SE M I N A R S I N P E R I N A T O L O G Y ] (2017) ]]]–]]]

Available online at www.sciencedirect.com

Seminars in Perinatology

www.seminperinat.com

Epidemiology of preterm birth

Stephanie E. Purisch, MD*, and Cynthia Gyamfi-Bannerman, MD, MSc
Department of OBGYN, Division of Maternal–Fetal Medicine, Columbia University Medical Center, New York, NY

article info abstra ct

Keywords: Preterm birth is a worldwide epidemic with a global incidence of 15 million per year.
preterm birth Though rates of preterm birth in the United States have declined over the last decade,
prematurity nearly 1 in 10 babies is still born preterm. The incidence, gestational age, and underlying
epidemiology etiology of preterm birth is highly variable across different racial and ethnic groups and
racial disparity geographic boundaries. In this article, we review the epidemiology of preterm birth in the
global health United States and globally, with a focus on temporal trends and racial, ethnic, and
geographic disparities.
& 2017 Elsevier Inc. All rights reserved.

Introduction
Preterm birth, defined as delivery prior to 37 weeks gesta-
tional age, is a worldwide epidemic. The global incidence of
preterm birth is approximately 15 million per year.1 In the
United States, nearly 1 in 10 babies is born preterm. As the
leading cause of neonatal morbidity and mortality, prema-
turity is not only an emotional burden for families but also an
economic burden on society. The societal cost of prematurity
in the United States—accounting for medical costs, educa-
tional costs, and lost productivity—has been estimated to be
at least 26.2 billion dollars each year.2 Length of hospital stays
for preterm infants average 13 days compared to 1.5 days for
term infants, and medical costs for preterm infants in the
first year of life average ten times greater than those for term
infants ($32,325 compared to $3,325).
Preterm birth in the United States
The rate of preterm birth rose steadily in the United States in
the late 20th century, from 9.5% in 1981 to a peak of 12.8% in
2006.3 Rates of preterm birth have fortunately declined over
the last decade. The preterm birth rate reached a nadir of
9.57% in 2014. In 2015, however, the rate of preterm birth was
9.62%—up slightly from the year prior and representing the
first time since 2006 that the United States saw an increase in
the rate of preterm birth.4 It is intriguing to note, however,
that the PTB rate in the 1980s is not vastly different than the
current PTB rate.
Premature infants are at risk of multiple complications, and
neonatal outcomes are closely related to the gestational age
at delivery. As such, preterm birth is further classified as late
preterm birth (occurring between 34 and 36 and 6/7 weeks),
moderate preterm birth (32 to 33 and 6/7 weeks), and early
preterm birth (less than 32 weeks). The majority of preterm
deliveries in the United States occur in the late preterm
period. In 2015, 71.4% of all preterm births (6.87% of all births)
occurred in the late preterm period.4 In the same year, 12.2%
of preterm births (1.17% of all births) occurred between 32 and
33 and 6/7 weeks (moderate preterm birth), and 16.4% of
preterm births (1.58% of all births) occurred at less than 32
weeks (early preterm birth).
Neonatal complications of preterm birth include respira-
tory distress syndrome, sepsis, intraventricular hemorrhage,
necrotizing enterocolitis, hypothermia, hypoglycemia, hyper-
bilirubinemia, and feeding difficulties. Long-term morbidity
includes retinopathy of prematurity, neurodevelopmental
impairment, and cerebral palsy. A recent MFMU study
of contemporary neonatal outcomes demonstrated that,

*
Correspondence to: Department of Obstetrics & Gynecology, 622 West 168th St, PH 16-66, New York, NY 10032.
E-mail address: sp3511@cumc.columbia.edu (S.E. Purisch).

