Home Current Issue Previous Issues Published Ahead-of-Print Collections Podcasts For Authors Journal Info
Skip Navigation LinksHome > May 2010 - Volume 72 - Issue 4 > Maternal Psychosocial Adversity During Pregnancy Is Associat...
Text sizing:
A
A
A
Psychosomatic Medicine:
doi: 10.1097/PSY.0b013e3181d2f0b0
Original Articles

Maternal Psychosocial Adversity During Pregnancy Is Associated With Length of Gestation and Offspring Size at Birth: Evidence From a Population-Based Cohort Study

Tegethoff, Marion PhD; Greene, Naomi MPH; Olsen, Jørn MD, PhD; Meyer, Andrea H. PhD; Meinlschmidt, Gunther PhD

Free Access
Article Outline
Collapse Box

Author Information

From the Department of Clinical Psychology and Psychotherapy (M.T., A.H.M., G.M.), Faculty of Psychology, University of Basel, Basel, Switzerland; Department of Neurobehavioral Genetics (M.T.), Institute of Psychobiology, University of Trier, Trier, Germany; Department of Epidemiology (N.G., J.O.), School of Public Health, University of California, Los Angeles, Los Angeles, California; The Danish Epidemiology Science Centre (J.O.), Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark; Department of Applied Statistics in Life Sciences (A.H.M.), Faculty of Psychology, University of Basel, Basel, Switzerland; National Centre of Competence in Research “Swiss Etiological Study of Adjustment and Mental Health (sesam)” (G.M.), Basel, Switzerland.

Address correspondence and reprint requests to Gunther Meinlschmidt, PhD, University of Basel, Birmannsgasse 8, CH-4055 Basel, Switzerland. E-mail: gunther.meinlschmidt@unibas.ch

Received for publication May 10, 2009; revision received December 14, 2009.

The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. This project was financed, in part, by the German National Academic Foundation (PhD scholarship, M.T.), and the Swiss National Science Foundation (SNSF), Project 51A240-104890 (G.M.). The financial supporters had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have not disclosed any potential conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site www.psychosomaticmedicine.org.

Collapse Box

Abstract

Objective: To study in a large-scale cohort with prospective data the associations of psychosocial adversities during pregnancy with length of gestation and offspring size at birth.

Methods: We defined a priori two types of psychosocial adversity during pregnancy: life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). Measures of offspring size at birth, including body weight, body length, abdominal and head circumference, were obtained from a national medical birth registry. We included in the analyses gestational age and offspring size at birth controlled for length of gestation; the latter was calculated by gestational-age-specific z scores (ZS) reported in 10−3. We conducted multiple regression analyses adjusted for potential confounders to estimate the association between exposures and birth outcomes (n = 78017 pregnancies).

Results: Life stress (per score increase by 1; range, 0-18) was associated with shorter length of gestation (days; B, −0.14; 95% confidence interval (CI), −0.19, −0.10), increased offspring body weight (ZS; B, 9.14; 95% CI, 4.99, 13.28), body length (ZS; B, 6.58; 95% CI, 2.39, 10.77), abdominal circumference (ZS; B, 9.96; 95% CI, 5.77, 14.16), and head circumference (ZS; B, 6.13; 95% CI, 1.95, 10.30). Emotional symptoms were associated with shorter length of gestation (days; B, −0.04; 95% CI, −0.07, −0.004) and decreased body length (ZS; B, −4.44; 95% CI, −7.57, −1.32) only.

Conclusions: Life stress and emotional symptoms both predicted a shorter length of gestation, while only life stress predicted an increased offspring size at birth controlled for length of gestation; yet, the associations were rather small. The fetoplacental-maternal unit may regulate fetal growth according to the type of psychosocial adversity and even increase fetal growth in response to maternal stress in major areas of life. This potentially reflects a basic principle of intrauterine human development in response to stress.

BMI = body mass index; DNBC = Danish National Birth Cohort;IL1B = interleukin 1, beta.

Back to Top | Article Outline

INTRODUCTION

Intrauterine growth restriction and preterm delivery are serious complications of pregnancy with increasing rates over the last decades (1). Severe but also mild growth impairment and shortening of gestation are associated with an increased risk of medical problems and death during infancy (2–5). It is also well established that adults who were growth-restricted in utero or born preterm have an increased risk of morbidity and premature mortality from cardiovascular and metabolic disease (6,7). Hence, intrauterine growth restriction and premature birth are of major public health concern, and understanding their causes is recognized as a major research priority (8).

