessed four categories ofobjective disaster exposure: threat(e.g., being injured or in danger ofinjury), loss (e.g., financial, homedamage), change (e.g., staying ina shelter, housing others), andscope (days without electricity andtelephone) (see Laplante et al.,2007 for details). The 224 womenin our initial sample spent up to 15days in temporary shelters, and anaverage of 15 days (0–42) withoutelectricity in their homes duringthe crisis, when daily low tempera-tures dropped to between 210 and220�C. The extent of objectivestress from the ice storm as meas-ured by Storm32 appears to havebeen randomly distributed, with noassociation with socioeconomicstatus.To estimate the women’s subjec-

tive distress reaction to the icestorm, we used a validated Frenchversion (Brunet et al., 2003) of theImpact of Events Scale-Revised(IES-R) (Weiss and Marmar,1997), which assesses posttrau-matic stress symptoms in threecategories: avoidance, intrusive

274 KING ET AL.


thoughts and images, and hyperar-ousal. To assess maternal diurnalcortisol secretion, the postal ques-tionnaire also included a salivasampling kit consisting of num-bered strips of filter paper, instruc-tions, and a stamped return enve-lope. Women were requested totake six samples of salivary corti-sol at defined times between wak-ing and bedtime on the first dayand then a seventh upon wakingon the second day. After the sam-ples were collected, they were an-alyzed using a competitive bindingradioimmunoassay. Calculations ofthe area under the curve using thetrapezoidal rule, and averagehourly rates of salivary cortisol(integrated cortisol: ng/ml/hr)were used in analyses. We alsoassessed the women’s trait anxietyand depression at each assess-ment, and controlled for maternalsymptoms in all analyses.

Project Ice Storm families haveparticipated in up to a dozenwaves of assessments to date.Questionnaires have been com-pleted almost annually, and face-to-face assessments of childrenwere done at ages 2, 51=2, 81=2,111=2, and 131=2 years. The familiesin our study are better educatedand have higher incomes than theregional averages. More detaileddescriptions of the sample andmethods can be found elsewhere(Laplante et al., 2004; King andLaplante, 2005; Laplante et al.,2007; Laplante et al., 2008; Kinget al., 2009b; Dancause et al.,2011, Dancause et al., 2012).

Our findings demonstratemoderate-to-large effects of PNMSfrom the ice storm on the develop-ment of these children, a fact thatis especially impressive given theadvantaged upbringing of most ofthem. In the following sections, wepresent a brief overview of theexisting literature on the effects ofPNMS, and then describe ProjectIce Storm findings showing effectson physical growth (birth outcomesand childhood obesity), neurode-velopmental clues (neuromotorfunctioning and finger ridgecounts), medical illnesses and out-comes (asthma and metabolism),behavioral development (e.g.,

internalizing, externalizing, andsubclinical autistic-like behaviors),and cognitive development (IQ andlanguage).

PHYSICAL GROWTH

Birth outcomesStress during pregnancy seems

to have adverse effects on fetalgrowth as evidenced by physicalmeasurements at birth. For exam-ple, human studies have shownassociations between smaller birthweight or head circumference, aswell as shorter gestation length,and pregnancy-related stress oranxiety (Kramer et al., 2009), lifeevents (Lou et al., 1994; Hede-gaard et al., 1996; Lu and Chen,2004; Khashan et al., 2009), andanxious (Mancuso et al., 2004) ordepressive (Orr et al., 2002;Andersson et al., 2004; Dayanet al., 2006) symptoms. In gen-eral, early-pregnancy to midpreg-nancy appears to be the most sen-sitive period (although thisdepends on the outcome studied),and effects often vary by the sexof the newborn.

In Project Ice Storm, regressionanalyses (controlling for potentialconfounding variables) indicatedeffects of PNMS due to the stormon birth weight, length, and headcircumference, with effectsdepending on stress type, timing,and the baby’s sex (Dancauseet al., 2011). Mere exposure to theice storm appears to have had aneffect on some aspects of growth:mean birth length for gestationalage in the full sample was nearlyone-third of a standard deviationsmaller than Canadian populationreferences; although ours is not arepresentative sample of theregion, the socioeconomic statusof our sample should have pre-dicted average, or larger than av-erage, babies at birth.

Some birth outcome results im-plicate timing and/or the severityof the mother’s objective stressexposure or subjective distress.For example, mid-pregnancy andlate-pregnancy exposure had littleimpact on head circumference, butearly exposure to high levels ofsubjective PNMS predicted smaller

circumferences. Similarly, highersubjective PNMS levels predictedlower birth weights in general, withexposure in midpregnancy havingthe greatest impact. Length atbirth was shortest among infantsof women with a “discrepancy”between their objective and sub-jective PNMS levels: that is, amongwomen who had low levels of sub-jective distress in response to highlevels of objective stress, with theeffect greatest among boys; orwho had high levels of subjectivedistress in response to relativelylow levels of objective stress,especially for girls (Fig. 1). Sex dif-ferences were also observed forhead circumference-to-birth lengthratios: subjective PNMS had littleeffect on girls’ ratios, but a markedeffect on boys’, with higher subjec-tive PNMS levels predicting smallerhead circumference relative tobirth length among male infants.The effects of PNMS on this ratiosuggests the possibility that a“brain sparing” process was atwork in male fetuses, such thathigh maternal distress from the icestorm triggered a shunting of fetalresources to preserve the head atthe expense of body length.All of these effects were modest,

but considering the continued pub-lic health burden posed by adversebirth outcomes (Hobel et al.,2008), even modest effects mightbe relevant, especially where riskis already elevated due to knowncontributing factors, such as pov-erty, and where psychosocialstress might exacerbate this risk.

