DEPRESSION AND ANXIETY 17:152–161 (2003)

Research Article
DEPRESSIVE SYMPTOMS AT TWO MONTHS AFTER
MISCARRIAGE: INTERPRETING STUDY FINDINGS FROM
AN EPIDEMIOLOGICAL VERSUS CLINICAL PERSPECTIVE
Richard Neugebauer, Ph.D., M.P.H.n

We identify two study designs used to investigate psychiatric symptoms following

reproductive loss. One design examines psychiatric outcomes in a single cohort of
bereaved women; the other compares psychiatric outcomes in bereaved and non-
bereaved cohorts. We employ the findings from one study of depressive symptoms
following miscarriage to exemplify these designs and inferential differences in
causal inferences that can be drawn. We interviewed a cohort of 114 women at
6–8 weeks after miscarriage and a cohort of 318 community women not recently
pregnant. Depressive symptoms were assessed with the Center for Epidemiologic
Studies Depression (CES-D) Scale. Among miscarrying women, the mean level
of depressive symptoms was substantially elevated above that in the community
cohort (adjusted difference in means between cohorts, 4.9, 95% confidence
interval [CI] 2.3–7.4). Among miscarrying women, 20.2% were highly
symptomatic (CES-D 30þ), as compared with 10.1% among community
women (adjusted odds ratio [OR] 2.8, 95% CI 1.4–5.6). However, in contrast to
findings from the same study concerning depressive reactions at 2 weeks after
loss, the impact of miscarriage on depressive symptoms at 6–8 weeks was
markedly greater for younger women and possibly for women with a history of
prior reproductive loss, but otherwise did not vary with number of living
children, marital status, ethnicity or educational level. We conclude that
miscarrying women first seen at their 6- to 8-week post miscarriage gynecologic
visit are likely to be more depressed on average than otherwise comparable
women who have not experienced a recent reproductive loss. Factors that
moderate the impact of miscarriage may vary with time since loss. Enhanced
recognition of the implications of study design for research inferences may help
bring greater clarify and uniformity to findings from future investigations in
this field. Depression and Anxiety 17:152–161, 2003. & 2003 Wiley-Liss, Inc.

Key words: spontaneous abortion; miscarriage; depression; pregnancy; epide-

miology; stillbirth; neonatal death

Epidemiology of Developmental Brain Disorders Department,
New York State Psychiatric Institute, New York, NY, and
Gertrude H. Sergievsky Center, Faculty of Medicine, Columbia
University, New York, NY.
n
Correspondence to: Richard Neugebauer, Ph.D., M.P.H., Box
53, Epidemiology of Developmental Brain Disorders Department,
NYS Psychiatric Institute, New York, NY 10032.
E-mail: RN3@columbia.edu

Received for publication 16 November 2001; Revised 26 Novem-

ber 2001; Accepted 27 November 2002
Contract grant sponsor: National Institutes of Health,
Bethesda; Contract grant numbers: MH39581, HD15509, Published online in Wiley InterScience (www.interscience.wiley.
HD12207. com). DOI 10.1002.da.10019

& 2003 WILEY-LISS, INC.

 Research Article: Depression and Reproductive Loss
INTRODUCTION
Miscarriage is the most frequent complication of
pregnancy with 10–20% of clinically recognized
pregnancies ending in a miscarriage [Kline et al.,
1989]. In the United States, for example, approximately
half a million women miscarry each year [National
Center for Health Statistics, 1995]. Miscarriage repre-
sents a complex biological and psychological event. It
constitutes the end of a pregnancy and, for many
women, the loss of a wanted and deeply desired future
child. Simultaneously, it can engender persistent
doubts about procreative competence. Miscarriage
may also be accompanied by considerable physical
pain and the potentially disturbing sight of blood and
tissue. For these reasons, miscarrying women are likely
to experience depressive reactions as well as an increase
in anxiety symptoms in the aftermath of their loss.
Thus, frequency of miscarriage and the likelihood of it
af fecting mental health adversely makes assessment of
its psychological impact an important clinical and
epidemiologic, public health question.
Over the past three decades, numerous studies have
investigated psychiatric symptoms and disorders, prin-
cipally depression and anxiety, among women experi-
encing reproductive loss, with the form of bereavement
ranging from early miscarriage to stillbirth and
neonatal death [Benfield et al., 1978; Beutel et al.,
1995; Clarke and Williams, 1979; Cordle and Pretty-
man, 1994; Forrest et al., 1982; Friedman and Gath,
1989; Garel et al., 1992; Geller et al., 2001; Graham
et al., 1987; Jannsen et al., 1996; Kennel et al., 1970;
Klier et al., 2000; La Roche et al., 1984; Lee et al.,
1997; Neugebauer et al, 1992a, b, 1997; Nicol et al.,
1986; Nikcevic et al., 1999; Peppers and Knapp, 1980;
Robinson et al., 1994; Rowe et al., 1978; Seibel and
Graves, 1980; Slade, 1994; Stirtzinger et al., 1999;
Swanson, 2000; Thaper and Thaper, 1992; Tudehope
et al., 1986]. However, confident inferences from these
studies are often compromised by small sample sizes,
thereby precluding statistical adjustment for potentially
confounding variables and raising questions as to the
generalizability of the findings. Additionally, within a
given study, scheduling of subject assessments some-
times extends over many weeks or even over several
months after loss. As a consequence, results can not
easily inform clinical practice because they do not apply
to any particular point in time after bereavement, for
example, the interval when the first postmiscarriage
gynecologic visits are typically scheduled.