The idea that psychosocial stress during pregnancy influences the developing fetus, with long-term consequences into adult life, has received considerable attention over recent years and has been corroborated on more than one occasion (9). However, the role of prenatal stress in fetal growth remains equivocal. There is evidence that prenatal stress reduces birthweight (10–12), body length (13), head circumference (13,14), and abdominal circumference (15). However, some studies do not support these findings (16,17), and, hence, firm conclusions cannot be drawn. There is also evidence that severe and moderate prenatal stress reduces the length of gestation (10,12,16,18,19), even though contradictory results have also been reported (14,20).

Various forms of maternal psychosocial adversities during pregnancy have been used in previous studies (21), particularly measures of life stress, such as stress at work (22), daily hassles (15), disasters (23), or bereavement (9), and measures of emotional symptoms, such as depression or anxiety (24). The impact of stress resulting from extreme trauma may, however, be different from the impact resulting from more common forms of stress (14), and the impact of emotional symptoms may be different from the impact of life stress (12), given that different types of psychosocial adversities are linked to different biological profiles (25–27). Previous animal data (28) indicated that different types of prenatal stress differentially affect the fetus. However, systematic knowledge on whether specific types of maternal psychosocial adversities during human pregnancy differentially affect the developing fetus is lacking.

Our primary objective was to estimate in a population-based cohort with prospective data, the associations of two a priori defined forms of common maternal psychosocial adversities during pregnancy (29): life stress in terms of perceived burdens in major areas of life (e.g., partnership, work) and self-reported emotional symptoms (e.g., anxiety, nervousness), with length of gestation and offspring size at birth in several tissues.

Back to Top | Article Outline

METHODS

Study Cohort

The present study is based on data of the Danish National Birth Cohort (DNBC) (30). Between 1996 and 2002, the DNBC enrolled 101,042 pregnancies into a nationwide longitudinal study that has permission to follow up the offspring cohort for decades. Participants gave their informed consent, according to the Helsinki II declaration, and the Danish National Committee for Biomedical Research Ethics, Copenhagen, approved the cohort study. We considered as eligible all pregnancies with live singleton births.

Back to Top | Article Outline
Exposures

We obtained information on maternal psychosocial adversities during pregnancy from a computer-assisted interview taken around 30 weeks' gestation. We defined life stress and emotional symptoms as previously described (29). The applied inventory on life stress during pregnancy (interview available at www.bsmb.dk) focuses on burdens in major areas of life, including financial circumstances, housing, work, relationships, pregnancy, and health. Life stress was assessed by nine questions, each covering the time period since the beginning of pregnancy. Answers (no = 0; a little = 1; a lot = 2) were added up into a score (range, 0-18).

The applied inventory on emotional symptoms during pregnancy covers self-reported maternal feelings (e.g., anxiety, nervousness). Items have been selected from the Symptom Checklist-90R (31) and the General Health Questionnaire (32) to cover the most frequent emotional symptoms in adult women. To prevent somatic confounding due to physical conditions during pregnancy, we only included items related to emotional symptoms, but none related to somatic symptoms. Emotional symptoms were assessed by nine questions, each covering the time period since the beginning of pregnancy. Answers (no = 0;a little = 1;a lot = 2) were added up into a score (range, 0-18). Response categories were adjusted to fit the telephone interview conditions. We dealt with up to two missing answers per score by using person-specific mean substitution. Women with more missing answers were excluded. In the analyses, we considered life stress and emotional symptoms as continuous independent variables.

Back to Top | Article Outline
Outcome Measures

We obtained birth outcome measures, such as length of gestation, and anthropometric measures of the offspring at birth, including bodyweight, body length, abdominal circumference, and head circumference, from the Danish National Hospital Register, including the Medical Birth Registry, which is linked to the DNBC database and covers all deliveries of Denmark. The hospital registers provide accurate reporting of obstetric outcome. To account for length of gestation in the anthropometric birth measures we calculated the sex- and gestational age (in days)-specific z scores each anthropometric birth measure (standardized residuals from the regression of each birth measure on gestational age at birth [linear and quadratic terms] separately for males and females of the study sample) (33). We included all birth outcomes as continuous dependent variables.

