DOI: 10.1111/1471-0528.

14027 General obstetrics

www.bjog.org

Women’s prepregnancy underweight as a risk

factor for preterm birth: a retrospective study
AI Girsen,a JA Mayo,b SL Carmichael,b CS Phibbs,b,c BZ Shachar,b DK Stevenson,b DJ Lyell,a
GM Shaw,b JB Gouldb On behalf of the March of Dimes Prematurity Research Center at Stanford
University School of Medicine
a
Department of Obstetrics & Gynecology, Stanford University School of Medicine, Stanford, CA, USA b Department of Pediatrics, Division of
Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, CA, USA c Health Economics Resource Center,
Veterans Affairs Palo Alto Healthcare System, Menlo Park, CA, USA
Correspondence: AI Girsen, MD, Department of Obstetrics & Gynecology, HH333 MC 5317, 300 Pasteur Dr., Stanford, CA 94305, USA.
Email anna.girsen@gmail.com

Accepted 13 February 2016. Published Online 13 May 2016.

Objective To investigate the distribution of known factors for
preterm birth (PTB) by severity of maternal underweight; to
investigate the risk-adjusted relation between severity of
underweight and PTB, and to assess whether the relation differed
by gestational age.
Design Retrospective cohort study.
Setting State of California, USA.
Methods Maternally linked hospital and birth certificate records of
950 356 California deliveries in 2007–2010 were analysed. Singleton
live births of women whose prepregnancy body mass index (BMI)
was underweight (<18.5 kg/m2) or normal (18.50–24.99 kg/m2)
were analysed. Underweight BMI was further categorised as: severe
(<16.00), moderate (16.00–16.99) or mild (17.00–18.49). PTB was
grouped as 22–27, 28–31, 32–36 or <37 weeks (compared with 37–
41 weeks). Adjusted multivariable Poisson regression modeling was
used to estimate relative risk for PTB.
Main outcome measures Risk of PTB.
Results About 72 686 (7.6%) women were underweight.
Increasing severity of underweight was associated with increasing
percent PTB: 7.8% (n = 4421) in mild, 9.0% (n = 1001) in
moderate and 10.2% (475) in severe underweight. The adjusted
relative risk of PTB also significantly increased: adjusted relative
risk (aRR) = 1.22 (95% CI 1.19–1.26) in mild, aRR = 1.41 (95%
CI 1.32–1.50) in moderate and aRR = 1.61 (95% CI 1.47–1.76) in
severe underweight. These findings were similar in spontaneous
PTB, medically indicated PTB, and the gestational age groupings.
Conclusion Increasing severity of maternal prepregnancy
underweight BMI was associated with increasing risk-adjusted
PTB at <37 weeks. This increasing risk was of similar magnitude
in spontaneous and medically indicated births and in preterm
delivery at 28–31 and at 32–36 weeks of gestation.
Keywords Pregnancy, preterm birth, underweight.
Tweetable abstract Increasing severity of maternal underweight
BMI was associated with increasing risk of preterm birth.
Linked article This article is commented on by A Cristina Rossi,
p. 2008 in this issue. To view this mini commentary visit http://
dx.doi.org/10.1111/1471-0528.14129.

Please cite this paper as: Girsen AI, Mayo JA, Carmichael SL, Phibbs CS, Shachar BZ, Stevenson DK, Lyell DJ, Shaw GM, Gould JB On behalf of the March
of Dimes Prematurity Research Center at Stanford University School of Medicine. Women’s prepregnancy underweight as a risk factor for preterm birth: a
retrospective study. BJOG 2016;123:2001–2007.

associate with PTB.4,5 Recent studies have demonstrated

Introduction
With approximately 13 million babies born each year
before 37 weeks of gestation,1 preterm birth (PTB) is a
leading cause of infant mortality and neonatal morbidity.2
Although multiple risk factors have been related to PTB, it
continues to be a complex phenomenon without a cure.
One of the potentially modifiable risk factors for PTB is
maternal body mass index (BMI).3–5 Both low (<18.5) and
high (>29) body mass index (BMI) have been shown to
that the relation between obesity and prematurity is influ-
enced by the extent of obesity, type of PTB, presence or
absence of comorbidities, parity, and gestational age.4,6,7 In
addition to the worldwide concern about the negative
health effects of increasing obesity, maternal underweight
and malnutrition are serious problems8,9 that may have
both short- and long-term consequences.10,11 However, so
far, only a few studies have investigated effects of under-
weight severity (severe, BMI <16; moderate, BMI 16–16.9;