http://dx.doi.org/10.1053/j.semperi.2017.07.009
0146-0005/& 2017 Elsevier Inc. All rights reserved.
2 SE M I N A R S I N
although each additional week of gestation confers a survival
benefit, neonates born later in the preterm period remain at
risk of morbidity.5 The study found that the risk of major
neonatal morbidity (intraventricular hemorrhage grade III/IV,
seizures, hypoxic-ischemic encephalopathy, necrotizing
enterocolitis stage II/III, bronchopulmonary dysplasia, and
persistent pulmonary hypertension) was less than 5% after 32
weeks, but minor neonatal morbidity (hypotension requiring
treatment, intraventricular hemorrhage grade I/II, necrotizing
enterocolitis stage I, respiratory distress syndrome, and
hyperbilirubinemia requiring treatment) still occurred in
51% of neonates born at 34 weeks and in 16% of neonates
born at 36 weeks.
Etiologies of preterm birth
Preterm birth can be further classified as spontaneous pre-
term birth or medically indicated (iatrogenic) preterm birth.
Pathways to spontaneous preterm birth include preterm
labor, preterm premature rupture of membranes, and second
trimester spontaneous pregnancy loss. Approximately two-
thirds of all preterm deliveries are spontaneous.3 Risk factors
for spontaneous preterm birth include prior spontaneous
preterm birth, short cervix, non-Hispanic black race, short
inter-pregnancy interval, multiple gestations, and uterine
anomalies. Prior spontaneous preterm birth is the strongest
risk factor, with recurrence rates ranging from 15% to 50%
depending on the number and gestational age of prior
preterm deliveries.3 Yet spontaneous preterm births also
occur in nulliparous women without identifiable risk factors,
and therefore preventative strategies are limited.
Fig. 1 – Rate of preterm birth o37 weeks gestation by race/ethnicity; results displayed as a percentage of all U.S. live births
from 2012 to 2014.
P E R I N A T O L O G Y ] (2017) ]]]–]]]
Medically indicated or iatrogenic preterm birth encom-
passes a wide-range of maternal and fetal pathologies,
including but not limited to preeclampsia, poorly controlled
diabetes, intrauterine growth restriction, and abnormal pla-
centation. It is estimated that one-third of all preterm
deliveries in the United States are medically indicated.3
Preterm birth disparities
While advances have been made in reducing the burden of
prematurity, there are significant racial and ethnic dispar-
ities. Black race is an established risk factor for spontaneous
preterm birth, and preterm birth rates in the United States are
48% higher among non-Hispanic black women compared to
women of other racial groups.6 From 2012 to 2014, the
average percentage of live births that were preterm was
8.5% for Asian/Pacific Islander women, 9.0% for white women,
9.1% for Hispanic women, 10.4% for American Indian/Alaska
native, and 13.3% for black women (Fig. 1). The rate of
preterm birth among black women rose slightly in 2015 to
13.4%, compared to 13.2% in 2014. Black women in 2015
experienced preterm delivery at earlier gestational ages, with
36% of all preterm births occurring prior to 34 weeks,
compared to 28% for all races.4
The mechanism for these disparities is poorly understood,
and the disparities have persisted in studies that control for
socioeconomic factors. For instance, a population-based
study of births in Missouri demonstrated that black mothers
had a nearly threefold higher rate of preterm birth between
20–34 and 6/7 weeks gestation (relative risk ¼ 2.99, 95% CI:
2.89–3.08).7 After adjusting for socioeconomic factors and
maternal medical comorbidities, black mothers remained at
 SEM I N A R S I N P E R I N A T O L O G Y
increased risk for preterm birth (adjusted OR ¼ 2.21, 95% CI:
2.11–2.31). This same study found that black women were
more likely to experience an early preterm birth between 20
and 28 weeks when outcomes are poorest (relative risk ¼ 3.71,
95% CI: 3.43–4.00). Black women were also more than five
times more likely to experience a recurrent preterm birth
than white women (relative risk ¼ 5.40, 95% CI: 5.06–5.75).
This increased risk persisted when the authors restricted
analysis to a subset of spontaneous preterm births
and adjusted for confounders (adjusted OR ¼ 3.21, 95% CI:
2.70–3.80).
Studies have considered underlying genetic variations
which may contribute to the racial disparities in preterm
birth. Several groups have examined the relationship
between the TNF-2 allele of the tumor necrosis alpha gene
and spontaneous preterm birth. Macones et al.8 found that
carriers of the TNF-2 allele had a twofold greater risk of
spontaneous preterm birth. Interestingly, despite similar
carrier frequencies for the allele, the relationship between
TNF-2 and spontaneous preterm birth was stronger in African