Body mass index and obesityAlthough data are still limited,

PNMS is increasingly accepted as arisk factor for obesity in childhoodand adulthood. This might reflectthe effects of PNMS on fetal growthpatterns, since low birth weightand intrauterine growth restrictionare associated with increased riskfor later cardiometabolic diseases,such as obesity, hypertension, andinsulin resistance (Barker, 2004;Eriksson, 2005). Furthermore,PNMS might result in deregulationof the fetal hypothalamic pituitaryadrenal (HPA) axis (Sandman

NATURAL DISASTERS AND PRENATAL MATERNAL STRESS 275


et al., 1994), which is involved inmetabolic pathways (Nieuwenhui-zen and Rutters, 2008) and likelyrepresents a mediating mechanismin the developmental origins ofhealth and disease (Drake et al.,2007; Beydoun and Saftlas, 2008;Cottrell and Seckl, 2009; Entringeret al., 2010; Entringer et al.,2012). Human studies have shownassociations between obesity andmeasures of adiposity in childrenand young adults with maternalbereavement (e.g., due to thedeath of a spouse) during orshortly before pregnancy (Li et al.,2010), stressful life events duringpregnancy (Entringer et al., 2008b,Entringer et al., 2010), and higherlevels of maternal corticotrophin-releasing hormone, which providesa marker of fetal glucocorticoid ex-posure (Gillman et al., 2006).

We observed similar effects ofPNMS due to the ice storm onchildren’s body mass index (BMI)(Dancause et al., 2012). The se-verity of the mothers’ objectivestress exposure from the ice stormexplained 5% of unique variance inthe children’s BMI, even after tak-ing maternal height and the child’sbirth weight into account, withgreater stress being associatedwith larger BMI. In addition, con-trolling for potential confoundingvariables, objective PNMS wasassociated with increased obesityrisk among children at age 51=2,with odds ratios (OR) ranging from1.37 to 1.43, depending on themodel tested. Similar effects werealso seen at ages 81=2 and 111=2years (unpublished data). These

effects were independent of size atbirth, suggesting that PNMS mightincrease obesity risk througheffects on metabolic pathways. Forexample, PNMS might result in thereorganization of neural pathwaysinvolved in appetite regulation andmetabolism, and a subsequent“reprogramming” of energy bal-ance (Bouret, 2009; Entringeret al., 2010; Eriksson, 2010). Thiscould increase risk independentlyof size at birth, as well as potentialconfounders such as socioeco-nomic status. More human studiesare necessary to clarify the mecha-nisms underlying the programmingeffects of PNMS on cardiometabolicoutcomes, and their persistenceacross the lifespan.

COGNITIVE DEVELOPMENT

AND LANGUAGE

It is widely accepted that pertur-bations during fetal developmenthave lasting effects on cognitiveand language abilities. In general,maternal stress and/or anxiety dur-ing pregnancy result in less thanoptimal neurodevelopment in bothanimals and humans (O’Donnellet al., 2009; Charil et al., 2010).How prenatal stress and anxietyimpact cognitive and language de-velopment remains largelyunknown. Because maternal andfetal cortisol levels are highly corre-lated (Gitau et al., 2001), it isbelieved that increased levels ofmaternal stress and/or anxietyresult in glucocorticoid levels thatexceed the placenta’s ability to con-vert cortisol to cortisone, thereby

exposing the fetus to levels of corti-sol that may disrupt neuronal de-velopment. However, it has beendemonstrated that relatively lowlevels of maternal stress and/oranxiety may have a positive influ-ence on cognitive development(DiPietro et al., 2006; DiPietro etal., 2010). As such, the exact na-ture of the relationship betweenpregnancy-related maternal stressand/or anxiety and these outcomesremains unclear.To date, we have data on the

cognitive and language abilities ofchildren in the Project Ice Stormcohort at ages 2, 51=2, 81=2, 111=2,and 131=2 years. Cognitive func-tioning was assessed usingstandardized face-to-face IQ testsat every age (Bayley, WPPSI, andWISC).All results presented here reflect

the children’s cognitive (Fig. 2)and language (Fig. 3) abilities afteradditional maternal (e.g., socioe-conomic status, age, major lifeevents, and/or trait anxiety) and/or child (e.g., gestational age, birthweight) control variables havebeen accounted for in the analy-ses. Due to budgetary restrictions,our 2 year old sample containsonly children whose mothers expe-rienced either low or high levels ofobjective stress; children whosemothers experienced moderatelevels of objective stress were notassessed. Children exposed inutero to moderate levels of objec-tive stress were included in theanalyses at all subsequent ages.Our initial assessment of the chil-

dren at age 2 years indicated that,

Figure 1. Interaction between objective stress and subjective PNMS for birth length as a function of newborn sex.

276 KING ET AL.


on average, children who wereexposed in utero to high levels ofobjective stress from the ice stormhad Mental Development Indexscores (Bayley version of an IQscore) that were a full standarddeviation lower than that of childrenexposed to low levels of maternalobjective stress (Laplante et al.,2004). Moreover, the effect ofobjective stress was more pro-nounced in children exposed to theice storm during the first or secondtrimester than during the third tri-mester. Interestingly, there were noeffects of maternal subjectivedistress.