Finally, although these studies are often grouped
together in reviews [Slade, 1994], they fall into two
fundamentally different categories based on their
design and corresponding inferential strengths. The
first design involves one group of bereaved women and
entails assessment of their symptom levels or rates of
disorder following loss. The second design involves at
least two groups of women, one reporting reproductive
loss, the others not, and entails comparison of
153
depressive symptoms or rates of disorder in the two
groups of women.
Examination of symptom levels just in a bereaved
cohort (feasible with either of the two study types
described) conveys the magnitude of psychiatric
disturbance after loss, thereby potentially sensitizing
clinicians and the lay public to the emotional needs of
these patients. Allocation of additional mental health
resources might ensue. Further, these studies can draw
attention to special subgroups of patients, for example,
childless miscarrying women whose symptom levels
may be particularly elevated relative to other miscarry-
ing women.
However, single cohorts are not informative regard-
ing the magnitude of the effect of miscarriage on
psychiatric disturbance. Evaluation of whether the
observed symptom level or rate of disorder among
women with reproductive loss exceeds expected rates
requires a comparison group of non-bereaved indivi-
duals. Without such a comparison group, inferences
about the mental health effects exerted by miscarriages
are hazardous at best.
While this function of comparison groups, so-called
‘‘control groups,’’ is generally recognized, the need for
a comparison cohort to identify factors that ameliorate
or exacerbate the impact of reproductive loss is perhaps
less apparent. Two examples will clarify this point.
Some studies of single bereaved cohorts report that
parous and nulliparous miscarrying women do not
differ on depressive symptom levels [Friedman and
Gath, 1989]. However, to conclude from this finding
that children do not buffer miscarrying women against
depressive reactions to loss is unwarranted. If non-
bereaved parous women are generally more depressed
than non-bereaved nulliparous women, then the
evidence just cited points to a protective effect for
parity following reproductive loss.
Similarly, a number of studies using a single bereaved
cohort report no association between length of gesta-
tion at time of loss and depressive symptom levels
[Peppers and Knapp, 1980]. The inference drawn is
that early and late loss exert an equal impact on
depressive symptoms. Again, such an inference is
erroneous because the study design does not inform
us about depressive symptom levels expected at
different points in gestation in an ongoing pregnancy.
If depressive symptoms typically decline with advan-
cing gestation, then the finding demonstrates that later
loss exerts a disproportionately greater depressive
effect on miscarrying women [Neugebauer et al.,
1992b]. Without knowledge of expected levels of
symptoms among unexposed individuals, we cannot
identify factors that diminish or intensify the impact of
bereavement.
The inability of single-cohort studies to estimate the
effect of loss on depressive symptom levels and to
identify factors that moderate this ef fect passes largely
unnoticed in the bereavement literature. Here, we
report results from a study of depressive reactions to
154 Neugebauer
miscarriage that used two cohorts, one exposed, the
other unexposed, to recent reproductive loss. By
presenting within-cohort and across-cohort analyses
based on the same study with their corresponding
interpretations, we hope to clarify further the contrast-
ing inferences to which each analysis gives rise.
In two previous papers, we investigated whether and
under what conditions miscarriage was associated with
an increase in depressive symptoms (at 2 weeks after
loss) and risk for an episode of major depressive
disorder in the 6 months after loss [Neugebauer et al.,
1997]. Here, we report on overall symptom levels and
factors potentially moderating the impact of miscar-
riage on depressive symptoms among women first
assessed in the second month (weeks 6–8) after loss.
This group has not been previously analyzed or
described in detail elsewhere.
Of our reports published to date, these results have
the most immediate potential relevance for clinical
practice because they provide estimates of depressive
symptoms around the time that women are first seen by
their gynecologist after their miscarriage. This analysis
af fords an opportunity to examine the level of
depressive symptoms in the second month after loss
and to explore whether protective factors operating at
2 weeks remain ameliorative at 6–8 weeks and are
joined or replaced by others.
At the outset of our investigation, we hypothesized a
priori that miscarrying women would exhibit elevated
depressive symptoms, relative to a companion group,
for several months after loss. We also hypothesized that
the effect of miscarriage on depressive symptoms
would be more pronounced among childless women,
women with prior reproductive losses and with older
women, in particular, among women over age 34.
These a priori hypotheses were retained in the current
series of analyses despite having received only partial
support from our previous results. We test these
hypotheses by comparing depressive symptom levels
among miscarrying women first assessed at 6–8 weeks
after loss with those among women selected from the
same community but free of recent reproductive loss.
We found that 2 weeks after loss, miscarrying
women experienced substantially elevated depressive
symptom levels as compared with community women.
Specifically, among miscarrying women, the propor-
tion highly symptomatic was more than four times that
in a cohort of community women. The effect of
miscarriage on depressive symptoms was disproportio-
nately great for childless women but not so for
miscarrying women with prior losses nor for any
particular age group [Neugebauer et al., 1992b].
SUBJECTS AND METHODS
STUDY DESIGN
The larger study from which the current data are
drawn comprised three cohorts: miscarrying women,
currently pregnant women, and women selected from
the same community as the miscarrying women but
who had not been pregnant in the year preceding
interview. The pregnant cohort estimated depressive
symptom levels expected in an uninterrupted preg-
nancy, thereby approximating the levels among mis-
carrying women immediately prior to loss.
Accordingly, the pregnant cohort is excluded from
the current analyses focused on symptoms present at
least 6 weeks after loss. The community cohort
afforded an estimate of the level of depressive
symptoms in the absence of any recent reproductive
event. The community cohort serves as the sole
comparison cohort in the present analyses.