Americans (OR ¼ 2.5, 95% CI: 1.4–4.5) than in Caucasians (OR
¼ 1.6, 95% CI: 0.5–5.2). The association between TNF-2 and
spontaneous preterm birth was further influenced by the
presence of symptomatic bacterial vaginosis, suggesting that
gene–environment interactions are important determinates
of risk. Wang et al.9 also demonstrated a link between the
SERPINH1 gene and preterm premature rupture of mem-
branes in African Americans. The SERPINH1 gene encodes
heat-shock protein 47, which is essential for collagen syn-
thesis. A functional single nucleotide polymorphism (SNP) in
this gene (−656 C/T) occurs more frequently in African
Americans than in European Americans (12.4% vs 4.1%, p o
0.024) and, in a study of over 600 women, the −656 T allele
was found to be significantly associated with PPROM in (−656
T allele frequency 11.5% in PPROM cases vs 4.47% in controls;
p o 0.001; OR ¼ 2.77; 95% CI: 1.73–4.95). Both TNFα and
SERPINH1 show promise as candidate genes for preterm birth
in African Americans but additional research is needed to
better understand causality (if any) and the complex gene–
gene and gene–environment interactions that likely exist.
Trends in U.S. preterm birth rates
Several authors have examined the temporal changes in
preterm birth rates to further understand trends related to
the gestational age and etiology of preterm deliveries. From
1990 to 2005, the preterm birth rate rose 20%, from 10.6% in
1990 to 12.7% in 2005. During this time period, the greatest
increase in preterm deliveries based on gestational age was in
the subgroup of late preterm birth which increased 25% from
7.3% in 1990 to 9.1% in 2005.10
Goldenberg et al.3 found that the increase in preterm birth
between 1989 and 2000 was largely driven by a nearly 50%
increase in medically indicated preterm deliveries during the
time period. The increased utilization of assisted reproduc-
tive technologies with resultant multiple gestations was
another contributor to rising preterm birth rates during that
time.3 Multiple gestations account for a significant percent-
age (15–20%) of preterm deliveries. While multiple gestations
] (2017) ]]]–]]] 3
represent only 3.5% of all live births in the United States, 60%
of twins and up to 95% of triplet and higher-order multiple
gestations deliver preterm. Rates of preterm birth amongst
singleton pregnancies alone are, in comparison, only 7.7%.6
Reddy et al.11 used birth certificate data to further examine
the delivery indications and neonatal outcomes for over
292,000 late preterm gestations between 1990 and 2005. Their
results demonstrated that 49% of all late preterm deliveries
were secondary to isolated spontaneous preterm labor,
whereas 16% had reported obstetric complications and 14%
had reported maternal medical conditions. Highly concerning
was that 23.2% of the late preterm deliveries had no recorded
delivery indication. This subset of deliveries with no recorded
indication was associated with higher maternal age, higher
maternal education level, multiparity, and prior delivery
greater than 4000g. Deliveries without an indication were
more common outside of the Northeast region.
Importantly, the study also demonstrated that from 34 to
39 weeks, there were declining rates of neonatal and infant
mortality with each additional week of gestation. At 34 weeks
gestation, the rate of neonatal mortality was 7.7/1000—yield-
ing a nearly 10-fold higher relative risk of mortality compared
to delivery at 39 weeks gestation. Even at 37 weeks gestation,
the risk of neonatal mortality was twofold higher than that at
39 weeks gestation with rates of 1.7/1000 births at 37 weeks vs
0.8/1000 births at 39 weeks. Given the lack of a documented
medical indication for preterm delivery in many cases, the
authors speculated that patient-driven factors, combined
with an underestimate at the time of the morbidity and
mortality of late preterm birth, may have contributed the
rise in late preterm birth. The results of the study, however,
identified associated increases in neonatal morbidity and
mortality that may not have been justified by the risk of
continued pregnancy in up to 23% of cases.
Between 2005 and 2010, there was mounting evidence that
late preterm birth is associated with not only increased
mortality, but also higher rates of respiratory distress syn-
drome, necrotizing enterocolitis, intraventricular hemor-
rhage, sepsis, and NICU admission compared to term births.
Similar to the Reddy study, Gyamfi-Bannerman et al.12 in
2011 reviewed a cohort of 2693 late preterm births between
2003 and 2007 and assessed the indication for delivery. In this
cohort, 67.6% of late preterm births were due to spontaneous
preterm labor or preterm premature rupture of membranes.
The remaining 32.3% of deliveries were non-spontaneous or