Similar findings were observedwhen we assessed the children’splay. Because a child’s perform-ance on a formal intelligence test

may be partly a function of theirtemperament and behavior prob-lems, that is, how compliant and atease they may be with the exam-iner, we also completed assess-ments of the children’s style ofplay. We assessed the maturityand breadth of the children’s playat 2 years of age using a standar-dized protocol developed by Zelazoand Kearsley (1980). Videotapeswere coded to determine the per-centage of time the children spentin stereotypical play, in moremature relational play, or in evenmore mature functional play. Com-pared to children exposed in uteroto low levels of objective stress,those whose mothers experiencedhigh levels of objective stressexhibited a higher percentage of

immature stereotypical play (14.3vs. 5.8%), lower levels of maturefunctional play (41.9 vs. 60.7%),and fewer functional acts with thetoys (10.1 vs. 15.2 acts) (Laplanteet al., 2007). As with the children’sBayley scores, differences in toyplay were greatest in childrenexposed to the ice storm duringthe first or second trimesters.Unlike results from the Bayley,however, maternal subjective dis-tress from the ice storm explainedsignificant amounts of variance inthe children’s performance: objec-tive and subjective PNMSaccounted for 13.4 and 12.8% ofthe variance of the children’s func-tional play levels, respectively.Language development was

assessed using standardizedinstruments at the same ages asthe IQ testing. At age 2 years, af-ter controlling for the toddlers’birth weight, mothers who experi-enced high levels of objectivestress during the first or secondtrimester reported that their chil-dren understood 10 fewer words,and spoke 19 fewer words, relativeto toddlers whose mothers experi-enced low levels of objectivestress (Laplante et al., 2004).Objective stress accounted for asignificant 12 and 17% of the var-iance in the number of wordsunderstood and spoken by thetoddlers.These results suggest that expo-

sure in utero to high levels ofmaternal stress resulting from anatural disaster negatively impactscognitive and language develop-ment in young children. Moreover,the play of the 24-month old tod-dlers exposed in utero to high lev-els of objective stress were compa-rable to those of a group ofnormally developing 151=2 month-old toddlers who had beenassessed by Zelazo and Kearsley(1980). Together, these findingssuggested that the ice stormcohort’s performance on thesetasks appeared to be delayed, sim-ilar to that of children born prema-turely. As with most prematurechildren, we believed that the per-formance of children exposedin utero to high levels of maternalstress would improve with age.

Figure 2. IQ scores at 2, 51=2, 81=2, and 111=2 years of age as a function of objectivestress.

Figure 3. Language scores at 2, 51=2, 81=2, and 111=2 years of age as a function ofobjective stress.



The effects of prenatal maternalobjective stress on cognitive andlanguage development were repli-cated at age 51=2, but with twointeresting twists (Laplante et al.,2008). First, we included the mod-erate objective stress group in theassessments at this age, whichrevealed a curvilinear associationbetween PNMS, and both IQ andlanguage: scores were higher in themoderate objective stress groupthan in either the low or, especially,the high stress groups. This findingis similar to that reported byDiPietro et al., 2006; DiPietro et al.,2010), and suggests that exposureto some level of stress by the fetusduring prenatal development maybe beneficial. However, the optimalamount of exposure has yet to bedetermined. Secondly, there wasno longer a trimester of exposureeffect in the results. As before,however, there were no effects ofsubjective distress on either IQ orlanguage. These patterns wererepeated at age 81=2 (unpublisheddata), but then varied by sex at age111=2 (unpublished data).

Our findings are surprising ontwo accounts. First, contrary to ourexpectations, maternal subjectivedistress did not account for any ofthe variance in the children’s psy-chometrically assessed cognitiveor language abilities during child-hood; maternal subjective distresslevels did, however, account for

moderately large amounts of var-iance in the children’s play at age2 years. We suspect that, becausethe ice storm affected everybodyin the region to some degree, theevents and experiences thesewomen faced were sufficientlystrong to alter the fetal environ-ments of their children, even inwomen who perceived the disasteras not being distressing. Second,also contrary to our expectations,the effects of the PNMS exposureon the children have not dissipatedwith increasing age. While theoverall magnitude of the differencein cognitive and language abilitiesof children exposed to high versusmoderate or low levels of PNMSwas halved between 2 and 51=2years of age, the differenceremained relatively stable between51=2 and 111=2 years of age,particularly in boys, suggestingmild, but permanent alterations inperformance.

NEURODEVELOPMENT

Neuromotor developmentResearch suggests that high lev-

els of PNMS or maternal cortisolduring pregnancy are associatedwith poorer motor outcomes atbirth (Rieger et al., 2004; Ellmanet al., 2008) and within the firsttwo years of life (Buitelaar et al.,2003; Chuang et al., 2011). Thismight reflect effects of PNMS on

development of the cerebellum.Rodents exposed to prenatal stresslate in gestation exhibit a reducedvolume of granule cell nuclei andreduced synaptic density in thecerebellum, and a decrease in thecerebellar granule-to-Purkinje cellratio (Ulupinar and Yucel, 2005;Ulupinar et al., 2006). However,data from humans are limited, par-ticularly after infancy.We analyzed balance, bilateral

coordination, and visual motorintegration (VMI) skills among Pro-ject Ice Storm children at age 51=2(Cao et al., in press). Controllingfor potential confounding variables,we failed to find effects of PNMSon balance, but did observe signifi-cant effects of PNMS on bilateralcoordination and VMI. For bothbilateral coordination and VMI,boys’ coordination and VMI per-formance did not vary as a functionof the timing of exposure, but girls’performance was lower with expo-sure later in gestation (Figs. 4Aand 5A). Furthermore, objectiveand subjective PNMS had interac-tive effects, such that when sub-jective distress was high, perform-ance remained relatively poorregardless of objective stress lev-els; but when subjective distresswas low, there was a negative cor-relation between objective stressand coordination skills (Figs. 4Band 5B). These data provide sup-port for effects of PNMS on motor

Figure 4. Child sex and timing of exposure interaction (A) and objective and subjective PNMS interaction (B) observed in the child-ren’s bilateral coordination abilities at 51=2 years of age.

