REVIEW
Lowering the Premature Birth Rate:
What the U.S. Experience Means for Japan
Akihiko Noguchi

Department of Pediatrics, Saint Louis University, School of Medicine, USA(Received for publication on September 25, 2007)(Revised for publication on October 16, 2007)(Accepted for publication on December 3, 2007)

Abstract: Premature birth rate and low birth weight rate are increasing in industrializedcountries including USA and Japan. The Infant mortality rate (IMR) is three times and 50-75
times greater for infants born at 32-36 weeks and <32 weeks respectively than term-born
counterparts. In the U.S., the IMR is greater than in Japan particularly among black infants
and simply the “lower socioeconomic class” is not the answer. Premature birth is heterogeneous in origin and idiopathic in 70% of the cases. Increased utilization of assisted reproductive technology only accounts for a part of the recent trend. Evidence suggests environmental factors play a significant role, and genetic-environmental interaction is plausible.
A chronic psychosocial stress of pregnant women has been postulated to be modifying theendocrine milieu thereby influencing pregnancy outcomes. In a preliminary observation in
St. Louis, homeless pregnant women with high behavioral and social risks, when accommodated in a shelter home designed for these women, produced significantly less numbers ofpremature and low birth weight infants as compared with the general population. Furthermore, in a randomized controlled study in Washington DC, psychobehavioral intervention
specifically targeting smoking (primary and secondary), intimate partner violence (IPV),and depression among black pregnant women significantly decreased the rate of miscarriage
and low birth weight. These reports may have significant implication to the Japanese situation. Increasing number of Japanese women at reproductive age are exposed to smoking,may have underling psychosocial stress and may suffer from subclinical depression and/orfrom IPV. Detailed epidemiological studies of women before and during the reproductive age
with regard to risk factors can lead to an effective intervention strategy against prematurebirth in Japan. (Keio J Med 57 (1) : 45－ 49, March 2008)
Key words: Premature birth, Low birth weight, United States, Japan, Intervention

While the survival rate of premature infants has been
improving remarkably in the past few decades thanks tothe progress in maternal fetal medicine and neonatology,
premature birth and low birth weight (LBW) still is asignificant issue associated with higher mortality andmorbidity compared with that of full term newborns.
Moreover, a challenge is the increasing rate of prematureand LBW births in developed countries,1, 4 including Japan where the premature birth rate rose from 4.2 % to5.6% and LBW rate rose from 5.6 to 9.4% between 1980

and 2004.5 LBW is defined as birth weight <2500 g andincludes many premature and all the small for gestation
infants. Since birth weight is often the most accurate andreadily available parameter, LBW is used instead of prematurity in many retrospective reports. The infant mortality rate (IMR) is three times and 50-75 times greaterfor 32-36 week and less than 32 week gestational age infants respectively compared with that for term infants.
Among the survivors, morbidity is likewise greater, theless mature they are. Relatively mild premature infants

Presented at the 1524th Meeting of the Keio Medical Society in Tokyo, July 10, 2007
Corresponding Author: Akihiko Noguchi, M.D., MPH 1465 South Grand Blvd. St. Louis Missouri USA 63104 E-mail address:noguchi@slu.edu Tel:(314)577-5642
45

46

Noguchi A: Prevention of prematurity

Fig. Schematic model of interventions for premature birth. Premature birth is directly related to biological process ofpremature uterine contraction. This biological process is influenced by environmental and lifestyle factors that interact to each other.
Interventions target this process and examples of intervention are demonstrated by dotted arrows. Enhancing prenatal care is designed
to identify women early who may benefit from medical interventions such as treatment of infections or hormonal therapy, and provides
personalized psychosocial support, specific education, linking to necessary services etc..