iatrogenic, and the authors examined whether or not the
delivery indications for these births were evidence-based.
The study found that the majority (56.7%) of iatrogenic late
preterm births were for non-evidence-based indications (i.e.,
oligohydramnios, gestational hypertension, mild preeclamp-
sia, or prior classical cesarean/myomectomy). Overall, 18.3%
(494/2693) of all deliveries in the cohort were non-evidence-
based—and potentially avoidable.
In another study, Gyamfi-Bannerman et al.13 reported on
trends in singleton preterm birth between 2005 and 2012, a time
period in which the total singleton preterm birth rate declined
from 9.1% to 7.7%. The authors found a reduction in preterm
birth in all gestational age categories (Fig. 2). There was a 17.1%
decline in early preterm birth, as 12.4% decline in moderate
preterm birth, and a 15.8% decline in late preterm birth. These
4 SE M I N A R S I N P E R I N A T O L O G Y
Fig. 2 – Distribution of U.S. singleton live births by
gestational age, 2005–2012. Temporal changes in the
distribution of deliveries based on gestational age: U.S.
singleton live births, 2005–2012. Rates shown on a
logarithmic scale, were all calculated proportionate to the
index year of 2005. (Adapted with permission from Gyamfi-
Bannerman. Trends in preterm delivery, 2005–2012. Obstet
Gynecol 2014.)
declines were accompanied by an increase in both full term and
late term birth, by 14.3% and 18.7%, respectively. Both sponta-
neous and medically indicated preterm deliveries decreased
during the study time period, however, there was a greater
decrease in the rate of indicated preterm deliveries (17.2%
compared with a 15.4% decrease in spontaneous preterm deliv-
eries). The overall ratio of spontaneous to medically indicated
preterm birth remained constant. However, this study had an
Fig. 3 – Estimated number of preterm births in 2010 worldwide; ranking lists the 10 countries which account for the majority
(60%) of preterm births worldwide.
] (2017) ]]]–]]]
overall greater proportion of medically indicated preterm births
compared to other studies (41–43% vs 30–35%), likely secondary
to the exclusion of multiple gestations which are a significant
contributor to the incidence of spontaneous preterm birth. One
proposed mechanisms for the recent reductions in preterm birth
was the introduction of the “39 weeks rule,” whereby in April
2013, the American College of Obstetrics and Gynecology and the
Society for Maternal–Fetal Medicine, released a statement advis-
ing against non-medically indicated or elective deliveries prior to
39 weeks gestation.14 The utilization of progestogens in women
at risk for spontaneous preterm birth may be a contributing
factor.
Global trends
There is significant variation in the incidence of preterm birth
worldwide. The rates of preterm birth in 184 countries in 2010
ranged from 5% in several Northern European countries to
18% in Malawi.15 Rates are highest in low income and lower-
middle income countries (11.8% and 11.3% on average,
respectively), whereas rates are lower in upper-middle and
high-income countries (9.4% and 9.3%, respectively). More
than 60% of all preterm births worldwide occur in low-
resource, high-fertility countries in sub-Saharan Africa and
south Asia. Amongst high-resource counties, the United
States has the highest incidence of preterm birth and accounts
for 42% of all preterm births in high-resource settings (0.5
million per year in the United States out of 1.2 million total per
year in high-income countries). The United States is, notably,
the only high-income country to rank in the top 10 list for
greatest overall number of preterm births per year (Fig. 3).16
 SEM I N A R S I N P E R I N A T O L O G Y
Our understanding of the causes of preterm birth worldwide,
and specifically the proportion of spontaneous vs iatrogenic
preterm births, is limited by the lack of population-based data
from low- and middle-income countries. In general, medically
indicated preterm births are felt to represent a smaller propor-
tion of preterm births in low-resource countries where there is
limited access to diagnostic tools.16 For instance, whereas con-
ditions such as growth restriction might prompt an iatrogenic
preterm birth in a high-resource setting, the same pregnancy in a
low-resource setting may progress without intervention and end
in stillbirth. Studies of preterm birth at tertiary care centers in
low-resource settings report rates of iatrogenic preterm birth
ranging from 20% in Sudan up to 40% at a teaching hospital in
Ghana, but this data may not reflect the general population.16–18
There are additionally differences in survival rates for
preterm babies born in high-resource and low-resource set-
tings. In high-resource settings, approximately 50% of babies