278 KING ET AL.


development that can persist intochildhood. Future analyses will testthe indirect effects of PNMS onmotor function via effects on spe-cific brain structures.

Fingerprint asymmetryPNMS has been implicated in a

number of mental conditions thatare presumed to have neurodeve-lopmental origins, such as schizo-phrenia (Weinberger, 1995; Talgeet al., 2007). Neurodevelopmentbegins at conception and is gener-ally not complete to adult levelsuntil the early 20s, when myelina-tion of the prefrontal cortex is fin-ished. The early prenatal periodlays down the initial foundations ofneural tube, then brain and spinalcord, followed by refinement of spe-cific brain structures, nerve cellmigration, and synaptic growth inlater stages. Conventional wisdomsuggests that stress to the preg-nant woman increases her gluco-corticoid levels, overwhelming theplacental barriers and disruptingdevelopment of whichever fetalsystems happen to be in ascend-ance at that time. Although it is cur-rently unfeasible to obtain directimages of neurodevelopment in thefetus as it unfolds, insults to neuro-development in utero may leavepermanent traces elsewhere onmore visible body parts that aredeveloping at the same time in ges-tation as the brain. In their reviewarticle, Tarrant and Jones (1999)

note that all minor and/or majorcongenital anomalies can be timedto specific stages of fetal develop-ment. For example, minor physicalanomalies of the feet reflect disrup-tion during gestation weeks 1–8,while abnormalities in the finger-prints may reflect disruption duringgestation weeks 14–22 (van Valen,1962). Fingerprint anomalies are oflittle interest in and of themselves.However, because fingerprintdevelopment occurs during the 2ndtrimester of gestation when criticalbrain structures (such as the hippo-campus) are also developing, andbecause fingerprints and brain de-velop out of the same fetal ectoder-mal tissue, and because finger-prints remain unchangedthroughout life, dermatoglyphicabnormalities may have importantimplications for developmentalpsychopathology.

We used the Project Ice Stormcohort to test the hypothesis thatPNMS would influence the symme-try of fingerprint ridge countsbetween homologous (that is, leftand right) fingers, but only forthose children whose mothersexperienced the ice storm at somepoint during the critical window offingerprint development: weeks14–22 (King et al., 2009b). Wepredicted that, for these children,greater PNMS would be associatedwith greater left–right asymmetry,as is seen in schizophrenia patients(Mellor, 1992; Weinstein et al.,1999; Reilly et al., 2001).

As anticipated, PNMS correlatedwith ridge count asymmetry in thechildren exposed in the targetweeks; the effect size for subjec-tive stress in this group could becharacterized as “very large”according to conventional criteria.Another aspect of the stress expe-rience is the mothers’ hormonalresponse as measured in salivarycortisol. Although we hypothesizedthat higher levels of diurnal cortisolin the women would be correlatedwith greater fingerprint asymme-try, we found a negativecorrelation instead: the lower thematernal cortisol levels, thegreater the fingerprint asymmetryin our target group. The mecha-nisms responsible for the surpris-ing direction of this associationelude us so far, but the fact thatthe saliva samples were taken sev-eral months following the ice stormmake it impossible to concludethat our results reflect the directeffects of maternal cortisol at thetime of the storm.The results of these fingerprint

analyses highlighted the need tolook directly at brain developmentin the ice storm cohort. We con-ducted structural brain imagingwhen the children were aged 111=2years and will report on thesefindings in the coming years. Ourultimate goal is to test thehypothesis that PNMS influencedthe development of particularbrain structures and had, thus,indirect effects on a number of

Figure 5. Child sex and timing of exposure interaction (A) and objective and subjective PNMS interaction (B) observed in the child-ren’s visual-motor integration abilities at 51=2 years of age.



observable child outcomes such aspsychopathology and neuromotordevelopment.

BEHAVIORAL DEVELOPMENT

Internalizing and externalizingproblems

A variety of social and environ-mental factors have been foundto be associated with thedevelopment of childhood psycho-pathology. For example, obstetriccomplications, smoking, and alco-hol consumption during pregnancy,low birth weight, socioeconomicstatus, parental marital status,parental pathology, and maternalage are all known to be associatedwith behavioral problems in chil-dren (Williams et al., 1998; Grayet al., 2004; Tremblay et al., 2004;Kahn et al., 2005; Najman et al.,2005). Recent research hasexplored the role that maternalstress and/or anxiety during preg-nancy has on the subsequent de-velopment of behavioral problemsduring childhood (O’Connor et al.,2003). For example, perceivedpregnancy-related stress wasfound to be positively correlatedwith observable externalizing prob-lems, such as aggressiveness anddestructiveness, in 2-year-oldtoddlers (Gutteling et al., 2005).Likewise, children whose mothersdisplayed high levels of anxietyduring the final month of their

pregnancy were two to three timesmore likely to display higher levelsof behavioral and emotional prob-lems at 4 years of age, relative tochildren whose mothers experi-enced low levels of anxiety, evenafter controlling for postnatalmaternal anxiety levels (O’Connoret al., 2003; Huizink et al., 2004;Van den Bergh and Marcoen,2004; Glover, 2011). As such, pre-natal maternal stress and anxietyare now considered potential riskfactors for the development ofpsychopathology in later life(Huizink et al., 2004).