Back to Top | Article Outline
Statistical Analyses

We performed the descriptive analyses of maternal and infant demographic, anthropometric, and clinical baseline characteristics and analyses of independent and dependent variables by calculating frequencies and percentages of the discrete variables. We calculated means and standard deviations for symmetrically distributed variables and medians and ranges for variables with nonsymmetrical distributions, as distinguished by visual inspection of data plots.

To determine the associations of maternal life stress and emotional symptoms during pregnancy with length of gestation and anthropometric measures of the offspring at birth, we conducted separate linear regression analyses for length of gestation and the gestational age-adjusted z scores of the anthropometric measures obtained at birth. To obtain less biased estimates, we adjusted our models a priori for several well-established predictors of obstetric outcomes that may confound or suppress effects, including socioeconomic status, maternal age, infant sex, parity, maternal prepregnancy body mass index (BMI), occurrence of hypertension and diabetes during pregnancy, and smoking status, with the categories indicated in Table 1. We obtained information on parity, maternal prepregnancy BMI, socioeconomic status, and maternal age at birth from three computer-assisted telephone interviews at approximately 12 weeks' and 30 weeks' gestation and 6 months post partum. The Danish Medical Birth Registry provided information on infant sex.

Table 1
Table 1
Image Tools

We inspected residual plots to verify linearity, normality, and homoscedasticity assumptions and ensured that multicollinearity between covariates was generally low based on variance inflation factors. We excluded 208 outliers in birth outcomes, such as all values lying outside the range of their gestational age-specific mean ± 3 standard deviations according to previously established growth charts (34,35).

In total, 4842 singletons were born to mothers who contributed more than one pregnancy to the study. To correct for possible dependence between birth outcomes in these infants, all standard errors were calculated using the clustered sandwich estimator. We repeated all analyses, including only the first pregnancy of each woman in the cohort to control for previous reproductive experiences and their possible effects on exposures (36).

We report unstandardized (B) regression coefficients, including 95% confidence intervals, standardized (β) regression coefficients, and, for illustrative purposes, p values for each of the predictors (life stress and emotional symptoms). To additionally test whether the regression coefficients of the predictors were robust, we cross-validated each adjusted regression model by using the Chow test: We split the total sample into two random parts, amounting to 75% and 25% of the total sample, and we created a new variable that indicated to which subsample each case belonged. We then computed two interaction terms by multiplying this grouping variable by each of the two predictors. We repeated the separate multiple regression analyses in the total sample, including the grouping variable as well as the interaction terms. A nonsignificant p value of the interaction term indicates that the assumption of no interaction, meaning no difference between the 75% and 25% subsamples, is compatible with data.

All tests were two-tailed and we set the level of significance at .05. We dealt with loss to follow-up and missing data as follows: a) in the exposure scores and outcome variables by restricting analyses to mother-newborn pairs with complete data; and b) in the covariates by including an extra category for those with missing information in the analyses.

For statistical analyses, we used Stata software (version 10.0 SE; Stata Corporation, College Station, Texas).

Back to Top | Article Outline

RESULTS

Study Cohort Descriptives

Of the 101,042 pregnancies initially enrolled in the DNBC (approximately 30% of all Danish births in the study period and 60% of those invited to the study) (30), we considered 92,676 (92%) eligible for participation. Of these, 85,189 mothers (92%) completed the required interview at 30 weeks of gestation. Complete data on maternal stress and birth outcomes were available for 78,017 (92%) of the remaining mother-newborn pairs (Fig. 1). Table 1 gives details on maternal and infant baseline characteristics, including the adversity scores, obstetric outcomes, and covariates under study. The prevalence of low birthweight, defined as a birthweight of <2500 g, and preterm delivery, defined as delivery before 37 completed weeks of gestation, was 1.73% (n = 1348) and 2.92% (n = 2279), respectively.

Figure 1
Figure 1
Image Tools
Back to Top | Article Outline
Multiple Regression Analyses

After adjustment for maternal age, socioeconomic status, infant sex, parity, prepregnancy BMI, hypertension, diabetes, and smoking, higher life stress during pregnancy was associated with a significantly shorter length of gestation and higher z scores of body weight, body length, abdominal and head circumferences of the offspring at birth. After the same adjustment, more emotional symptoms were associated with a significantly shorter length of gestation and lower z scores of the offspring's body length at birth. All other associations were not statistically significant (Table 2). All adjusted models were highly significant (p < .001) but explained only between 1.0% and 8.1% of the variance in the respective birth measures.