ª 2016 Royal College of Obstetricians and Gynaecologists 2001

 Girsen et al.
mild, BMI 17–18.49 kg/m2) on broad categories of gesta-
tional age reflecting PTB12 and no large studies have
addressed which factors are important to the relation
between underweight and PTB.
In this large population-based cohort study, we had four
specific aims: (1) to assess the distribution of known risk
factors for PTB by severity of maternal underweight; (2) to
assess whether the relation between severity of underweight
and PTB persisted after adjusting for these risk factors; (3)
to assess whether the adjusted relation between under-
weight severity and PTB differed by gestational age; and (4)
to examine the hypothesis that risk factors for PTB would
have a larger effect size in underweight women than in
normal weight women.
Methods
Data for this study come from 2007 to 2010 California birth
cohorts reflecting California vital statistics birth records
linked with the Office of Statewide Health and Planning
(OSHPD) maternal and infant hospital discharge data. These
data contain information on a range of maternal and preg-
nancy characteristics found on the birth certificate paired
with clinical details from the delivery hospitalisation for
nearly all inpatient live births, and has been well described
elsewhere.13 Stanford University Institutional Review Board
and the California State Committee for the Protection of
Human Subjects reviewed and approved this study.
Demographic risk factors for PTB derived from birth
certificates included maternal race/ethnicity, age, height,
prepregnancy weight, education, parity, receipt of prenatal
care, payer for the delivery, and gestational age at delivery
based on obstetric estimate reported on the birth certifi-
cate.14 In addition to maternal demographics we also
included other potential behavioural risk factors for pre-
term birth. Maternal eating disorder was defined based on
the International Classification of Diseases, 9th revision, Clin-
ical Modification (ICD-9-CM) codes (307.1, 307.50, 307.51)
in hospital discharge data, as were maternal alcohol (303,
305.0) and drug (304, 305.2–.9, 648.3) use during preg-
nancy. Smoking was defined as either birth certificate infor-
mation of ≥1 cigarettes per day during pregnancy or based
on smoking-related ICD-9 codes (305.1, 649.0) in the
delivery hospital discharge data.
Maternal comorbidities that have been associated with
preterm birth were identified from ICD9-CM codes reported
on the birth hospitalisation data set. Specifically, comorbidi-
ties included in analysis were: pre-existing diabetes (ICD-9
CM 250, 648.0); gestational diabetes (648.8); pre-existing
hypertension (401-405, 642.0, 642.1, 642.2, 642.7, 642.9);
gestational hypertension/pre-eclampsia/eclampsia (642.3,
642.4, 642.5, 642.6, 642.7); placenta praevia (641.0, 641.1);
placental abruption (641.2) and anaemia (280–285, 648.2).
2002
PTB was defined as a live birth occurring at less than
37 weeks of gestation but was also assessed in gestational
categories of 22–27 weeks, 28–31 weeks, and 32–36 weeks,
each compared with term births at 37–41 weeks. PTB was
further subtyped based on maternal ICD-9-CM diagnosis
and procedure codes along with birth certificate codes in a
hierarchical classification.4 First, spontaneous PTBs were
identified as those births <37 weeks with preterm prema-
ture rupture of membranes, premature labour or tocolytics.
Medically indicated PTBs were those induced or delivered
by caesarean section <37 weeks and not previously identi-
fied as spontaneous. All births <37 weeks not captured by
the above groups were considered unclassifiable.
BMI was calculated based on recorded height and
prepregnancy weight (BMI = weight (in kg)/height2(in
m)). Underweight BMI was defined as <18.5 kg/m2 and
further categorised into severe (<16 kg/m2), moderate
(16–16.9 kg/m2) and mild (17–18.49 kg/m2). Normal BMI
was defined as 18.5–24.9 kg/m2.15 Data on maternal
prepregnancy weight and height were self-reported.
During 2007–2010, there were 2 027 983 singleton live
birth vital statistic records linked with maternal and infant
hospital discharge summaries. Of these, we identified births
with the following primary exclusion criteria (not mutually
exclusive): gestational age <22 or >41 weeks (n = 30 617),
missing maternal height (n = 105 635), missing prepreg-
nancy weight (n = 158 395), and overweight or obese preg-
nancy BMI (n = 844 893). This left a total of 985 773
births to underweight and normal BMI mothers of which
we further excluded (not mutually exclusive) missing edu-
cation (n = 32 953), maternal age <13 or >55 years
(n = 26), missing parity or >10 (n = 423) or missing race/
ethnicity (n = 16 297). Our final analytic cohort consisted
of 950 356 singleton live births born between 22 and
41 weeks of gestation to normal or underweight women
with complete covariate information. Because the purpose
of the study was to assess the impact of underweight on
PTB, the cohort was limited to deliveries at 22–41 weeks of
gestation.
Statistical analysis
Statistical analysis was performed using SAS version 9.3
(SAS Institute, Cary, NC, USA). First we compared mater-
nal and delivery variables (Table 1), maternal behavioural
factors (Table 2) and medical conditions (Table 2) between
underweight categories and women with normal prepreg-
nancy BMI. Bivariate comparisons of continuous variables
were performed using analysis of variance (ANOVA), and
comparison of categorical variables using Chi-squared test.
The level of significance was set at P < 0.05.
The association between underweight BMI categories and
PTB was measured with adjusted relative risks (aRR) and
95% confidence intervals (CI) derived from multivariable
ª 2016 Royal College of Obstetricians and Gynaecologists
 Prepregnancy underweight and risk of preterm birth