MISCARRIAGE COHORT
Miscarriage was defined as the involuntary termina-
tion of a nonviable intrauterine pregnancy before 28
completed weeks of gestation with the conceptus dead
on expulsion. Miscarrying women were derived from
cases participating in an antecedent hospital-based case
control study of risk factors for miscarriage [Kline
et al., 1991a,b]. This prior case control investigation
interviewed 81% of all identified cases (i.e., miscarry-
ing women) attending a New York City hospital from
late in 1984 to 1986. Interviewed and uninterviewed
cases were distributed similarly on sociodemographic
and reproductive characteristics [Neugebauer et al.,
1992a,b].
At the conclusion of the case control interview, all
cases 18 years of age or older, English- or Spanish-
speaking, and available by telephone, were invited to
enter the current cohort study. We aimed to evaluate
these miscarrying women at three time points: 2 weeks
after miscarriage, 6–8 weeks, and 26–35 weeks
(6 months). Overall, 73% (n ¼ 382) of eligible mis-
carrying women were assessed on at least one occasion:
232 women were first interviewed at 2 weeks, 114 were
first interviewed at 6–8 weeks, 36 at 26–35 weeks. This
unintended staggered recruitment was the consequence
of logistical challenges associated with relocating
subjects after their departure from the hospital.
Interviewing of miscarrying women concluded in 1987.
The current report examines depressive symptom
levels among miscarrying women first interviewed at
6 weeks after loss. In addition to the 114 women first
interviewed at 6–8 weeks after loss, 196 women already
assessed at 2 weeks after loss were reinterviewed. The
women being reinterviewed no longer evidenced
elevated depressive symptom levels. We have offered
detailed evidence elsewhere indicating that this symp-
tom decline was the likely consequence of an unin-
tended therapeutic effect of the initial study interview
[Neugebauer et al., 1992b]. The initial interview lasted
between 1 and 2 hours and contained elements in
common with grief counseling. We infer that women
first interviewed at 6–8 weeks are likely to provide less
biased estimates of the impact of miscarriage in the
 Research Article: Depression and Reproductive Loss 155

second month after loss than the reinterviewed women TABLE 1. Selected sociodemographic and reproductive
[Neugebauer et al., 1992a]. history characteristics among miscarrying women first
interviewed 6–8 weeks after loss and among community
womenw
COMMUNITY COHORT
Community women were located by means of Cohort
random-digit dialing of telephone numbers. Recruits Characteristic Miscarriage Community
were residentially stratified by the area codes and (n ¼ 114) (n ¼ 318)
exchanges of the interviewed miscarrying women. A
Age, mean (sd ), yr 29.2 (6.1) 30.0 (6.4)
screening interview evaluated whether a potentially
Ethnicity (%)
eligible community woman, a woman aged 18 to 44 Caucasian 44.7 36.6
years, not pregnant in the preceding 12 months, African-American 18.4 19.5
resided at that location. (Eligibility status was estab- Hispanic 28.9 38.2
lished for 92% of the working telephone numbers Other 7.9 5.7
dialed.) Community women were frequency matched Interviewed in Spanish (%) 29.8 26.4
to the miscarrying women on age (in 5-year intervals), Education, yr (%)
language, education (four categories: less than high oHigh school 26.3 20.3
school, high school graduate, college graduate, post- High-school graduate 18.4 24.5
graduate training), and season of interview. (Ethnicity Some college 21.9 29.7
College graduate 33.3 25.5
was recorded but was not used as a matching variable.)
Marital status (%)***
Among known eligible community women, 82% Currently single 28.1 46.5
(n ¼ 318) were interviewed. Community interviews Married 64.0 35.2
were conducted in 1986–1987. Other 7.9 18.3
Nulliparous (%)** 35.1 50.5
Living children, n (%)***
COMPARABILITY OF INTERVIEWED AND 0 36.0 50.5
UNINTERVIEWED STUDY ELIGIBLE 1 41.2 15.7
WOMEN 2 11.4 19.7
3+ 11.4 14.1
Within each cohort, interviewed and uninterviewed
Prior reproductive losses, n (%)a,*
women were similar in age, ethnicity, education, 0 71.1 82.5
language, and season of interview. In the second half 1 21.1 12.9
of the investigation, depressed mood was assessed at 2+ 7.9 4.6
baseline irrespective of a woman’s decision to enter the w
cohort study proper. (For the miscarrying women, Note. Differences between cohorts were assessed using an overall w2
test for categorical variables and by a one-way analysis of variance for
assessment of mood formed part of the case control
continuous variables.
interview; for the community women, part of the a
Includes spontaneous abortions (86%), fetal deaths (14%).
telephone screening interview.) Interviewed and unin- *Po.05; ** Po.01; *** Po.001.
terviewed women within the initial miscarriage and
community cohorts did not dif fer on levels of
depressed mood.