born at 24 weeks survive, albeit not without significant long-
term disability in the majority of survivors. In low-resource
settings, in contrast, over 90% of babies born at less than 28
weeks will not survive the first week of life and only half of
babies born at 32 weeks will survive.16
Our changing population
The population of childbearing women in the Unites States
continues to evolve and influence the epidemiology of preterm
birth. In 2015, the birth rate for women aged 35–39 was 51.7
births per 1000 women—a 13% increase since 2010. The birth rate
for women aged 40–44 was 11.0 births per 1000 women—a 4%
increase compared to 2014.4 Advancing maternal age, coupled
with the United States obesity epidemic, means that pregnant
women are more likely to have comorbidities that may neces-
sitate an early delivery. Therefore, while indicated preterm
deliveries have declined in recent years, rates may ultimately
plateau (or even rise again) unless there are significant improve-
ments in the general health of our population.
Goals for the future
The March of Dimes' goal is to reduce the incidence of preterm
birth to 8.1% by the year 2020.19 In our efforts to move towards
this goal, it is imperative that we continue to study the under-
lying mechanisms of preterm birth, develop targeted therapies,
and work to eliminate disparities amongst at-risk women.
re fe r en ces
1. Organization WH. Preterm birth: Fact sheet 2016. Available
from: http://www.who.int/mediacentre/factsheets/fs363/en/.
Updated November 2016.
] (2017) ]]]–]]] 5
2. Preterm Birth: Causes, Consequences, and Prevention. In:
Behrman RE, Butler AS, et al., eds. Preterm Birth: Causes,
Consequences, and Prevention. Washington, DC: The National
Academies Collection: Reports funded by National Institutes
of Health; 2007.
3. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology
and causes of preterm birth. The Lancet. 2008;371(9606):
75–84.
4. Hamilton BE, Martin JA, Osterman MJ. Births: preliminary data
for 2015. Natl Vital Stat Rep. 2016;65(3):1–15.
5. Manuck TA, Rice MM, Bailit JL, Grobman WA, Reddy UM,
Wapner RJ, et al. Preterm neonatal morbidity and mortality by
gestational age: a contemporary cohort. Am J Obstet Gynecol.
2016;215(1): 103e1–e14.
6. National Center for Health Statistics, Final Natality Data.
Available from: www.marchofdimes.org/peristats.
7. Kistka ZA, Palomar L, Lee KA, Boslaugh SE, Wangler MF, Cole
FS, et al. Racial disparity in the frequency of recurrence of
preterm birth. Am J Obstet Gynecol. 2007;196(2):131.e1–6.
8. Macones GA, Parry S, Elkousy M, Clothier B, Ural SH, Strauss
Iii JF. A polymorphism in the promoter region of TNF and
bacterial vaginosis: preliminary evidence of gene-environ-
ment interaction in the etiology of spontaneous preterm
birth. Am J Obstet Gynecol. 2004;190(6):1504–1508.
9. Wang H, Parry S, Macones G, Sammel MD, Kuivaniemi H,
Tromp G, et al. A functional SNP in the promoter of the
SERPINH1 gene increases risk of preterm premature rupture
of membranes in African Americans. Proc Ntl Acad Sci. 2006;
103(36):13463–13467.
10. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F,
Kirmeyer S, et al. Births: final data for 2005. Natl Vital Stat Rep.
2007;56(6):1–103.
11. Reddy UM, Ko CW, Raju TN, Willinger M. Delivery indications
at late-preterm gestations and infant mortality rates in the
United States. Pediatrics. 2009;124(1):234–240.
12. Gyamfi-Bannerman C, Fuchs KM, Young OM, Hoffman MK.
Nonspontaneous late preterm birth: etiology and outcomes.
Am J Obstet Gynecol. 2011;205(5):456.e1–e6.
13. Gyamfi-Bannerman C, Ananth CV. Trends in spontaneous
and indicated preterm delivery among singleton gestations in
the United States, 2005–2012. Obstet Gynecol. 2014;124(6):
1069–1074.
14. American College of Obstetricians and Gynecologists. ACOG
Committee Opinion No. 561: nonmedically indicated early-
term deliveries. Obstet Gynecol. 2013;121(4):911–915.
15. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller A-B,
Narwal R, et al. National, regional, and worldwide estimates
of preterm birth rates in the year 2010 with time trends since
1990 for selected countries: a systematic analysis and impli-
cations. The Lancet. 2012;379(9832):2162–2172.
16. March of Dimes P, Save the Children, WHO. In: Howson MK
CP, Lawn JE, et al., eds. Born Too Soon: The Global Action Report
on Preterm Birth. Geneva: World Healh Organization; 2012.
17. Alhaj AM, Radi EA, Adam I. Epidemiology of preterm birth in
Omdurman maternity hospital, Sudan. J Matern Fetal Neonatal
Med. 2010;23(2):131–134.
18. Nkyekyer K, Enweronu-Laryea C, Boafor T. Singleton preterm
births in Korle Bu Teaching Hospital, Accra, Ghana—origins
and outcomes. Ghana Med J. 2006;40(3):93–98.
19. 2016 Premature Birth Report Card. March of Dimes Foundation.
2016:1–3.