Table 1. Characteristics of the study subjects with underweight prepregnancy BMI (severe, moderate, mild) and normal prepregnancy BMI

Variable Underweight BMI categories (kg/m2) P-value*

Severe (<16) Moderate (16–16.9) Mild (17–18.49) Normal (18.5–24.9)

n = 4665 n = 11108 n = 56913 n = 877670

Maternal age in years (SD) 25.2 (6.1) 25.8 (6.2) 26.9 (6.5) 28.1 (6.4) <0.001
Maternal height in inches (SD) 66.0 (4.1) 64.7 (3.1) 64.2 (2.8) 63.7 (2.7) <0.001
Maternal race/ethnicity
Non-Hispanic White 21% (968) 26% (2882) 30% (16 919) 32% (279 545) <0.001
Non-Hispanic Black 6% (265) 6% (706) 5% (3050) 5% (41 730)
Asian 24% (1100) 24% (2693) 26% (14 543) 14% (118 945)
Hispanic 45% (2118) 38% (4268) 35% (19 908) 45% (39 8216)
Other 5% (214) 5% (559) 4% (2493) 4% (39 234)
Maternal education
Some high school or less 31% (1459) 25% (2725) 21% (11 956) 22% (195074) <0.001
High school graduate 29% (1375) 29% (3224) 25% (14387) 24% (210910)
Some college 20% (946) 22% (2484) 22% (12347) 22% (191438)
College graduate or more 19% (885) 24% (2675) 32% (18223) 32% (280248)
Parity
1 58% (2691) 56% (6237) 55% (31 169) 46% (402 570) <0.001
≥2 42% (1974) 44% (4871) 45% (25 744) 54% (475 100)
Prenatal care initiation
In first 5 months 91% (4265) 92% (10 194) 93% (53 100) 94% (825 314) <0.001
6 months or later/no initiation/unknown 9% (400) 8% (914) 7% (3813) 6% (52 356)
Payer for prenatal care
MediCal (Public) 59% (2738) 50% (5598) 44% (24 790) 42% (367 834) <0.001
Private 34% (1590) 43% (4789) 51% (28 754) 53% (464 187)
NA/Uninsured/Unknown 4% (192) 3% (367) 3% (1672) 2% (19 493)
Other 3% (145) 3% (354) 3% (1697) 3% (26 156)
Prior preterm delivery at <37 weeks
No 99% (4637) 99% (11 034) 99% (56 602) 99% (872 956) 0.285
Yes 1% (28) 1% (74) 1% (311) 1% (4714)
Preterm delivery (<37 weeks)
Spontaneous 8% (350) 7% (734) 6% (3264) 5% (42 670) <0.001
Medically indicated 2% (84) 2% (176) 1% (724) 1% (10 283)
Unclassified 1% (41) 1% (91) 1% (433) 1% (5191)

Data are presented as mean (SD) for maternal age and height, and % (n) for all the other variables.
*ANOVA or chi-square test used for comparison.
BMI, body mass index.