Table 2
Table 2
Image Tools

Cross-validation confirmed the stability of the regression coefficients across the two random subsamples (interaction subsample group × predictor: all p > .05). When we repeated adjusted analyses, using only the women's first pregnancies, regression coefficients were of similar magnitude as those presented in Table 2. Estimates of the associations of life stress and emotional symptoms during pregnancy, with anthropometric birth measures not corrected for length of gestation are provided online (Supplemental Digital Content 1, http://links.lww.com/PSYMED/A7).

Back to Top | Article Outline

DISCUSSION

Our main finding was that common maternal life stress and emotional symptoms during pregnancy were associated with a shorter length of gestation. Whereas life stress was associated with an increased offspring size at birth, as indicated by several anthropometric measures, controlled for length of gestation, emotional symptoms were related to reduced body length at birth controlled for length of gestation, but not to any of the other anthropometric birth measures. The magnitude of the associations was rather small. Therefore, the clinical relevance of the findings should be interpreted with caution.

Our results indicate that the fetoplacental-maternal unit may have the potential to specifically regulate fetal growth in response to maternal psychosocial adversities, according to the type of adversity (37). This potentially reflects a basic principle of early human development in response to stress.

Our observation of a slightly reduced length of gestation after life stress and emotional symptoms is in line with several previous studies (10,12,16,18,19) that demonstrated largely consistently that maternal stress during pregnancy reduces the length of gestation. Our findings strengthen the evidence that this effect occurs across the entire range of stress intensities and gestational lengths and is not restricted to extreme stress and extreme premature delivery (38).

The integration of our results on offspring size at birth into the available literature is more challenging. First, our finding of increased offspring size at birth, controlled for length of gestation, after maternal life stress during pregnancy is in contrast to most studies that reported either decreased (14,23) or unchanged (16) fetal growth after maternal stress during pregnancy. Only one other study to date detected that fetuses of pregnant women with moderate life stress grew faster, whereas fetuses of women with severe life stress grew slower in utero, as compared with a reference group (13). It has previously been shown that maternal stress during pregnancy can predict improved fetal and infant development (39) and hypothesized that mild-to-moderate challenge may well act to promote organ maturation (40). One explanation for the inconsistent findings across studies is the difference in definitions of maternal stress, as different stressor characteristics, including type, are linked to different biological profiles (27,28). Hence, different stressor characteristics might differentially affect fetal growth via different biological pathways.

Second, our finding that emotional symptoms during pregnancy were related to reduced body length, controlled for length of gestation, is generally in line with the prevalent notion that prenatal stress reduces fetal growth. However, to the best of our knowledge, only two other groups have studied the association of emotional symptoms with body length at birth. These authors reported that maternal anxiety was not related to body length at birth (17) and that neither maternal anxiety, depression, nor hassle scores were related to fetal femur length (15). One potential explanation for the difference between these and our results is that sample sizes in the previous studies were too small (n <100) to detect rather subtle associations.

Third, except for decreased offspring body length, controlled for length of gestation, after emotional symtoms, we revealed no reduced birth anthropometrics in any other tissue in relation to emotional symptoms. This is in line with several previous studies (16,41) but in contrast to others (10–12,22). One reason for these discrepant findings, besides small sample sizes, retrospective data, or different definitions of maternal stress, may be the inconsistent control for potential confounders (42), including smoking. There is evidence that smoking occurs as a consequence of stress (43), even in pregnant women (44). Therefore, smoking may be an intermediate variable between maternal stress and fetal growth, and its inclusion as potential confounder may lead to an underestimation of the total maternal stress effect. When we repeated analyses without adjustment for smoking, emotional symptoms were related to reduced birth anthropometrics, controlled for length of gestation, in all fetal tissues (data not shown). This relationship indicates that growth-inhibiting effects of emotional symptoms may be largely mediated by smoking, rather than resulting from behavior-independent intrinsic physiological changes that are directly elicited by emotional symptoms (16). Future studies should clarify the role of potential mediators acting on the pathway between maternal stress during pregnancy and obstetric outcomes.