All subjects gave informed consent to participate
Within the miscarriage cohort, the distribution of
after receiving an explanation of study procedures. The
women first interviewed at 6–8 weeks (Table 1) and of
study was approved by the Institutional Review Board
the remaining miscarrying women interviewed in the
of Columbia Presbyterian Medical Center and of New
study was similar on age, language of interview, marital
York State Psychiatric Institute, New York, NY.
status, nulliparity, number of prior losses, and length of
gestation at loss. However, the antecedent case control
study gave priority to interviewing public (as compared
with private) patients, since the former were more
STUDY MEASURES
dif ficult to reach after hospital discharge. Conse- Depressive symptoms were measured using the
quently, women who were White and college graduates Center for Epidemiologic Studies Depression (CES-
were overrepresented among women first interviewed D) Scale, [Radloff, 1977], a 20-item checklist that
at 6–8 weeks. Nonetheless, the level of depressed inquires about the presence and frequency of depres-
mood, measured at baseline, among the women first sive symptoms in the 7 days preceding interview. The
interviewed at 6–8 weeks after loss and the remaining CES-D assesses af fective and somatic aspects of
interviewed miscarrying women did not differ after depressive symptomatology and low self-esteem. Scale
adjustment for these sociodemographic differences. items present a fixed, alternative-choice format for
These results suggest that at baseline the af fective state subjects’ responses regarding symptom frequency,
of women first interviewed at 6–8 weeks after loss was scored from 0 (‘‘rarely’’) to 3 (‘‘most of the time’’).
generally representative of the miscarriage cohort. The CES-D correlates highly with those of other self-
156 Neugebauer
report depressive symptom measures, distinguishes
clinically depressed patients from person in the general
population [Myers and Weissman, 1980; Weissman et
al., 1977], and has been employed previously to
measure depressive symptoms among OB/GYN pa-
tients. [Zuckerman et al., 1989]. Internal consistency
reliabilities (Cronbach’s alpha) of the CES-D in the
two study cohorts overall and in educational, language,
and ethnic subgroups within each cohort are excellent
(.83–.92). Among women in the community cohort,
CES-D scores are inversely associated with socio-
economic status indicators, e.g., educational level, and
directly associated with number of children. These
patterns are consistent with the descriptive epidemiol-
ogy of depressive symptoms, thereby affording evi-
dence of the scale’s construct validity in this study
sample.
STUDY PROCEDURES
Administration of the CES-D, together with the
remainder of the interview covering reproductive
history and sociodemographic data, was by telephone.
The general comparability of sociodemographic, psy-
chiatric symptom, and medical history data secured by
telephone and in-person interviews is well documented
[Aneshensel et al., 1982; Hochstim, 1967; Leimbach,
1982].
The content of the interview with the miscarrying
women precluded the interviewers from being blind to
the exposure status of study subjects. However, efforts
were made to minimize possible interviewer ef fects on
subjects’ responses by the deployment of fully struc-
tured questionnaires and monthly training sessions
proscribing ad hoc interviewer probes and rewording
of interview items. Compliance with these strictures
was confirmed via periodic auditing of taped interviews
by the project director and principal investigator
(R.N.).
ANALYTIC STRATEGY
CES-D scores are presented as symptom means for
the two study cohorts and as the proportion of women
who were highly symptomatic. Women were classified
as highly symptomatic if they scored 30 or above on the
CES-D, corresponding to their endorsing of at least
half of the 20 depressive symptoms ‘‘most of the time’’
for the past week. Analyses using this cut-point,
presented in the form of the odds ratio, assess whether
results pertaining to the entire range of symptom
scores also hold for extreme symptom levels. Approxi-
mately two-thirds of women classified as highly
symptomatic on this basis would be expected to meet
diagnostic criteria for major depressive disorder [Boyd
et al., 1982].
First, we present the distribution of each cohort by
key sociodemographic and reproductive history char-
acteristics (Table 1). Second, for descriptive purposes,
we report the observed CES-D means for each cohort
by the same key sociodemographic and reproductive
history characteristics (see Table 2). Comparison of
observed CES-D means within each cohort is per-
formed using one-way analysis of variance. Third, we
compare differences in overall means between the
miscarriage and community cohort and compute the
ratio of the odds of being highly symptomatic among
miscarrying women to the odds among community
women using ordinary least-squares multiple regres-
sion and maximum likelihood logistic regression,
respectively, to permit adjustment for potentially
confounding variables.
In previous analyses, candidate variables for these
adjusted analyses derived from an a priori list of
potential confounding variables (e.g., marital status)
and moderator variables (e.g., number of children).
Additionally, we screened the data set itself for any
remaining variables warranting analytic control. (The
matching variables used in accruing the community
cohort were also introduced as covariates, both as main
effects and as all possible two-way interaction effects.
These terms did not appreciably influence the regres-
sion coefficients of interest. Consequently, for parsi-
mony, they are omitted from the models presented
here.) To eliminate possible concerns that a different
choice of covariates might explain variations in results
across study time intervals as well as to facilitate direct
comparisons of effect sizes across time points, we
retain here the covariates used previously [Neugebauer
et al., 1992b]. No other sociodemographic or repro-
ductive history variables required analytic control in
this data set. Accordingly, the regression equations
comparing the two cohorts contained the following
terms: maternal age (linear), ethnicity, marital status,
number of children, prior reproductive loss, and
socioeconomic status (using a standardized index that
assigns equal weight to family income and maternal
education). Findings from the least-squares regression
analyses are presented as differences in adjusted means
between the two cohorts; findings from the logistic
regression analyses are presented as adjusted odds
ratios (Table 3). The a priori hypotheses regarding the
possible role of number of children, history of prior
loss, and maternal age as modifiers of the effect of
miscarriage on depressive symptoms were tested with
first-order interaction terms in the regression analyses.
Similar post-hoc exploratory tests of interaction were
performed for ethnicity, educational level, and marital
status. Statistical significance was set at Po.05, two-
tailed, except for interaction terms. Interaction terms
were judged statistically significant at Po.10. No
correction factor was employed for multiple compar-
isons, since the tests regarding the role of number of
children, maternal age, and prior losses as ef fect
modifiers were based on individual a priori hypotheses,
whereas the examination of ethnicity, educational level,
and martial status in the same regard are all expressly
presented as exploratory in nature.