Poisson regression models. Potential confounders were
selected based on their significance in the univariable analy-
sis (P < 0.1) and because they have been associated with
increased risk for PTB. The potential confounders included
in the multivariable model were maternal age (continuous),
prenatal care initiation (during first 5 months, 6 months
or later/no initiation/unknown), maternal education (some
high school or less, high school graduate, some college, col-
lege graduate or more), race/ethnicity (Non-Hispanic
White, Non-Hispanic Black, Asian, Hispanic, Other), parity
(nulliparous, multiparous), smoking during pregnancy (yes,
no), presence of eating disorder (yes/no), anaemia (yes/no),
pre-existing diabetes (yes/no), pre-existing hypertension
(yes/no), gestational diabetes (yes/no), gestational
hypertension (yes/no), placental abruption (yes/no), and
maternal height (continuous) to reduce further potential
residual confounding associated with the BMI algorithm.16
Because risk-adjusted PTB could result from medical inter-
vention, we compared the relation between severity of
underweight and PTB in births that were spontaneous and
in births that resulted from medical intervention.
Results
Among a total of 950 356 women included in analyses,
72 686 (7.6%) had an underweight prepregnancy BMI;
0.5% had severe, 1.2% moderate, and 6.0% mild under-
weight. An increasing trend of all PTBs (<37 weeks) was

ª 2016 Royal College of Obstetricians and Gynaecologists 2003

 Girsen et al.

Table 2. Maternal behavioural factors and medical conditions in women with underweight prepregnancy BMI and normal BMI

Underweight BMI categories (kg/m2) P-value*

Severe Moderate (16–16.9) Mild (17–18.49) Normal (18.5–24.9)

n = 4665 n = 11 108 n = 56913 n = 877 670

Maternal behaviours
Smoking during pregnancy 5.40% (252) 5.30% (589) 4.12% (2346) 2.77% (24 297) <0.001
Alcohol use during pregnancy 0.11% (5) 0.09% (10) 0.11% (65) 0.10% (906) 0.84
Drug abuse during pregnancy 1.78% (83) 1.68% (187) 1.31% (745) 0.99% (8717) <0.001
Eating disorder 0.06% (3) 0.06% (7) 0.02% (11) 0.01% (69) <0.001
Maternal medical conditions
Anaemia 9.65% (450) 9.48% (1053) 8.50% (4839) 7.93% (69 641) <0.001
Pre-existing diabetes 0.09% (4) 0.18% (20) 0.15% (87) 0.34% (2997) <0.001
Gestational diabetes 3.52% (164) 3.38% (375) 3.17% (1804) 4.40% 38 593 <0.001
Pre-existing hypertension 0.43% (20) 0.45% (50) 0.41% (236) 0.76% (6714) <0.001
Gestational hypertension/pre-eclampsia/eclampsia 3.99% (186) 3.15% (350) 2.94% (1674) 3.78% (33 215) <0.001
Placental abruption 1.22% (57) 0.98% (109) 1.06% (601) 0.86% (7573) <0.001
Placenta praevia 0.73% (34) 0.64% (71) 0.73% (415) 0.68% (5981) 0.52

Data are presented as % (n).

*Chi-square test used for comparison.