Several biological mechanisms may be proposed as mediators of the putative relationship between maternal stress during pregnancy and obstetric outcomes, provided the associations are causal. Increased concentrations of corticotropin-releasing hormone may play a role in the earlier onset of parturition observed after life stress and emotional symptoms, as corticotropin-releasing hormone has been recognized to determine the timing of parturition (45) and, hence, is a putative physiological mediator bridging maternal stress during pregnancy and reduced length of gestation (46).

We propose that life stress may activate physiological mechanisms that underlie the increase in gestational age-adjusted offspring birth size. The placenta is a key candidate linking maternal life stress and increase in fetal growth. Previous human studies (47,48) suggested that fetal growth depends on placental weight across the entire range of the growth spectrum, and, interestingly, it has been shown that the placenta has the potential for compensatory growth in an adverse intrauterine environment (49). We recently observed that maternal life stress during pregnancy was associated with increased placental growth in human pregnancies (M.T., N.G., J.O., A.H.M., G.M., paper submitted). Another candidate mechanism is fetal insulin, which is increased following stress (50) and promotes energy storage and thereby weight gain and abdominal fat mass.

On a molecular level, preliminary evidence suggested that altered deoxyribonucleic acid methylation in the placenta plays a role in fetal growth (51). However, the role of epigenetic processes in linking prenatal adversities and fetal growth needs further research in humans.

The physiological processes underlying the putative relationship between emotional symptoms and reduced body length at birth, controlled for length of gestation, remain to be elucidated. There is first evidence that, in rats, prenatal exposure to interleukin 1, beta (Human Genome Organization Gene Nomenclature Committee symbol: IL1B) resulted in decreased skeletal growth (52). Elevated stress levels across pregnancy are predictive of increased production of proinflammatory cytokines, including IL1B, in humans (53). These results suggest IL1B as a putative link between prenatal stress and bone growth.

Based on our results, Figure 2 illustrates a tentative model of the putative associations of life stress and emotional symptoms with fetal growth, assuming they are causal.

Figure 2
Figure 2
Image Tools

With regard to the medical relevance of our findings, it should be noted that shorter length of gestation (2,5) and shorter body length at birth (54,55) are associated with infant morbidity and mortality and detrimental health throughout life, including hypertension, cardiovascular disease, insulin resistance, type 2 diabetes, cancer, and premature mortality. Moreover, it has been described that, in infants, rapid weight gain during childhood increases the risk of disease in adulthood (56,57). As we show increased offspring size at birth controlled for length of gestation, after maternal life stress during pregnancy, our results raise the question as to whether the early intrauterine occurrence of “preventive” or “compensatory” growth has similar detrimental consequences as the later “catch-up growth.” Future studies are needed to address the medical relevance of our results, once corroborated.

This study has important strengths. First, we analyzed prospective data from a total of 78,017 mother-newborn pairs, allowing for the detection of even subtle associations. Together with the work of Khashan and colleagues (11), who studied 1.4 million mother-newborn pairs with approximately 25,000 exposed to severe stress, this is the largest study on the topic, with a focus on common stress variations. Second, the data set was linked to a comprehensive medical birth registry, providing information that we expect to be without systematic measurement errors. Third, we included a broad range of birth outcome measures. Fourth, we used a definition of prenatal adversities with a focus on everyday occurrence (rather than rare disasters). This has major relevance within the general population. Fifth, we were able to adjust our analyses for a number of major potential confounders, including maternal age, socioeconomic status, infant sex, parity, prepregnancy BMI, occurrence of hypertension and diabetes during pregnancy, and smoking status. Therefore, we believe it is unlikely that residual confounding has biased our results, but our findings need to be corroborated in an independent data set. Furthermore, by including both exposures, life stress and emotional symptoms, into one model, we controlled the association of each exposure variable with the outcomes for the other exposure variable respectively, taking into account the modest association between the two exposures. Finally, we verified the stability of our results by cross-validation and repeated all analyses including only the first pregnancy of each woman in the cohort to control for previous reproductive experiences (36), which resulted in no relevant change in the estimates.