at 33-38 week are nowadays expected to survive over
99%, and the majority of them develop and perform wellat school age. However, as a subpopulation of newborns,
those mild degree premature infants are still at a higher
risk for cognitive deficit and learning disabilities compared with full term counterparts and account for 70% ofprematurity-associated developmental deficit that burdens not only the individual and family but also the community they live in.6, 7 Since 1970s in the United States,
there have been governmental and non-governmental activities to counteract this problem by campaigning to improve the rate of prenatal care for pregnant women, installing the Prematurity Prevention Committee by the Institute of Medicine, inaugurating the NIH Prematurity
Prevention Research Meeting, and authorizing reimbursement for prenatal care by Medicaid (a national insurance program). However, the impact of these activities in the real world is yet to be seen. As the mechanismof labor is not well understood, it is likely that the premature birth and LBW will be with us for awhile.
In the United States, the IMR is higher than that of Japan and the leading cause of infant mortality is congenital birth defects followed by prematurity and LBW.1 If
all the disease conditions associated with prematurity
and LBW are bundled together, the prematurity-related
IMR equals with that due to congenital defects. An important fact with regard to infantile mortality in the United States is health disparities among the race/ethnic
groups. Although this point may sound irrelevant to theJapanese situation, studying the phenomenon can lead tobetter understanding of premature birth in general. The

IMR gap between black and white infants has not been
narrowing over the past few decades.8 This is almost inparallel to the gap of LBW rates between the two populations. The other minority group, Hispanic, has the IMR
similar to whites. This black vs. Hispanic difference
seems to indicate that the high IMR among black infants
is not simply related to the poor social and economical
status per se, since they are both lower and similar compared with whites. Though the offspring of college educated black parents had better figures in the mean birthweight, premature birth rate and LBW birth rate thanthose of the non-college educated black parents, the rates
were still 2-3 times higher than the offspring of whitecollege educated parents.9 Interestingly, the first generation Asian Indians living in California are in general welleducated and in the higher socioeconomic class and yet
their offspring had a higher risk for low birth weightcomparable to blacks,10 again suggesting socioeconomic
class is not the determinant of the LBW rate difference
among race/ethnic groups. Do these data support genetic
factors for prematurity and LBW then? Not entirely.
There is a retrospective study looking at birth weightover three generations longitudinally among different
cultural/ethnic backgrounds from 1956.11 In this study,
there was no difference between the mean birth weightof female infants born to white European new immigrants (first generation) and those to the contemporary
American white residents. The female infants (second
generation) born to the first generation women showedagain no difference in the birth weight between the twogroups nor at the third generation level. The birth weightKeio J Med 2008; 57 (1): 45－ 49

stayed the same over the generations. In contrast, when
the female black offspring of newly immigrated from African or Caribbean countries were compared with thosefrom contemporary American black residents, the birthweight was significantly greater and LBW rate was lower
among the new immigrants at the second generation level. At the third generation level, however, these advantages in the new immigrant group had been lost. The
LBW rate rose and the birth weight declined comparable
to that of the American black resident group. Similar observations have been made in the Mexican immigrants to
the U.S. where the birth weight of the first generation
was greater than that of the second generation.1 2 Thesestudies indicate either acculturation in America, or living
in an industrialized modern society over generations
could negatively influence on the process of pregnancy
and parturition process of these minority populations.
When the birth weight-specific infant mortality rates
were examined, the IMR is lower among blacks compared with whites if a birth weight is less than 2000 g,
e.g. a black infant with a birth weight 1 kg has a betterchance of living compared with a white infant of thesame birth weight and gender. It is clear that the higher
IMR among blacks in the U.S. is not due to their individual higher mortality but rather to their higher rate of
LBW birth rate. Again we face the question of why thehigher LBW rate persists among blacks. Sociologists,public health researchers, obstetricians and pediatricians
predict that it will take some time to find the cause ofthis problem. The causes of premature and LBW birth
are variable and different in each case. Some are known
such as fetal distress, abruptio placenta, pregnancy induced hypertension which necessitate delivery of the fetus to protect the mother and/or fetus, but majority ofpremature births are associated with no known causes.
Williams Obstetrics states that the spontaneous (idiopathic) variety makes up 72% of all premature births.1 3
Among the heterogeneous group of the so called ‘idiopathic’ premature deliveries, there are often associatedrisk factors with premature labor. Such risk factors include 1. Positive history of previous premature delivery,
2. Teenage pregnancy, 3. Short inter-pregnancy period, 4.
Smoking and 5. Psychosocial stress.
Positive history of previous premature delivery : If
the previous pregnancy resulted in singleton delivery at
gestation 29-32 weeks, the odds of producing <35 premature infant in the subsequent delivery is 10 times
higher compared with a case where the previous delivery
was ≥35 weeks. The odds ratio increases to 12.5 times if
the previous delivery was 29-32 weeks gestation.14
Teen age pregnancy: Birth rates for premature infant
and LBW are higher for teenage women. The risk ishighest if the mother is 14 years old or younger. However, the total number of premature births born to the women of this age group in the U.S. is relatively small.15 The