noted by increasing severity of maternal underweight: 7.8%
in mild (n = 4421 PTBs), 9.0% in moderate (n = 1001)
and 10.2% in severe underweight (n = 475). The unad-
justed relative risks were RR = 1.17 (95% CI 1.14–1.21) in
mild, RR = 1.36 (95% CI 1.28–1.45) in moderate and
RR = 1.54 (95% CI 1.40–1.68) in the severe underweight
group.
Maternal demographics, medical conditions and beha-
vioural risk factors for PTB and their relation to severity of
underweight are presented in Tables 1 and 2. Compared
with women with a normal BMI, women with severe
underweight were slightly younger, less likely to be non-
Hispanic White, less educated, more often nulliparous and
had received public (MediCal) insurance more often. The
percentage of late prenatal care initiation was highest with
severe underweight as were the percentages of spontaneous
and medically indicated PTB deliveries. However, the rate
of prior PTBs was similar across all underweight categories
(Table 1).
Women with mild, moderate, and severe underweight
demonstrated higher frequencies of smoking and drug
abuse during pregnancy compared with normal weight
women, whereas alcohol use during pregnancy was similar
between the groups. Anaemia during pregnancy was
increased among those underweight compared with women
of normal BMI, but underweight women were less likely to
have pre-existing diabetes, gestational diabetes or pre-exist-
ing hypertension compared with women with normal BMI
(Table 2).
Table 3 compares the observed relation between severity
of underweight and % PTB to the risk-adjusted relation for
(1) all preterm births, (2) the 73.4% of preterm deliveries
that were spontaneous, and (3) the 17.6% that were medi-
cally indicated (note: 9.0% could not be classified). The
observed relative risk (RR) for PTB (<37 weeks) increased
from RR = 1.17 (95% CI 1.14–1.21) in mildly underweight
women to RR = 1.54 (95% CI 1.40–1.68) in those who were
severely underweight. Although the aRRs were slightly higher
than the observed RRs (mild: aRR = 1.22; 95% CI 1.19–1.26
and severe: aRR = 1.61; 95% CI 1.47–1.76), there were no
statistically significant differences in the extent of the associ-
ation between severity of underweight and increasing PTB as
estimated by RR and aRR for all deliveries, spontaneous pre-
term deliveries, and medically indicated deliveries. Further-
more, the extent to which increasing severity of underweight
was associated with increasing risk for PTB, was similar for
all preterm deliveries, spontaneous preterm deliveries, and
medically indicated preterm deliveries (Table 3).
Because the relation between obesity and PTB has been
shown to increase with decreasing gestational age groupings
we examined the potential effect of gestational age in
underweight women. The risk-adjusted relation between
severity of underweight and PTB is shown for three gesta-
tional groupings in Table 4. Although estimates at 22–
27 weeks were limited by small sample size, based on the
overlapping confidence intervals, there was no evidence of
an increase in effect size as estimated by aRRs in the mod-
erately preterm (28–31 weeks) and late preterm (32–
36 weeks) groupings (Table 4). Exclusion of cases with a
history of prior PTB, did not significantly change the aRRs
across underweight categories for all PTBs, or the above
groupings (Table S1).

2004 ª 2016 Royal College of Obstetricians and Gynaecologists

 Prepregnancy underweight and risk of preterm birth

Table S2 examines the hypothesis that risk factors for PTB

(1.43, 2.21)
(1.32, 1.78)
(1.15, 1.34)
will have a larger effect size in underweight than in normal

Model adjustments include: maternal age, height, prenatal care initiation, maternal education, race/ethnicity, parity, smoking, drug abuse, presence of eating disorder, anaemia, pre-existing
aRR (CI)
Table 3. Observed unadjusted and risk adjusted associations between all preterm births (All PTB) and preterm birth subtypes (Spontaneous PTB and Medically indicated PTB) and maternal

Medically indicated PTB <37 weeks

weight women. For each risk factor, the aRR risk of the PTB

(1.0)
at <37 weeks among underweight women (all categories)

ref
1.78
1.53
1.24
and among normal weight women are compared. No associ-
ation was noted in normal weight women, but decreased par-
ity was related to decreased risk of PTB among underweight
(1.28, 1.97)
(1.19, 1.60)
(1.02, 1.18)
women (Table S2). Although limited by small numbers, eat-
RR (CI)

ing disorder was associated with an increased risk for PTB

(1.0)

among underweight women and not among normal weight

ref
1.59
1.38
1.10

women. The relative risk of preterm delivery associated with

smoking, drug and alcohol use, anaemia, pre-existing dia-
84
176
724
10 283

betes, pre-existing hypertension, gestational hypertension,

n

placenta praevia and placental abruption were similar in

both underweight and normal weight women (Table S2).
(1.46, 1.81)
(1.31, 1.51)
(1.18, 1.27)
aRR (CI)