Yet, how might one determinehow much of these effects are dueto the stressor versus the mothers’“distress” when the two aredifficult to disentangle? Nonhumanprimate research has found thateither mild daily social stress tothe mother (Schneider and Coe,1993) or 2 weeks of adrenocortico-tropic hormone treatment to themother at midgestation (Schneideret al., 1992; Weinstock, 2001)results in greater internalizingbehaviors, such as anxiety, ininfant monkeys. This work, andsimilar research in rodents, sug-gests that the independent,“objective” stressors imposed bythe researchers are sufficient toincrease risk for behavioral prob-lems in animals, and that thisstress has its effects via maternalstress hormones. However, as dis-

cussed above, animal researchcannot determine the relativeeffects of the subjective distressfrom the objective exposure.In Project Ice Storm, we ana-

lyzed maternal ratings of theirchildren’s internalizing problems(anxiety, depression, social with-drawal) (Fig. 6) and externalizingproblems (aggression, destructive-ness) (Fig. 7) assessed at ages 4,51=2, 61=2, 81=2, 91=2, and 111=2 years(King et al., 2009a). Zero-ordercorrelations between internalizingproblems and objective stress(Storm32) were low-to-moderateat each age, whereas correlationswith subjective distress (IES-R)were strong and significant atevery age (correlations range from0.348 to 0.512). Controlling formaternal depression and anxiety inJune 1998 following the ice storm,and also at the time of the assess-ment, subjective distress stillexplained an additional 8 to 12%of unique variance in internalizingproblems at each age. Results ofmultilevel modeling showed that,first, even though average scoresin this group have been below av-erage until recently, the severity ofinternalizing problems in this groupof children is increasing over timerelative to the norm group (i.e.,using standardized scores from themanual). Second, results showthat internalizing problems at 4years were predicted by subjectivematernal distress, which explained34% of the between-subjectsvariance in internalizing. Finally,objective and subjective PNMSinteract such that when the moth-er’s subjective distress was low,the greater her objective stressthe greater the child’s internalizingproblems; but when the mother’ssubjective distress was high, thechild’s internalizing problems aremore severe, and maternal objec-tive stress has no additional effect.Unlike internalizing problems,

externalizing problems in thesample appear to be lessening inseverity with age relative to thepublished norms, even though thegroup average has consistentlybeen below the published means.As with internalizing, the severityof the children’s externalizing

Figure 6. Internalizing problems at 4, 51=2, 61=2, 81=2, 91=2, and 111=2 years of age as afunction of subjective distress.

280 KING ET AL.


problems had low, positive correla-tions with objective maternalstress at all ages, but had strongercorrelations with subjective dis-tress (0.275–0.554). After control-ling for maternal mood, as above,subjective maternal distressexplained an additional 8 to 20%of unique variance in externalizingproblems. Multilevel modeling oftrajectories over time showed asignificant interaction betweenobjective and subjective PNMS thatparallels the results for internaliz-ing problems described above.

The effects of PNMS on behav-ioral development may be medi-ated by puberty and/or sex hor-mones. Huizink (2008) showedthat adolescent girls from a prena-tally stressed cohort had signifi-cantly higher testosterone levels atage 14 than a nonstressed com-parison group. Testosterone levelsin adolescence are associated withmore adverse alcohol consumptionand other antisocial behaviors(Eriksson et al., 2005). As ProjectIce Storm continues to monitorpsychological symptoms in thiscohort throughout adolescence, wewill also consider the role playedby puberty and androgens.

Autistic spectrum disordersOne way to study the effects of

PNMS on risk of severe psychopa-

thology is to use retrospectiveanalyses of prevalence rates andsee how these change due to ex-posure to severe weather eventsin utero. In a historical analysis ofthe impact of PNMS caused by 10severe weather events in Louisi-ana, Kinney et al. (1999, 2008)reported that rates of autism weresignificantly increased as a func-tion of prenatal exposure to stormsrated as severe by the NationalWeather Service, increasing theusual prevalence rate from 5 per10,000 births to 13 per 10,000births. Moreover, the impact ofthese storms was greatest for chil-dren exposed during certainmonths of the pregnancy, withprevalence rates for autism jump-ing to 18 per 10,000 births for chil-dren exposed to storms in months5 or 6 of gestation. Finally, stormseverity and timing interacted suchthat for children exposed inmonths 5 and 6 of pregnancy, forstorms classified as low, moderate,and severe intensity, the relativerisks for autism were 3, 10, and 27per 10,000 births, respectively.This is one of a handful of studiessuggesting that severity and timingof stress interact to influence riskof psychopathology.