 Research Article: Depression and Reproductive Loss 157

TABLE 2. CES-D scores among miscarrying women first Since the miscarriage cohort was accrued necessarily
interviewed at 6–8 weeks after loss and among community from women who had been reproductively active,
women overall and by selected sociodemographic and a greater proportion of miscarrying women were
reproductive history characteristicsw married, had children, and reported prior losses as
compared with community women (Table 1). The
Cohort regression analyses adjust adequately for the possible
Characteristic Miscarriage Community contribution of these sociodemographic and reproduc-
(n ¼ 114) (n ¼ 318) tive history differences to depressive symptom levels
and odds of being highly symptomatic in the two
Age, yr
18–24 25.9 (2.6)** 14.3 (1.3)
cohorts.
25–34 17.0 (1.6) 15.0 (0.9)
35+ 14.5 (2.2) 13.9 (1.3)
Ethnicity (%) RESULTS
Caucasian 13.2 (1.5)*** 11.8 (10.1)***
African-American 24.8 (2.9) 13.5 (10.4) OVERALL COMPARISON OF COHORTS
Hispanic 23.5 (2.3) 18.3 (11.4)
The observed CES-D mean for miscarrying women
Other 19.0 (4.7) 11.7 (10.2)
Language of interview
first interviewed at 6–8 weeks after loss was 18.8, and
Spanish 22.9 (2.2)* 18.0 (10.6)*** substantially higher than that for community women
English 17.0 (1.4) 13.4 (11.0) (14.6) (Table 3). The adjusted dif ference in CES-D
Education means between the two cohorts was 4.9 (95%
oHigh school 24.9 (2.4)*** 20.7 (1.6)*** confidence interval [CI] 2.3–7.4; Table 3).
High school graduate 19.5 (2.5) 18.1 (1.4) Similar results held for comparisons involving highly
Some college 21.4 (2.4) 11.7 (0.9) symptomatic women in the two cohorts. Among
College graduate 11.8 (1.9) 11.0 (1.1) miscarrying women first interviewed at 6–8 weeks after
Marital status loss, 20.2% were highly symptomatic as compared with
Currently single 26.1 (2.4)*** 14.6 (0.9)***
10.1% in the community cohort. The observed odds
Married 14.9 (1.3) 12.4 (1.0)
Other 24.7 (4.5) 18.6 (1.5)
ratio was 2.3 (95% CI 1.3–4.1); the adjusted odds ratio
Living children, n (%) was 2.8 (95% CI 1.4-5.6; Table 3).
0 18.1 (1.7) 13.6 (0.8)**
1 19.7 (2.1) 14.6 (1.8) NUMBER OF CHILDREN
2 17.5 (3.9) 14.4 (1.3)
3+ 19.0 (3.9) 20.2 (1.9) The level of depressive symptoms did not vary with
Prior reproductive losses, n (%) number of children among miscarrying women. By
0 18.0 (1.4) 14.3 (0.7) contrast, depressive symptoms were positively and
1 18.4 (2.9) 18.6 (2.1) significantly associated with number of children among
2+ 24.7 (4.6) 13.6 (3.5) community women (Table 2). However, this difference
w
Note. Values are expressed as mean (SE), unless otherwise noted. in the nature of the two associations, one, absent, the
These tests were performed with age, years of education, number of other, direct, was not statistically significant in adjusted
living children, and number of prior reproductive losses represented analyses based on CES-D scores treated as a contin-
as continuous variables, not in the truncated categorical form uous variable. Logistic regression analysis based on the
displayed in the above table. P values derive from analysis of variance odds of women being highly symptomatic produced
(ANOVA) tests for within-cohort differences in means. P values similar null results.
pertain to two-tailed ANOVA tests for linearity, using 1 df.
CES-D, Center for Epidemiologic Studies-Depression.
*Po.05; ** Po.01; ***P o.001. NUMBER OF PRIOR REPRODUCTIVE
LOSSES
Within the miscarriage cohort, depressive symptoms
increased with the number of prior reproductive
losses (Table 2). Within the community cohort,
depressive symptoms did not vary with prior loss. This
SAMPLE CHARACTERISTICS
difference between the two cohorts in the nature of the
Women in the miscarriage and community cohorts association of depressive symptoms with prior loss, one
were distributed similarly on age, ethnicity, language of direct, the other, absent, was significant at Po.09,
interview, and educational level (Table 1). Mean age of suggesting that miscarriage exerts a disproportionately
the two cohorts combined was approximately 30 years. greater ef fect on women with previous reproductive
About 40% classified themselves as White, 30% as loss. The same pattern of findings held when the effect
Hispanic. Roughly one-quarter had less than a high of miscarriage as a function of prior loss was examined
school education, whereas about 30% were college separately among women in the two cohorts with and
graduates. without children. However, these results for prior
158
TABLE 3. Comparison of CES-D of highly symptomatic women (CES-D 30+) between miscarrying women (first
interviewed at 6–8 weeks after loss) and community womenw
Parameter estimate
Observed CES-D mean (7SE)
Adjusted difference between the two study cohorts, mean (95% CI)a
Observed scoring 30+, % (7SE)
Adjusted odds ratio (95% CI)
w
Note. Ratio of the odds of a woman with Center for Epidemiologic Studies-Depression (CES-D) score 30+ belonging to the miscarriage cohort
to the odds of a woman with CES-D score
a
Means are adjusted by ordinary least squares multiple regression analysis; proportions by maximum likelihood logistic regression analysis. See
text for discussion of covariates.
reproductive loss did not extend to analyses based on
highly symptomatic women.