Discussion
(1.0)
Spontaneous PTB <37 weeks

Main findings
ref
1.62
1.41
1.22

Our results based on almost a million live births demon-

strate that the risk for PTB increased with the severity of
(1.40, 1.73)
(1.27, 1.47)
(1.14, 1.23)

underweight, and that this relation persisted even after

RR (CI)

adjusting for maternal characteristics, pre-existing maternal

aRR, adjusted relative risk; BMI, body mass index; CI, confidence interval; RR, observed unadjusted relative risk.
(1.0)

comorbidities and behavioural risk factors. We also found

diabetes, pre-existing hypertension, gestational diabetes, gestational hypertension, and placental abruption.
ref
1.56
1.37
1.18

that the strength of the relation was similar in medically

indicated and spontaneous births, and at 28–31 and 32–
350
734

42 670
3264

36 weeks of gestation. Although we hypothesised that risk

n

factors for PTB would have a greater effect in underweight

women, our results did not support this hypothesis.
(1.47, 1.76)
(1.32, 1.50)
(1.19, 1.26)

Strengths and limitations

aRR (CI)

(1.0)

The population-based California data in this study allowed

for PTB stratification by three gestational age groups as
1.61
1.41
1.22
ref
All PTB <37 weeks

well as by clinical subtypes, and increased the generalisabil-

ity of our findings. A limitation is that our data were
(1.40, 1.68)
(1.28, 1.45)
(1.14, 1.21)

derived from birth certificates and discharge databases

RR (CI)

with their inherent errors. Some behavioural factors that

(1.0)

were investigated, i.e. drug abuse and eating disorder, have

1.54
1.36
1.17
ref

been shown to be poorly recorded16,17 and thus could have

been underreported in this study. In addition, we were lim-
ited to investigating BMI derived from self-reported weight
58144
475
1001
4421
underweight categories versus normal BMI

and height information, which has shown previously to

relate to biased risk estimates of PTB.18 Lastly, this large-
Moderate underweight (16–16.99)

scale study cannot identify specific mechanisms underlying

the association between underweight and PTB. However,
Mild underweight (17–18.49)

our study adds to the literature and, importantly, may offer

Severe underweight (<16)

background for more specific, mechanistic studies.

Normal (18.5–24.99)

Interpretation
BMI (kg/m2)

Our results confirm the findings of prior studies among

underweight women5,12 and bring new insights to this
rather understudied topic. Previously, some smaller, single-
centre studies have documented the relation between

ª 2016 Royal College of Obstetricians and Gynaecologists 2005

 Girsen et al.

Table 4. The association between underweight BMI categories and all preterm births (PTB) at 22–27, 28–31 and 32–36 weeks of gestation
compared with normal BMI presented as adjusted relative risks (aRR)

BMI (kg/m2) PTB 22–27 weeks PTB 28–31 weeks PTB 32–36 weeks

n aRR (CI) n aRR (CI) n aRR (CI)

Severe underweight (<16) 16 1.22 (0.74, 1.99) 36 1.62 (1.16, 2.25) 423 1.65 (1.50, 1.82)
Moderate underweight (16–16.99) 40 1.24 (0.90, 1.69) 90 1.64 (1.33, 2.03) 871 1.41 (1.31, 1.50)
Mild underweight (17–18.49) 181 1.18 (1.01, 1.37) 338 1.25 (1.12, 1.40) 3902 1.23 (1.19, 1.27)
Normal (18.5–24.99) 2342 ref (1.0) 4490 ref (1.0) 51 312 ref (1.0)

aRR, adjusted relative risk; BMI, body mass index; CI, confidence interval.
Model adjustments included: maternal age, height, prenatal care initiation, maternal education, race/ethnicity, parity, smoking, drug abuse,
presence of eating disorder, anaemia, pre-existing diabetes, pre-existing hypertension, gestational diabetes, gestational hypertension, and
placental abruption.