There are also limitations to this study. First, we did not have data on the timing of stress exposure, which has been discussed to play a role in the relationship between maternal stress and obstetric outcome, with inconsistent results (11,58). However, both life stress and emotional symptoms during pregnancy most likely reflect rather chronic states of adversities, which are often impossible to time precisely, and were probably present during a substantial part of pregnancy. Second, we used information on offspring anthropometrics at birth, controlling for length of gestation by calculating gestational-age adjusted z scores (33), but we did not have data on growth rates for specific time periods of gestation. To obtain more detailed data on the association between maternal stress and fetal growth trajectory, future studies should use repeated gestational ultrasound measures at short time intervals, which are, however, almost impossible within a population-based cohort. Finally, we did not have biological markers for maternal stress, in addition to information from self-reports, which would help in future studies to elucidate underlying physiological mechanisms of the putative prenatal stress effects; however, it is hardly feasible to have biological samples from such a large cohort.

Of all eligible mother-newborn pairs, 92% participated in the required interview, and of these, we included 92% in our analyses. Those excluded mostly had missing data on maternal stress or obstetric outcomes. However, on the basis of the good retention rate and the high percentage of complete data, we think it is unlikely that, unless the association between maternal stress and obstetric outcomes differs considerably between the study sample and those lost, loss of mother-newborn pairs has introduced relevant bias.

The interview in which information on maternal stress was assessed was taken between 6 months and 7 months of gestation; no information on maternal stress was available for those pregnancies that terminated before the interview; hence, these mother-newborn pairs were excluded from our analyses. Consequently, we have limited data on extreme preterm births, which is also reflected by the rather low prevalence of preterm delivery and low birthweight.

Future studies are needed to corroborate the findings and to learn about the underlying physiological mechanisms and clinical relevance of the observed associations and to reveal changeable factors within these relationships to establish useful prevention and intervention approaches, if necessary. It should be noted that the identified associations were rather small. For example, the length of gestation was reduced by 0.14 days, that is approximately 3 hours, per increase of the life stress score by one, or reduced by 2.24 days, assuming a maximum increase in the life stress score. Therefore, life stress alone is unlikely to lead to preterm birth. However, given the estimated relationship is causal, it may contribute to a clinically relevant reduction of the length of gestation in pregnancies threatened by other risk factors. It has been hypothesized that also subtle alterations in obstetric outcomes may increase susceptibility to disease in later life (59). However, this needs to be investigated in large follow-up studies.

In this large cohort, life stress and emotional symptoms during pregnancy were both related to a shorter length of gestation, while they were differentially associated with birth size, controlled for length of gestation. Life stress was related to an increased offspring size at birth in several tissues, whereas emotional symptoms were related to reduced body length at birth. The results indicate that the fetoplacental-maternal unit may have the potential to regulate fetal growth according to the type of maternal adversity during pregnancy. This potentially reflects a basic principle of early human development in response to stress. Our results may contribute to a better understanding of intrauterine processes in response to stress.

Back to Top | Article Outline

REFERENCES

1. Martin JA, Kung HC, Mathews TJ, Hoyert DL, Strobino DM, Guyer B, Sutton SR. Annual summary of vital statistics: 2006. Pediatrics 2008;121:788–801.

2. Kramer MS, Demissie K, Yang H, Platt RW, Sauvé R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA 2000;284:843–9.

3. McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 1985;312:82–90.

4. McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999;340:1234–8.

5. Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics 2004;114:372–6.

6. Barker DJ, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993;306:422–6.

7. Hofman PL, Regan F, Jackson WE, Jefferies C, Knight DB, Robinson EM, Cutfield WS. Premature birth and later insulin resistance. N Engl J Med 2004;351:2179–86.

8. World Health Organization. Promoting Optimal Fetal Development: Report of a Technical Consultation. Geneva: World Health Organization; 2006.

9. Khashan AS, Abel KM, McNamee R, Pedersen MG, Webb RT, Baker PN, Kenny LC, Mortensen PB. Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry 2008;65:146–52.

10. Copper RL, Goldenberg RL, Das A, Elder N, Swain M, Norman G, Ramsey R, Cotroneo P, Collins BA, Johnson F, Jones P, Meier AM. The preterm prediction study: maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1996;175:1286–92.

11. Khashan AS, McNamee R, Abel KM, Pedersen MG, Webb RT, Kenny LC, Mortensen PB, Baker PN. Reduced infant birthweight consequent upon maternal exposure to severe life events. Psychosom Med 2008;70:688–94.

12. Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C, Garite TJ. The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol 1993;169:858–65.