In Project Ice Storm, we did notexpect any children to develop au-tism per se, but instead investi-gated subclinical autistic symp-

toms along a continuum (Kinget al., 2009a; Walder et al., Underreview). Mothers completed an au-tism screening questionnaire whenthe children were 6 years old. Sub-clinical autistic symptoms corre-lated significantly with objectivestress (r50.43), and with subjec-tive distress (r50.45). Combined,these two aspects of PNMSexplained about 23% of the var-iance in subclinical autistic symp-toms rated by mothers. There was,however, a significant interactionbetween objective and subjectivePNMS. High subjective distress lev-els were associated with highscores, regardless of the level ofobjective hardship. Objective hard-ship, however, was only related tohigh scores when subjective dis-tress levels were either low ormoderate in intensity. Finally, theobjective hardship 3 timing of ex-posure interaction explained addi-tional variance in scores: higherobjective hardship levels wereassociated with higher autistic-liketraits, only when the exposureoccurred early in the pregnancy.Together, these variables explained42.7% of the variance in thescores.Although Kinney found greater

susceptibility to autism in childrenexposed to tropical storms inmidgestation, we found that expo-sure in early gestation presentedgreater vulnerability to the effectsof PNMS.

MEDICAL ILLNESSES AND

OUTCOMES

MetabolismAs discussed above, PNMS has

been associated with later cardio-metabolic diseases, including dis-eases of glucose–insulin metabo-lism. Results from animal studiessuggest that prenatal exposure tohigh levels of maternal stress orglucocorticoids is associated withhyperglycemia and features of in-sulin resistance (Lindsay et al.,1996; Nyirenda et al., 1998; Mosset al., 2001; Cleasby et al., 2003;Lesage et al., 2004; Nyirendaet al., 2009). Furthermore, amonghumans, retrospective case–con-trol studies indicate increased risk

Figure 7. Externalizing problems at 4, 51=2, 61=2, 81=2, 91=2, and 111=2 years of age as afunction of subjective distress.



of insulin resistance among youngadults whose mothers experiencedstressors during pregnancy(Entringer et al., 2012). As in thecase of obesity, this might reflectdirect effects on metabolic path-ways, as well as indirect effectsthrough traits such as birth weightor adiposity (Entringer et al.,2012; Rinaudo and Wang, 2012).Based on the effects of PNMS onsize at birth (Dancause et al.,2011) and on childhood obesity(Dancause et al., 2012) in ProjectIce Storm, we hypothesized thatPNMS might affect glucose–insulinmetabolism in this cohort.

We conducted 30-min glucosetolerance tests among a subset of15 boys and 10 girls from ProjectIce Storm in adolescence (meanage 13.4 years) (Dancause et al.,under review). Despite the smallsample size, regression analysescontrolling for the adolescent’sbirth weight, percent body fat,pubertal stage, and number offamily members with diabetesshowed that greater levels ofobjective stress were associatedwith greater insulin secretion,explaining 15.7% of unique var-iance (Fig. 8), which is a feature ofinsulin resistance, increasing riskfor Type 2 diabetes.

These results support previousstudies suggesting that PNMS neg-atively affects metabolic health,and highlights that these effects

are manifest in adolescence. Asobserved for obesity, the effects ofPNMS on insulin secretion wereindependent of size at birth,suggesting effects on central medi-ators of metabolism. However,larger samples are needed to testthese potential mediating path-ways. As the global burden ofmetabolic disorders escalates(Danaei et al., 2011), the contribu-tion of PNMS to metabolic healthrepresents an important area ofresearch.

Immune FunctionThe ontogeny of the immune

system starts around the secondembryonic week and only reachesa mature state of development inlate childhood (West, 2002). How-ever, it is during intrauterine lifethat exogenous agents producemore notorious and long-lastingconsequences (Holladay and Smia-lowicz, 2000). Psychosocial stress,especially chronic stress, has beenfound to be immunosuppressive(Ashcraft and Bonneau, 2008).Such findings have motivated thesearch for the consequences ofstress exposure during pregnancy.

Most research on the effects ofPNMS on the immune system hasbeen conducted on animals. Con-sequences on the developingimmune system depend on thetype of stressor, the sex of the off-

spring, and the timing of exposurein gestation, as well as the type ofcell analyzed. For example,T helper lymphocyte percentageshave been found to be reduced inPNMS exposed animals (Llorenteet al., 2002; G€otz and Stefanski,2007; G€otz et al., 2007). In innatecells, Natural Killer cell cytotoxicityand phagocytic and oxidative burstcapacities in macrophages aredecreased in PNMS-exposed ani-mals, with marked sex differences(Kay et al., 1998; Fonseca et al.,2005; Coe et al., 2007). In adapt-ive cells, proliferative responsesincrease or decrease, dependingon the type of stressor, mitogen,and the stage of immune develop-ment (Sobrian et al., 1997;Tuchscherer et al., 2002). Humoralresponses may be enhanced insome cases, also depending onstressor-related factors (Klein andRager, 1995), while complexcellular responses (e.g., delayedtype hypersensitivity) are mostlydecreased (Gorczynski, 1992;Sobrian et al., 1997). This is con-sistent with the fact that cytokinefunction in the offspring has beenfound to be predominantly skewedtowards the production of Th2(anti-inflammatory) mediators fol-lowing PNMS (Coe et al., 2002;Pincus-Knackstedt et al., 2006;Vanbesien-Mailliot et al., 2007;Couret et al., 2009; Collier et al.,2011).To date, only two studies in

humans have explored the effectsof PNMS on mitogen-induced cyto-kine function. The first showedthat adult women whose mothersexperienced stressful life eventsduring pregnancy had a skewedpro-Th2 response (Entringer et al.,2008a). The second, using umbili-cal cord blood from babies whosemothers had faced multiple difficultlife circumstances, evidenced aTh2 shift in adaptive cytokines,whereas innate cytokines wereskewed towards Th1 (Wright et al.,2010). In Project Ice Storm, weare currently investigating theeffects of the mothers’ objectiveexposure and their subjective dis-tress on their children’s cytokinefunction in adolescence. In themeantime, we have indirect

Figure 8. Insulin secretion (insulinogenic index [(I30–I0)/(G30–G0); mU/mmol]) at13 years of age as a function of objective stress.