47

number of total premature infants born to the 15-19 year
age group is higher and so is the social impact.
Short pregnancy interval: It is intuitively acceptedthat the uterus needs an adequate recuperating period before the next pregnancy. Indeed the risk of preterm or
LBW delivery is significantly higher among the blacks if
the interval is less than 6 months. Similar phenomena areobserved for whites also when the interval is only 3months.16
Smoking: There are a few theories to explain the association between smoking exposure and low birth weight.
To have the best outcome of pregnancy, the condition of
the women’s body should be prepared best for carrying a
fetus. The vasoconstrictive and other adverse effects of
nicotine and other substances in tobacco are consideredcounteractive. Evidence is accumulating to indicate thateven second handed smoking is hazardous to pregnancy.17
Psychosocial stress: This is an intense area of investigation in relation to premature and LBW delivery. Cooper et al. demonstrated in a prospective study that maternal education level and the degree of stress determinedby a scoring system were associated with a higher premature birth rate.18 College educated black parents experienced a greater incidence of premature infants thantheir white counterparts, as I quoted above. Those data
can be interpreted in this psycho stress model as black
couples expending more family resources than whitefamilies. They could have been exposed to greater stressto attain the same level of life style, negatively impacting
on the pregnancy outcomes. Biological functions age
with stress like body function wears down when it is exposed to harsh weather conditions for a long period oftime. This ‘weathering hypothesis’ states that long term
unconscious stress ages the body function through theendocrine mechanisms by changing pituitary-adrenal andpituitary-gonad axis which then directly and/or indirectly
affects the pregnancy states and parturition mechanism.19
If this is true, an intervention strategy can be constructedaccordingly.
Experience in the United States: The figure outlines
possible biological and environmental factors contributing to LBW/premature births and areas of intervention.
Known causes of premature births sometimes can be intervened such as with 17-α-hydroxyprogesterone forwomen with recurrent miscarriages/premature births ortreatment of infection during pregnancy. For those women with ‘idiopathic’ premature labor, no preventive measure has been instituted in a large scale systematically.
Thus the impact of an intervention on the birth outcomesin a community has not been tested. Olds has shown thatprofessionally trained nurse visits to underserved pregnant women was effective in improving the birth weightaverage compared with home visits by specially trained
lay persons.20 The concept of this intervention is incor-

48

Noguchi A: Prevention of prematurity

Table 1. Premature and LBW rates among infants born tohomeless women at the Our Lady’s Inn, a shelter home in St. Louis.
<2500 gSt. Louis City*
Black
White
All races
National§
Black
White
All races
St. Louis shelter home

Table 2. Birth outcomes in the integrated psycho-behavioral
intervention group compared with the usual care (control) groupin Washington DC.

<37 weeks

14.7
7.4
11.9

22.9
13.1
19.2

13.7
7.2
8.1

17.9
11.5
12.5

9.7

9.7†

The 123 homeless women admitted to the shelter home from 2003 to2006 and whose infants’ birth weight was available were analyzed.
None of the maternal characteristics differed from those women whose
infants’ birth weight was not available (not shown). Eighty percent of
the women were black. *:2003–2006 cumulative data from Missouri
Department of Health and Senior Services, §:2004 data from National
Center for Health Statistics. †: different compared with St. Louis blackor all races p<0.01.

Pregnancy outcomes
Miscarriage
Premature <37 week
Premature <34 week
LBW <2500 g
VLBW <1500 g

Intervention(n=430)
1.4%
12.6
2.0
12.2
0.6

Usual care(n=441)
4.8%
14.3
5.4
14.1
2.8

p-value
0.04
0.53
0.15
0.45
0.03

Pregnant black women (n=1044) with at least one of the four ‘risk
factors’-- smoking, secondary smoking (environmental tobacco
exposure), victim of intimate partner violence and depression-- wererandomly assigned to either integrated intervention counseling or usual
care group. The intervention is composed of maximum 8 counselingsessions during the pregnancy. The figures are from the reference 24.