MATERNAL AGE
We hypothesized that the impact of miscarriage
would be greater for older as compared with younger
women. Among miscarrying women, depressive symp-
toms were significantly inversely related to age
(Table 2). By contrast, depressive symptoms were not
associated with age in the community cohort. Hence,
the ef fect of miscarriage varied as a function of
maternal age, exhibiting a greater depressive impact
on younger as compared with older women (Po.04).
Evidence for a greater ef fect of miscarriage on younger
as compared with older women also held in analyses
based on highly symptomatic women (Po.03).
To elaborate this finding further, we conducted post-
hoc analyses comparing the miscarriage and commu-
nity cohorts on mean CES-D scores and proportion of
women highly symptomatic among women ages 18–24
and 25þ analyzed separately. Among women ages 18–
24, the adjusted dif ference in means between the two
cohorts was 11.5 (95% CI 5.3–17.7), the adjusted odds
ratio was 18.1 (95% CI 2.8–115.3). Among women
ages 25þ the adjusted difference in means between the
two cohorts was 3.0 (95% CI 0.2–5.8); the adjusted
odds ratio was 1.8 (95% CI 0.8–4.1).
Ethnicity, socioeconomic status and marital
status. In both cohorts, CES-D means differed
significantly among ethnic groups. Hispanics, for
example, reported substantially higher depressive
symptom levels on average than did Whites (Table 2).
Also, in both cohorts, CES-D means varied inversely
with socioeconomic status (indexed here by educational
level to increase interpretability), and married women
had the lowest CES-D mean as compared with the
other two marital groups. Hence, the impact of
miscarriage does not appear to vary as a function of
ethnicity, socioeconomic, or marital status, an infer-
ence formally confirmed in adjusted analyses testing
the statistical significance of the corresponding inter-
action term.
Neugebauer
Cohort
Miscarriage Community
(n ¼ 114) (n ¼ 318)
18.8 (1.2) 14.6 (0.6)
4.9 (2.3–7.4)
20.2 (3.8) 10.1 (1.7)
2.8 (1.4–5.6)
DISCUSSION
Among miscarrying women first interviewed at 6–8
weeks after loss, depressive symptom levels were
significantly elevated over those in a comparable
community sample unexposed to recent reproductive
loss. Furthermore, the adjusted odds of a miscarrying
woman being highly symptomatic on the CES-D was
2.8-fold that of a woman without recent loss. The
corresponding odds ratio at 2 weeks after loss was 6.2
(95% CI 3.0–5.8) [Neugebauer et al., 1992b], suggest-
ing that depressive reactions to miscarriage wane over
time but are substantial nonetheless towards the end of
the second month.
That depressive symptoms persist beyond the early
weeks after loss concurs with results from other studies
of miscarriage that also used comparison cohorts.
Beutel et al. [1995] report depressive symptom eleva-
tions among miscarrying women as late as 6 and 12
months after loss as compared with levels in a
community cohort. Janssen et al. [1996] found raised
depressive symptom levels among miscarrying women
at 2.5 months and 6 months after loss, as compared
with a comparison cohort comprising postpartum
women followed over the same period of time. Finally,
a study employing a pregnant comparison cohort
provides partial support for continued elevation of
depressive symptoms into the second month after
miscarriage [Thaper and Thapar, 1992]. Clinicians
should be aware, therefore, that miscarrying women
seen 6–8 weeks after loss, at the time of their first
postmiscarriage gynecologic visit, may well present
with levels of distress and depressive symptoms well
above that of patients attending for a routine visit.
Correct identification of factors that modify the
psychological impact of miscarriage is less straightfor-
ward and can appear at times as counterintuitive.
Among miscarrying women, symptom levels did not
vary with number of children, a result that agrees with
that of three other studies examining single bereaved
cohorts [Friedman and Gath, 1989; Garel et al., 1992;
Lee et al., 1997]. However, these findings neither
support nor contradict our cross-cohort finding that
 Research Article: Depression and Reproductive Loss
having children does not buf fer women from the
depressive effects of miscarriage. For example, if
these other studies had employed a nonbereaved
cohort in which depressive symptoms were exceedingly
low among nonparous women relative to parous
women, we would conclude correctly that being
childless exacerbated the impact of miscarriage.
Other studies of single bereaved cohorts document
an inverse association between depressive symptoms
and number of children [Stirtzinger et al., 1999]; yet
others, a direct association [La Roche et al., 1984].
Again, while these reports contradict our within-cohort
findings, they do not necessarily contradict our cross-
cohort results. None of the studies using a comparison
cohort explored whether having children moderated
the impact of miscarriage, except for our earlier work
(described herein).
Among miscarrying women, depressive symptoms
were higher among those with prior loss and among
younger women. By contrast, in the community cohort,
depressive symptoms did not vary with history of prior
loss or maternal age, thereby indicating that miscar-
riage has a greater impact on women with prior loss
and on younger women.
Some previous single cohort studies report a positive
association between depressive symptoms and maternal
age or between depressive symptoms and prior loss
[Friedman and Gath, 1989; Kennell et al., 1970;
Stirtzinger et al., 1999], and others report no associa-
tion [Benfield et al., 1978; Beutel et al., 1995; Jannsen
et al., 1996; LaRoche et al., 1984; Lee et al., 1997;
Nicol et al., 1986; Tudehope et al., 1986]. Again, in the
absence of comparison cohorts, the relationship
between these study findings and our own, as regards
dif ferential effects of miscarriage as a function of prior
loss and maternal age, is unknownable. Among the
previous studies utilizing a comparison group, Janssen
et al. [1996] found no moderating effect for prior loss,
Beutel et al. [1995] found none for maternal age.