13. Lederman SA, Rauh V, Weiss L, Stein JL, Hoepner LA, Becker M, Perera FP. The effects of the World Trade Center event on birth outcomes among term deliveries at three lower Manhattan hospitals. Environ Health Perspect 2004;112:1772–8.

14. Engel SM, Berkowitz GS, Wolff MS, Yehuda R. Psychological trauma associated with the World Trade Center attacks and its effect on pregnancy outcome. Paediatr Perinat Epidemiol 2005;19:334–41.

15. Diego MA, Jones NA, Field T, Hernandez-Reif M, Schanberg S, Kuhn C, Gonzalez-Garcia A. Maternal psychological distress, prenatal cortisol, and fetal weight. Psychosom Med 2006;68:747–53.

16. Peacock JL, Bland JM, Anderson HR. Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine. BMJ 1995;311:531–5.

17. Sjostrom K, Valentin L, Thelin T, Marsal K. Maternal anxiety in late pregnancy and fetal hemodynamics. Eur J Obstet Gynecol Reprod Biol 1997;74:149–55.

18. Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P. Maternal stress and preterm birth. Am J Epidemiol 2003;157:14–24.

19. Hedegaard M, Henriksen TB, Sabroe S, Secher NJ. Psychological distress in pregnancy and preterm delivery. BMJ 1993;307:234–9.

20. Rich-Edwards JW, Kleinman KP, Strong EF, Oken E, Gillman MW. Preterm delivery in Boston before and after September 11th, 2001. Epidemiology 2005;16:323–7.

21. Beydoun H, Saftlas AF. Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence. Paediatr Perinat Epidemiol 2008;22:438–66.

22. Oths KS, Dunn LL, Palmer NS. A prospective study of psychosocial job strain and birth outcomes. Epidemiology 2001;12:744–6.

23. Berkowitz GS, Wolff MS, Janevic TM, Holzman IR, Yehuda R, Landrigan PJ. The World Trade Center disaster and intrauterine growth restriction. JAMA 2003;290:595–6.

24. Andersson L, Sundstrom-Poromaa I, Wulff M, Astrom M, Bixo M. Neonatal outcome following maternal antenatal depression and anxiety: a population-based study. Am J Epidemiol 2004;159:872–81.

25. Adell A, Casanovas JM, Artigas F. Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas. Neuropharmacology 1997;36:735–41.

26. Kioukia-Fougia N, Antoniou K, Bekris S, Liapi C, Christofidis I, Papadopoulou-Daifoti Z. The effects of stress exposure on the hypothalamic-pituitary-adrenal axis, thymus, thyroid hormones and glucose levels. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:823–30.

27. Pacak K, Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev 2001;22:502–48.

28. Richardson HN, Zorrilla EP, Mandyam CD, Rivier CL. Exposure to repetitive versus varied stress during prenatal development generates two distinct anxiogenic and neuroendocrine profiles in adulthood. Endocrinology 2006;147:2506–17.

29. Sondergaard C, Olsen J, Friis-Hasche E, Dirdal M, Thrane N, Sorensen HT. Psychosocial distress during pregnancy and the risk of infantile colic: a follow-up study. Acta Paediatr 2003;92:811–6.

30. Olsen J, Melbye M, Olsen SF, Sørensen TI, Aaby P, Andersen AM, Taxbøl D, Hansen KD, Juhl M, Schow TB, Sørensen HT, Andresen J, Mortensen EL, Olesen AW, Søndergaard C. The Danish National Birth Cohort—its background, structure and aim. Scand J Public Health 2001;29:300–7.

31. Derogatis LR. SCL-90: Administration, Scoring, and Procedures Manual-1. for the R(evised) Version. Baltimore: Johns Hopkins University Press;1977.

32. Goldberg D. The Detection of Psychiatric Illness by Questionnaire. London: Oxford University Press;1972.

33. Leon DA, Lithell HO, Vagero D, Koupilova I, Mohsen R, Berglund L, Lithell UB, McKeigue PM. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29. BMJ 1998;317:241–5.

34. Figueras F, Torrents M, Munoz A, Comas C, Antolin E, Echevarria M, Mallafre J, Carrera JM. References intervals for fetal biometrical parameters. Eur J Obstet Gynecol Reprod Biol 2002;105:25–30.

35. Niklasson A, Albertsson-Wikland K. Continuous growth reference from 24th week of gestation to 24 months by gender. BMC Pediatr 2008;8:8.