underweight and preterm delivery,19,20 but without cate-
gorising underweight by its severity. In addition, Salihu
et al.12 showed that women in all underweight categories
had increased risk of PTB at <37 weeks and at <33 weeks
and that the extent of risk was dependent upon the severity
of underweight. With our substantially larger cohort, we
were able to demonstrate a relation between severity of
underweight and PTB at both 28–31 and 32–36 weeks,
even after multiple adjustments for confounders. In addi-
tion, after excluding women with prior preterm birth, we
found that the relation between underweight categories and
the risk of PTB at 28–31; 32–36 and <37 weeks of gestation
remained essentially unchanged. Furthermore, although at
22–27 weeks of gestation we were likely underpowered to
adequately investigate differences among severe and moder-
ate underweight groups, the risk of PTB was significantly
higher among mild underweight (n = 181) compared with
normal weight women (n = 2342).
Previously, multiple studies have demonstrated the com-
plex relation between maternal obesity and increased risk
of PTB.21 Although both obesity and underweight increase
the risk of PTB with increasing severity,7,12 many of the
factors that play a critical role in the obesity–preterm rela-
tion4,6,7 do not affect the relation between underweight and
PTB. For example, in this study, risk of PTB was similar in
medically indicated and spontaneous deliveries.
Although several factors have been proposed, the mecha-
nisms behind a PTB of underweight women are unknown.
We investigated the effect of maternal pre-existing condi-
tions and behavioural factors on PTB. Not surprisingly,
women in all underweight categories had fewer diabetic
and hypertensive disorders compared with normal weight
women, whereas anaemia occurred more often in under-
weight women. However, the independent relative risks of
PTB associated with smoking, drug and alcohol use, anae-
mia, pre-existing diabetes, pre-existing hypertension, gesta-
tional hypertension, placenta praevia and placental
abruption were similar in underweight and normal weight
women. Thus, although behavioural and medical risk fac-
tors for PTB among underweight women are of concern,
we found insufficient evidence that their effect size was
enhanced in underweight compared with normal weight
women. Although limited by a small number of cases,
maternal eating disorder was associated with PTB among
underweight women and not in normal weight women,
which is in line with the recent study by Linna et al.22 It is
possible that there is a direct association between maternal
underweight and PTB due to the lack of nutrients or there
is an indirect subtle effect of multiple other behavioural
factors such as smoking, poor diet, and medical illness.
Studies with more detailed information on such factors are
needed to investigate the complex relation between under-
weight and PTB.
Conclusion
In conclusion, our study points out that women in all
underweight BMI categories at prepregnancy are at
increased risk of preterm delivery, even after adjustment
for maternal characteristics, comorbidities, and behavioural
factors related to maternal underweight. Based on our Cali-
fornia estimate that 7.6% of pregnant women are under-
weight, our findings support the potential importance of
interventions to reduce prepregnancy underweight as an
important strategy to reduce premature births.
Disclosure of interests
None declared. Completed disclosure of interests form
available to view online as supporting information.
Contribution to authorship
AG, JM, SC, DL, GS, JG designed the research; JM analysed
data; AG, JM, SC, CP, BS, DL, DS, GS, JG drafted and
revised the manuscript.