As we have demonstrated, factors modifying the
effect of miscarriage can be discerned only through the
use of unexposed comparison cohorts. Hence, despite
the abundance of studies on depression among
miscarrying women, only the handful using compar-
ison cohorts are able to identify subgroups of
miscarrying women experiencing the greatest increase
in depressive symptoms following loss. Furthermore,
among these studies, few have fully exploited the
opportunity to address the question of ef fect modifica-
tion. Hence, we know the least about which miscarry-
ing women undergo the greatest symptom increase
associated with their loss.
Our current analyses support only one of our three a
priori hypotheses concerning moderating variables;
that is, miscarrying women with prior loss are affected
disproportionately by a new loss. Evidence of a
protective ef fect of already having children was absent
and miscarriage had a disproportionately greater effect
on younger not older women.
159
The tests of these a priori hypotheses among
miscarrying women first interviewed at 2 weeks after
loss produced findings at odds with those reported here.
Having children exerted a powerful protective effect,
e.g., among women with three or more children, mean
CES-D scores for miscarrying women and community
women did not differ. By contrast, in the sample
interviewed at 2 weeks after loss, neither prior loss nor
maternal age moderated the impact of miscarriage.
No ready explanation for these contrasting results is
available. A change over time in the factors that modify
the impact of miscarriage is one possible but not
entirely satisfactory explanation for these differences.
When the miscarrying women first interviewed at 2
weeks after loss were reinterviewed at 6–8 weeks, the 2-
week patterns regarding living children, prior losses,
and maternal age were sustained, although symptom
levels overall were considerably lower. The origin of
these discrepancies and their possible implications for
the timing of assessments after loss and broadening of
the list of candidate confounders awaits elucidation.
Neither marital status, ethnicity, nor socioeconomic
status moderated the effect of miscarriage on depres-
sive symptoms, a finding that obtained both in
miscarrying women first interviewed at 2 weeks and
at 6–8 weeks after loss. Similarly, null results for
marital and socioeconomic status were reported by
Beutel et al. [1995].
The present study suffers from limitations typical of
hospital based observational as contrasted with experi-
mental study designs. The depressive symptom levels
of the miscarrying women may not be representative of
miscarrying women generally. While among identified
miscarrying women attending the medical center,
interviewed and uninterviewed did not differ on major
sociodemographic variables, they might nonetheless
differ on depressive symptom levels. The same caveats
apply to women consenting to be interviewed in the
community cohort. The fact that women interviewed at
6–8 weeks after miscarriage comprise women who
could not be reached at 2 weeks also raises a question as
to their representativeness. The inconsistency in the
patterns found for moderator variables between mis-
carrying women assessed at 2 weeks and at 6–8 weeks
might be explicable on these grounds.
CONCLUSION
Hopefully, the current substantive findings, together
with those reported in earlier studies, will raise
awareness among gynecologists of the possible persis-
tence of elevated depressive symptom levels among
miscarrying women even at 6–8 weeks after loss.
Increased awareness should lead to greater likelihood
of recognition of depressive symptoms and earlier
scheduling of a follow-up visit or telephone call or
appropriate mental health referral.
Advances in our understanding of the duration of
depressive reactions to reproductive loss will require
160 Neugebauer
assessments of outcome at more precise time intervals,
standardized measures of outcome, samples of suffi-
cient size to permit adequate control of potentially
confounding factors, and equally important, to exclude
limited statistical power as the more likely explanation
for absent associations. Progress will also depend upon
the use of comparison cohorts that alone afford the
opportunity to assess the magnitude of the ef fect of
miscarriage on depressive symptoms and disorder and
to identify factors that enhance or ameliorate the toll
taken by loss.
Acknowledgments. I gratefully acknowledge the
generous assistance and guidance of Drs. J. Kline, Z.
Stein, M. Susser, and D. Warburton who collaborated
in the study from which these data were drawn. Thanks
also to other collaborators, Drs. P. Shrout, P. O’Con-
nor, A. Skodol, J. Wicks, and the late J. Johnson, for
their help in the conduct and analysis of the original
study.
REFERENCES
Aneshensel CS, Frerichs RR, Clark VA, Yokopenic PA. 1982.
Measuring Depression in the community: a comparison of
telephone and personal interviews. Public Opinion Q 46:110–121.
Benfield DG, Leib SA, Vollman JH. 1978. Grief response of parents
to neonatal death and parent participation in deciding care.
Pediatrics 62:171–177.
Beutel M, Deckardt R, Von Rad M, Weiner H. 1995. Grief and
depression after miscarriage: Their separation, antecedents and
course. Psychosomatic Med 57:517–526.
Boyd JH, Weissman MM, Thompson D, Myers JK. 1982. Screening
for depression in a community sample. Arch Gen Psychiatry
39:1195–1200.
Clarke M, Williams AJ. 1979. Depression in women after perinatal
death. Lancet 2:916–917.
Cordle CJ, Prettyman RJ. 1994. A 2-year follow-up of women
who have experienced early miscarriage. J Reprod Infant Psychol
12:37–43.
Forrest GC, Standish E, Baum JD. 1982. Support after perinatal
death: A study of support and counseling after perinatal bereave-
ment. BMJ 285:1475–1479.
Friedman T, Gath D. 1989. The psychiatric consequences of
spontaneous abortion. Br J Psychiatry 155:810–813.
Garel M, Blondel B, Lelong N, Papin C, Bonenfant S, Kaminski M.
1992. Reactions Depressives après une fausse-couche. Contracept
Fertil Sex 20:75–81.
Geller P, Klier C, Neugebauer R. 2001. Anxiety disorders following
miscarriage. J Clin Psychiatry 62:432–438.