282 KING ET AL.


evidence of the effects of PNMS onimmune function by using mater-nal reports of children’s health, asreported in the next section.

AsthmaResearch has found that self-

reported maternal anxiety duringpregnancy explains variance in therisk for respiratory illnesses andasthma in children (Cookson et al.,2009; Beijers et al., 2010). Sinceboth animal and human studiessuggest that PNMS influences theimmune system in a sex-specificmanner, immune-mediated disor-ders such as asthma could also beinfluenced by PNMS. Indeed,according to Pincus-Knackstedtet al. (2006), prenatally stressedfemale mice were more at risk ofairway hyper-responsiveness,inflammation, as well as dysregu-lated pathways of cellular and hu-moral immune response. Inhumans, Pincus et al. (2010) foundthat low levels of maternal proges-terone, which can be triggered byactivation of the HPA axis, predictimmune disorders in girls only. Theplacenta may play an importantrole in the process by which PNMSdifferentially affects girls and boys.Genes related to immune path-ways are expressed differentially infemale compared to male placenta(Sood et al., 2006), and sex differ-ences are observed in placentalcytokine expression, insulin-likegrowth factor pathways, and pla-cental response to glucocorticoids(Clifton, 2010).

Building on such findings, wesought to examine whether disaster-related PNMS would increase riskof asthma in children from ProjectIce Storm (Turcotte-Tremblayet al., unpublished manuscript).Sixty-eight mothers participated ina brief telephone interview onasthma when their children, 32boys and 36 girls, were 12 years ofage. Lifetime asthma symptoms,diagnoses, and corticosteroidutilization were assessed using amodified version of the Interna-tional Study of Asthma and Aller-gies in Childhood questionnaire(Asher et al., 1995; Ellwood et al.,2005). Hierarchical logistic regres-

sion models indicated a gender-specific effect. In girls only, higherlevels of subjective distress fromthe storm were associated withgreater lifetime risk of wheezing(OR51.13), asthma as reported bythe mother (OR51.15), asthma asdiagnosed by a doctor (OR51.11),and lifetime utilization of cortico-steroids (OR51.29) (Fig. 9). Themothers’ objective stress scoresand timing of the stressor in preg-nancy did not predict asthma inthis sample.

Together with the existing litera-ture, these results highlight thecomplexity of the associationbetween PNMS and fetal program-ming of immune disorders. Thereis a need to produce evidence-based knowledge on the biologicalmechanisms by which a pregnantmother’s distress in the face of anatural disaster affects theimmune functioning of her childover time. We hope that our cyto-kine analyses from Project IceStorm, as well as results from thebirth biological samples fromQF2011 in Australia, will provideimportant clues to this question.

CONCLUSIONSOverall, the results from Project

Ice Storm suggest that more

severe PNMS from an independentstressor predicts worse perform-ance on assessments of cognitive,behavioral, and motor develop-ment, and have a significantimpact on a wide variety of physi-cal outcomes related to metabolicor immune function, body size,and putative neurodevelopmentalmarkers. The results for a particu-lar outcome vary, however, andimplicate either objective or sub-jective PNMS or their interaction,and may be moderated by the sexof the child or the timing of the icestorm in pregnancy.Results from this study are sur-

prising in a number of ways. First,we had not anticipated that the se-verity of the Quebec ice stormwould be sufficient to produce themoderate to very large effect sizesseen in our results. Although thestorm and its aftermath producedconsiderable hardship for largenumbers of people and for up to 6weeks or more, there was littleloss of life or real physical threatcompared to other recent eventsaround the globe, such as earth-quakes, hurricanes, tsunamis, andtornados. The fact that our sampleconsists of families from upper-middle and upper classes, and thatthe children are in the above-aver-age range of IQ with below

Figure 9. Percentage of lifetime wheezing, asthma (mother-rated and doctor-diag-nosed), and corticosteroid usage as a function of subjective distress and sex of thechild.



average behavior problems, makesthe magnitude of effects in this re-stricted sample even moreimpressive.

Second, we had expected thatthe effects of prenatal exposure tothe ice storm would not persistbeyond the first years of life, andthat variations in the postnatalenvironment would dilute and per-haps erase any prenatal stresseffects. Yet this has not been thecase, and effects are still seen inearly adolescence. Our currentresearch grant is allowing us toassess this cohort at ages 131=2and 15 years; results will giveinsights about the effects of PNMSthroughout adolescence.

Third, we have been struck bythe predictive power of the objec-tive stress score, which we origi-nally designed to be a simple con-trol variable. Our working model ofPNMS suggested that our subjectswould be confronted with varyingdegrees of hardship from thestorm, which may or may not cor-relate with their subjective dis-tress. Subjective distress wasexpected to be the “smoking gun”that would increase the pregnantwomen’s cortisol levels, whichwould have negative effects on thedeveloping fetus. Yet, we havefound that objective stress expo-sure has significant effects onphysical development (BMI, insulinsecretion), behavioral development(internalizing, externalizing, sub-clinical autistic symptoms), andespecially cognitive and languagedevelopment. To date, however,we have no explanation for thepower of objective stress in thissample. If this pattern holds in ourflood study in Australia, the birthbiological samples may provideclues to the mechanisms by whichobjective stress wields its effects.