2006 ª 2016 Royal College of Obstetricians and Gynaecologists


Details of ethical approval
Stanford University Institutional Review Board and the
California State Committee for the Protection of Human
Subjects reviewed and approved this study (Project #24543,
approved on 11/18/2014).
Funding
This work was supported by the March of Dimes Prema-
turity Research Center at Stanford University, the Stan-
ford Child Health Research Institute and the Stanford
Clinical and Translational Science Award (CTSA) to
Spectrum (UL1 TR001085). The CTSA program is led by
the National Center for Advancing Translational Sciences
(NCATS) at the National Institutes of Health (NIH).
The content is solely the responsibility of the authors
and does not necessarily represent the official views of
the NIH.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Table S1. The association between underweight BMI cat-
egories and all preterm births (PTB) at 22–27, 28–31 and
32–36 weeks of gestation compared with normal BMI pre-
sented as unadjusted (RR) and adjusted relative risks (aRR)
after exclusion of cases with prior preterm birth
Table S2. Factors associated with preterm birth
(<37 weeks) stratified by maternal BMI (kg/m2) &
References
1 March of Dimes. White paper on preterm birth: The global and
regional toll, 2009.
2 Saigal S, Doyle LW. An overview of mortality and sequelae of
preterm birth from infancy to adulthood. Lancet 2008;371:261–9.
3 Hendler I, Goldenberg RL, Mercer BM, Iams JD, Meis PJ, Moawad
AH, et al. The preterm prediction study: association between
maternal body mass index and spontaneous and indicated preterm
birth. Am J Obstet Gynecol 2005;192:882–6.
4 Shaw GM, Wise PH, Mayo J, Carmichael S, Ley C, Lyell DJ, et al.
Maternal prepregnancy body mass index and risk of spontaneous
preterm birth. Paediatr Perinat Epidemiol 2014;28:302–11.
5 Lynch AM, Hart JE, Agwu OC, Fisher BM, West NA, Gibbs RS.
Association of extremes of prepregnancy BMI with the clinical
presentations of preterm birth. Am J Obstet Gynecol
2014;210:428.e1-9.
6 Gould JB, Mayo J, Shaw GM, Stevenson DK, March of Dimes
Prematurity Research Center at Stanford University School of
ª 2016 Royal College of Obstetricians and Gynaecologists
Prepregnancy underweight and risk of preterm birth
Medicine. Swedish and American studies show that initiatives to
decrease maternal obesity could play a key role in reducing preterm
birth. Acta Paediatr 2014;103:586–91.
7 Cnattingius S, Villamor E, Johansson S, Edstedt Bonamy AK, Persson
M, Wikstro €m AK, et al. Maternal obesity and risk of preterm
delivery. JAMA 2013;309:2362–70.
8 Harris G. Study says pregnant women in india are gravely
underweight. The New York Times 2015:A4 (updated March 2015,
cited July 2015]. [www.nytimes.com/2015/03/03/world/asia/-
pregnant-women-india-dangerously-underweight-study.html?_r = 0]
9 Kubota K, Itoh H, Tasaka M, Naito H, Fukuoka Y, Kato KM, et al.
Changes of maternal dietary intake, bodyweight and fetal growth
throughout pregnancy in pregnant japanese women. J Obstet
Gynaecol Res 2013;39:1383–90.
10 Barker DJ. Fetal origins of coronary heart disease. BMJ
1995;311:171–4.
11 Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ,
Bleker OP. Effects of prenatal exposure to the Dutch famine on
adult disease in later life: an overview. Mol Cell Endocrinol
2001;185:93–8.
12 Salihu HM, Mbah AK, Alio AP, Clayton HB, Lynch O. Low pre-
pregnancy body mass index and risk of medically indicated versus
spontaneous preterm singleton birth. Eur J Obstet Gynecol Reprod
Biol 2009;144:119–23.
13 Lyndon A, Lee HC, Gilbert WM, Gould JB, Lee KA. Maternal
morbidity during childbirth hospitalization in california. J Matern
Fetal Neonatal Med 2012;25:2529–35.
14 Martin JA, Osterman MJK, Kirmeyer SE, Gregory ECW. Measuring
gestational age in vital statistics data: transitioning to the obstetric
estimate. Nal Vital Stat Rep 2015;64:1–20.
15 World Health Organization. Global database on body mass index.
[http://apps.who.int/bmi/index.jsp] (updated 2015).
16 Fridman M, Korst LM, Chow J, Lawton E, Mitchell C, Gregory KD.
Trends in maternal morbidity before and during pregnancy in
california. Am J Public Health 2014;104:S49–57.
17 Bodnar LM, Siega-Riz AM, Simhan HN, Diesel JC, Abrams B. The
impact of exposure misclassification on associations between
prepregnancy BMI and adverse pregnancy outcomes. Obesity (Silver
Spring) 2010;18:2184–90.
18 Michels KB, Greenland S, Rosner BA. Does body mass index
adequately capture the relation of body composition and body size
to health outcomes? Am J Epidemiol 1998;147:167–72.
19 Haas JS, Fuentes-Afflick E, Stewart AL, Jackson RA, Dean ML,
Brawarsky PB, et al. Prepregnancy health status and the risk of
preterm delivery. Arch Pediatr Adolesc Med 2005;159:58–63.
20 Whiteman VE, Rao K, Duan J, Alio A, Marty PJ, Salihu HM. Changes
in prepregnancy body mass index between pregnancies and risk of
preterm phenotypes. Am J Perinatol 2011;28:67–74.
21 McDonald SD, Han Z, Mulla S, Beyene J, Knowledge Synthesis
Group. Overweight and obesity in mothers and risk of preterm birth
and low birth weight infants: systematic review and meta-analyses.
BMJ 2010;341:c3428.
22 Linna MS, Raevuori A, Haukka J, Suvisaari JM, Suokas JT, Gissler M.
Pregnancy, obstetric, and perinatal health outcomes in eating
disorders. Am J Obstet Gynecol 2014;211:392.e1–8.
2007