Graham MA, Thompson SC, Estrada M, Yonekura ML. 1987.
Factors affecting psychological adjustment to a fetal death. Am J
Obstet Gynecol 157:254–257.
Hochstim JR. 1967. A critical comparison of three strategies
for collecting data from households. Am Stat Assoc J September
62:976–989.
Kennell JH, Slyter H, Klaus MH. 1970. The mourning response of
parents to the death of a newborn infant. N Engl J Med 283:
344–349.
Klier CM, Geller PA, Neugebauer R. 2000. Minor depressive
disorder in the context of miscarriage. J Affect Dis 59:13–21.
Kline J, Stein Z, Susser M. 1989. Conception to birth: Epidemiology
of prenatal development. New York: Oxford University Press.
p 43–68.
Kline J, Hutzler M, Levin B, Stein Z, Susser M, Warburton D. 1991a.
Marijuana and spontaneous abortion of known karyoptype. Pediatr
Perinat Epidemiol 5:320–332.
Kline J, Levin B, Silverman J, Kinney A, Stein Z, Susser M,
Warburton D. 1991b. Caffeine and spontaneous abortion of
known karyotype. Epidemiology 2:409–417.
La Roche C, Lalinec-Michaud M, Engelsmann F, Fuller N, Copp M,
McQuade-Soldatos L, Azima R. 1984. Grief reactions to perinatal
death: A follow-up study. Can J Psychiatry 29:14–19.
Lee DTS, Wong CK, Cheung LP, Leung HCM, Haines CJ, Chung
TKH. 1997. Psychiatric morbidity following miscarriage: a
prevalence study of Chinese women in Hong Kong. J Affect Dis
43:63–68.
Leimbach R. 1982. Alternatives to the face-to-face interview for
collecting gerontological needs assessment data. Gerontologist
22:78–82.
Myers JM, Weissman MM. 1980. Use of a self-report scale to detect
depression in a community sample. Am J Psychiatry 137:1080–1084.
National Center for Health Statistics. Vital Statistics of the United
States. 1992. Volume 1, Natality. Washington, DC: U.S. Public
Health Service; 1995. Publication PHS 96–1100.
Neugebauer R, Kline J, O’Connor P, Shrout P, Johnson J, Skodol A,
Wicks J, Susser M. 1992a. Depressive symptoms in women in the
six months following miscarriage. Am J Obstet Gynecol 166:
104–109.
Neugebauer R, Kline J, O’Connor P, Shrout P, Johnson J, Skodol A,
Wicks J, Susser M. 1992b. Determinants of depressive symptoms
in the early weeks after miscarriage. Am J Public Health 82:
1332–1339.
Neugebauer R, Kline J, Shrout P, Skodol A, O’Connor P, Geller PA,
Stein Z, Susser M. 1997. Major depressive disorder in the 6 months
after miscarriage. JAMA 277:383–388.
Nicol MT, Tompkins JR, Campbell NA, Syme GJ. 1986. Maternal
grieving response after perinatal death. Med J Aust 144:
287–289.
Nikcevic AV, Tunkel SA, Kuczmierczyk AR, Nicolaides KH. 1999.
Investigation of the cause of miscarriage and its influence on
women’s psychological distress. Brit J Obst Gyn 106:808–813.
Peppers LG, Knapp RJ. 1980. Maternal Reactions to involuntary
fetal/infant death. Psychiatry 43:155–159.
Radloff LS. 1977. The CES-D scale: A self-report depression
scale for research in the general population. Appl Psychol Meas
1:385–401.
Robins LN, Regier DA, editors. 1991. Psychiatric disorders in
America: The epidemiological catchment area study. New York:
Free Press.
Robinson G, Stirtzinger R, Steward DE. 1994. Psychological
reactions in women followed for one year after miscarriage. J
Reprod Infant Psychol 12:31–36.
Rowe J, Clyman R, Green C, Mikkelsen C, Haight J, Ataide L. 1978.
Follow-up of families who experience a perinatal death. Pediatrics
62:166–170.
Seibel M, Graves WL. 1980. The psychological implications of
spontaneous abortions. J. Reprod Med 25:161–165.
Slade P. 1994. Predicting the psychological impact of miscarriage. J
Reprod Infant Psychology 12:5–16.
Stirtzinger RM, Robinson GE, Steward DE, Ralevsky E. 1999.
Parameters of grieving in spontaneous abortion. Int J Psychiatry
Med 29:235–249.
Swanson KM. 2000. Predicting depressive symptoms after miscar-
riage: A path analysis based on the Lazarus paradigm. J Women’s
Health Gender-Based Med 9:191–206.
 Research Article: Depression and Reproductive Loss 161

Thaper AK, Thaper A.1992. Psychological sequelae of miscarriage: A
controlled study using the general health questionnaire and the
hospital anxiety and depression scaled. Br J Gen Pract 42:94–96.
Toedter LJ, Lasker JN, Alhadeff JM.1988. The Perinatal Grief Scale:
development and initial validation. Am J Orthopsychiatry 58:
435–449.
Tudehope DI, Iredall J, Rodgers D, Gunn A. 1986. Neonatal death:
Grieving families. Med J Aust 144:290–292.
Weissman MM, Sholomskas D, Pottenger M, Prosoff BA,
Locke BZ. 1977. Assessing Depressive symptoms in five
psychiatric populations: A validation study. Am J Epidemiol
106:203–213.
Zuckerman B, Amaro H, Bauchner H, Cabral H.1989. Depressive
symptoms during pregnancy: Relationship to poor health beha-
viors. Am J Obstet Gynecol160:1107–1111.