Fourth, we were surprised by thecurvilinearity of the effects of objec-tive stress on cognitive develop-ment seen at ages 51=2 and 81=2years: scores on general intelli-gence, language, and memory (notshown) are highest in childrenwhose mothers had moderatescores on our objective stress mea-sure. This is especially astounding,given that Project Ice Storm does

not have a control group of familieswith no stress. The ice from thestorm covered much of southernQuebec and disrupted normal serv-ices and transportation for theentire population, including thosewho never lost power. There is a hy-pothetical subgroup of no-stresschildren whose cognitive perform-ance could be higher or lower thanthat of our low-stress group, butthere are no children in the icestorm study who were not exposedto PNMS. Both our Iowa and Austra-lian flood studies may provideclarity to the issue of the range ofstress exposure: both samplesinclude a wider range of hardship,from a complete absence ofinconvenience, to complete loss ofhouse and home resulting from theflooding. In the meantime, our cur-vilinear results echo similar PNMSresults of DiPietro et al., 2006 andDiPietro et al., 2010.

Study results demonstrate thatthe mother’s subjective distress,as reflected in the severity of post-traumatic stress disorder symp-toms assessed several months af-ter the storm, has significanteffects on a number of outcomes,including physical development(birth outcomes, fingerprint asym-metry) and asthma risk, but espe-cially strong effects on the behav-ioral and motor development ofthe children throughout childhood.The results suggest that, in someways, the mother’s subjective dis-tress “trumps” the effects of herobjective exposure to the hardshipfrom the storm. This is seen in theeffects on the children’s internaliz-ing and externalizing problems,subclinical autistic-like traits, andtheir bilateral coordination and vis-ual-motor integration: for each ofthese outcomes, performance waslowest for children whose mothershad high levels of subjective dis-tress, irrespective of their degreeof objective stress; but for childrenwhose mothers had low levels ofsubjective distress, their perform-ance varied only as a function oftheir mothers’ objective stress.

Project Ice Storm makes aunique contribution to the researchon PNMS. By using a natural disas-ter as the “independent life event”

to which our sample was exposedin a quasi-random fashion, wehave approached the degree of ex-perimental control attained by ani-mal research, permitting us tomake causal conclusions aboutprenatal stress, if somewhat tenta-tively. We have also been able totease apart the relative effects ofobjective exposure and subjectivedistress of the mother. Our resultsalso increase our understanding ofthe moderating effects of the tim-ing of the stressor in gestation,since the onset of this stressor wassudden and unpredictable; the ma-jority of life events, such as thedeath of a loved one or a maritalseparation, tend not to have suchdiscrete onsets. The moderatingeffects of timing seen in this studysuggest that there is no single pe-riod of vulnerability, but that theeffects vary whether the exposureoccurs in the first trimester (headcircumference, cognitive develop-ment at age 2, subclinical autisticsymptoms at age 6), second tri-mester (cognitive and languagedevelopment at age 2 years,fingerprint asymmetry), or thirdtrimester (motor development).The nature of the stressors used inour three PNMS studies will allowus to generalize our results toother independent, sudden onsetevents occurring in pregnancy;however, our use of natural disas-ters will not allow us to generalizeour findings to situations of chronicstress such as poverty or war.The greatest challenge for PNMS

researchers will be to identify themechanisms of action within acomplete biopsychosocial model.The Iowa Flood Study and theQF2011 Study in Australia will aug-ment our ability to test such amodel by providing pre-flood dataon subsamples of women, and byproviding (in QF2011) samples ofplacenta, umbilical cord, and cordblood. These biological sampleswill allow members of our researchgroup to study the cascade ofevents beginning with the mother’sobjective exposure, continuingthrough placenta and umbilicalcord to influence the glucocorti-coid, catecholamine, and immunesystems, and ending in the

284 KING ET AL.


phenotype of the child. We willalso be able to see the moderatingeffects of psychosocial variables,such as family socioeconomic sta-tus, maternal health, and copingstyles. Our research plan alsoincludes extensive analysis ofgene-by-environment interactioneffects and mediation by epigenet-ics and brain development.

Ultimately, the goal of ourresearch program is to increaseunderstanding of the effects ofPNMS and its biopsychosocialmechanisms, such that interven-tions may be developed that opti-mize the overall development ofthe unborn child.

ACKNOWLEDGMENTSThe authors gratefully acknowledgethe generous participation of ProjectIce Storm families since June 1998.Project Ice Storm children wereassessed at age 2 years by ClaudineLeblanc and Veronique Parent, at51=2 by Lorraine Dubois, at age 81=2by Isabelle Bouchard, and at age111=2 by Isabelle Bouchard and Jeni-fer Chapell. The authors wereassisted by Dr. Ross Andersen andhis graduate students, and by HaoZhang during the body compositionand insulin assessments in October2011. Statistical analyses were con-ducted, in part, by Qing Liao, andChunbo Yu. The authors also thankMichael Meaney and his laboratoryfor assaying the salivary cortisolsamples from the initial Project IceStorm evaluation.

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REVIEW Using Natural Disasters to Study the Effects of ... · PNMS research with humans is also limited ... related to developmental windows in gestation. In addition, the researcher