36. Olsen J. Confounding by exposure history and prior outcome. Epidemiology 2008;19:635–6;author reply, 636.

37. Worthman CM, Kuzara J. Life history and the early origins of health differentials. Am J Hum Biol 2005;17:95–112.

38. Wadhwa PD. Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology 2005;30:724–43.

39. DiPietro JA, Novak MF, Costigan KA, Atella LD, Reusing SP. Maternal psychological distress during pregnancy in relation to child development at age two. Child Dev 2006;77:573–87.

40. Huether G. Stress and the adaptive self-organization of neuronal connectivity during early childhood. Int J Dev Neurosci 1998;16:297–306.

41. Stein A, Campbell EA, Day A, McPherson K, Cooper PJ. Social adversity, low birth weight, and preterm delivery. BMJ 1987;295:291–3.

42. Lobel M. Conceptualizations, measurement, and effects of prenatal maternal stress on birth outcomes. J Behav Med 1994;17:225–72.

43. Kouvonen A, Kivimäki M, Virtanen M, Pentti J, Vahtera J. Work stress, smoking status, and smoking intensity: an observational study of 46,190 employees. J Epidemiol Community Health 2005;59:63–9.

44. Floyd RL, Rimer BK, Giovino GA, Mullen PD, Sullivan SE. A review of smoking in pregnancy: effects on pregnancy outcomes and cessation efforts. Annu Rev Public Health 1993;14:379–411.

45. McLean M, Bisits A, Davies J, Woods R, Lowry P, Smith R. A placental clock controlling the length of human pregnancy. Nat Med 1995;1:460–3.

46. Wadhwa PD, Culhane JF, Rauh V, Barve SS. Stress and preterm birth: neuroendocrine, immune/inflammatory, and vascular mechanisms. Matern Child Health J 2001;5:119–25.

47. Hafner E, Metzenbauer M, Hofinger D, Munkel M, Gassner R, Schuchter K, Dillinger-Paller B, Philipp K. Placental growth from the first to the second trimester of pregnancy in SGA-foetuses and pre-eclamptic pregnancies compared to normal foetuses. Placenta 2003;24:336–42.

48. Taricco E, Radaelli T, Nobile de Santis MS, Cetin I. Foetal and placental weights in relation to maternal characteristics in gestational diabetes. Placenta 2003;24:343–7.

49. Hindmarsh PC, Geary MP, Rodeck CH, Jackson MR, Kingdom JC. Effect of early maternal iron stores on placental weight and structure. Lancet 2000;356:719–23.

50. Marchini G, Hagenas L, Kocoska-Maras L, Berggren V, Hansson LO. Insulin-like growth factor binding protein-1 and interleukin-6 are markers of fetal stress during parturition at term gestation. J Pediatr Endocrinol Metab 2005;18:777–83.

51. Guo L, Choufani S, Ferreira J, Smith A, Chitayat D, Shuman C, Uxa R, Keating S, Kingdom J, Weksberg R. Altered gene expression and methylation of the human chromosome 11 imprinted region in small for gestational age (SGA) placentae. Dev Biol 2008;320:79–91.

52. Swolin-Eide D, Nilsson C, Holmang A, Ohlsson C. Prenatal exposure to IL-1beta results in disturbed skeletal growth in adult rat offspring. Pediatr Res 2004;55:598–603.

53. Coussons-Read ME, Okun ML, Nettles CD. Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy. Brain Behav Immun 2007;21:343–50.

54. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med 2000;133:176–82.

55. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ. Fetal growth and coronary heart disease in south India. Lancet 1996;348:1269–73.

56. Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJ. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 1999;318:427–31.

57. Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 2000;320:967–71.

58. Hedegaard M, Henriksen TB, Secher NJ, Hatch MC, Sabroe S. Do stressful life events affect duration of gestation and risk of preterm delivery? Epidemiology 1996;7:339–45.

59. Gluckman PD, Hanson MA, Beedle AS. Early life events and their consequences for later disease: a life history and evolutionary perspective. Am J Hum Biol 2007;19:1–19.

Keywords:

fetal development; gestational age; intrauterine exposure; pregnancy; prenatal programming; prenatal stress

Supplemental Digital Content

Back to Top | Article Outline

Copyright © 2010 by American Psychosomatic Society

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.