vention group was provided with educational and counseling sessions by trained black professionals up to 8
times during the pregnancy period specifically targeting
primary smoking, secondary smoking, intimate partner
porated in ‘Enhancing Prenatal Care’ in the figure de- violence and depression. Many of the women had morescribing possible areas for intervention. Enhancing pre- than one of these risk factors. For various reasons, thenatal care here includes: Better collection of information sessions were given to the participants variably 1-8 times
from women particularly with regard to lifestyle, system- because of the participants’ conditions. Nonetheless, theatic and tailored instruction/communication at appropri- intervention group was associated with significantly low
ate intervals, timely linking to necessary services and miscarriage and low birth weight rates compared withagencies where indicated, etc.. In the city of St. Louis in the control group. The importance of the study is that
the Missouri State, USA, there are 3 shelter homes for they identified that at least four specific elements can bepregnant women. Those women are 84% black women, targeted in a larger scale.
Application to Japan: Japanese IMR is one of theassociated various high risk lifestyle factors including
lowestin the world and the premature birth and LBW
drug addiction (42%), history of sexually transmitted
rates
are
significantly lower than the U.S. Japanese peodiseases (35%), victims of domestic violence (46%), victims of sexual abuse (31%) and victims of incest (13%). ple are relatively homogeneous, well educated and mostSheltered pregnant women are in general associated with ly accessible to medial facilities, and health disparities
higher premature birth and LBW rates compared with the seem far less common compared with the U.S.. Data
same socioeconomic and ethnic/cultural counter generated from a trial to further improve in gestationalparts.2 1, 2 2 We have examined the birth weight of new- age and birth weight outcomes in Japan would be veryborn infants born at one shelter home since 2003. 2 3 helpful to the other industrialized countries. What are theSome of the women left the shelter home and informa- contributing factors to the rising premature rate in Japan?
tion was not available. For those whose infant’s birth Assisted reproductive technology (ART) is advanced inweight is known, the premature birth rate showed a bet- Japan and contributes to the increase in multiple pregter trend than the city and the national averages despite nancies and thus premature and LBW births to some exadverse life conditions (Table 1). This shelter home pro- tent. However assuming the rate of ART involved birth atvides free food and board, nursing care and mental health 0.1% in Japan, even with the disproportionately highcare when indicated. Though this is a preliminary obser- premature and LBW rates, the rising rates cannot be exvation, the result is encouraging and supports the Olds’ plained by ART alone. Among the risk factors associatedtheory that assistance by professional personnel of indi- with ‘idiopathic premature deliveries’, smoking and psygent pregnant women produces a better birth weight out- chosocial stress might be reasonable target areas for an
come for even highly stressed women. In Washington, intervention in Japan because of the size of the populaDC, El-Mohandes et al. recently conducted a prospective tion involved and proven causality. The population atrandomized controlled study (RCT) where nearly 3000 tributable risk of maternal smoking to LBW was 7.4% inhigh risk black pregnant women were recruited and 1044 2000 in Japan.4 The statistics by the same group at theeligible individuals were studied (Table 2).24 The inter- National Institute of Public Health in Japan indicates that

Keio J Med 2008; 57 (1): 45－ 49

the smoking rate among pregnant women in Japan is approximately 30% for teenage women and 21% at 24
years old.2 5 These figures are likely underestimated because secondary exposure from smoking partners’ was
not included. The prevalence of women with stressful
lives may be even higher. That stressful life soon afterconception is associated with a higher miscarriage rate.26
This particular study implies that this outcome may havebeen already determined by the time pregnancy is diagnosed. Indeed, to address smoking and psychosocial
stress, epidemiological data are needed such as co-morbidities and lifestyles by interviewing and examining
women during preadolescent and adolescent periods,
pre-pregnancy and inter-pregnancy periods in addition toa gestational period. Taking such a step is a huge task
and of complex design and requires exorbitant resources.
Maternal fetal medicine and neonatology made a progress and will continue to improve the birth outcomes ofprematurity. However, to have a significantly larger impact on the reproductive outcomes at the national level inJapan, USA or any other industrialized country, there
needs to be a proactive strategy. Accurate data can leadto effective intervention programs. It will require cooperation among obstetricians, pediatricians, and professionals from disciplines such as public health, social science,social work, nursing, policy making, and industry. The
group would have to work cohesively and consistently
for data collection, implementation and maintenance ofprograms.
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