Chen et al.

BMC Pregnancy and Childbirth (2017) 17:237

DOI 10.1186/s12884-017-1412-7

RESEARCH ARTICLE Open Access

The prevalence and risk factors of preterm

small-for-gestational-age infants: a
population-based retrospective cohort
study in rural Chinese population
Shi Chen1, Rong Zhu2,9, Huijuan Zhu1, Hongbo Yang1, Fengying Gong1, Linjie Wang1, Yu Jiang3, Bill Q. Lian4,
Chengsheng Yan5, Jianqiang Li6, Qing Wang7, Shi-kun Zhang8 and Hui Pan1*

Abstract
Background: Preterm birth and small for gestational age (SGA) are strong indicators of neonatal adverse outcomes.
With the growing importance of preterm SGA infants, we aim to evaluate the prevalence and risk factors for
preterm SGA in China.
Method: We analyzed the data of parents and infants from a population-based cohort research of the free
National Pre-pregnancy Checkups Project (NPCP) in rural China. Only singleton live births that occurred
between 24 weeks +0 days and 36 weeks +6 days of pregnancy were included in this study. SGA was
defined as birth weight less than the 10th percentile of the reference birth-weight-for-gestational-age
population. A multiple logistic regression model was built using the statistically significant variables
from the 371 variables in the questionnaire.
Results: A total of 11,474 singleton, preterm, live-birth infants were included. Of the total infants, 317 (2.77%)
were preterm SGA infants. A higher risk of preterm SGA infants was observed among mothers who were on oral
contraceptives (OR: 8.162, 95% CI: 1.62241.072), mothers who had syphilis (OR: 12.800, 95% CI: 1.250131.041), and
mothers with a high eosinophil percentage (OR: 13.292, 95% CI: 1.282135.796). Maternal intake of folic acid at least
3 months before pregnancy (OR: 0.284, 95% CI:0.1240.654) and paternal intake of egg and meat (OR: 0.097,95% CI:0.
0300.315) were protective factors. Compared with North China, the incidence of preterm SGA infants was higher in
South China.
Conclusion: Preterm SGA infants were associated with both maternal and paternal factors.
Keywords: Preterm delivery, Small for gestational age, Folic acid supplementation, Oral contraceptive

Background of the cardiovascular system or other organs, which can

Gestational age and birth weight are two of the most im- have life-long effects on an individual [1]. Preterm birth
portant factors for evaluating the prognosis of infants. is a significant causative factor of infant and child mor-
Small for gestational age (SGA) infants may show a de- bidity and mortality. Preterm birth complications are
crease in their growth due to intrauterine growth restric- estimated to be the second most common cause of death
tion. Limitations in fetal growth affect the development in children under 5 years old [2]. In addition to its con-
tribution to mortality, preterm birth has lifelong effects,
* Correspondence: [email protected] and increased risk of neurodevelopmental disorders and

Equal contributors chronic diseases in adulthood [3]. There is a growing

1
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry
of Health, Chinese Academy of Medical Sciences & Peking Union Medical consensus on the differentiation of preterm SGA from
College, Peking Union Medical College Hospital, No.1, Shuaifuyuan Road, term SGA infants from both the clinical and research
Beijing, Dongcheng district 100730, China perspectives [4]. In particular, preterm SGA infants have
Full list of author information is available at the end of the article

The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 2 of 8

a 1040 times greater risk of dying in the first month of interviews by qualified nurses. Physical examinations and
life than term appropriate for gestational age (AGA) in- biochemical studies were also carried out by medical staff
fants [5]. Further, preterm SGA infants have a relatively at the same time [9].
low body fat percentage and would experience a postna- SGA was defined by a 1995 WHO expert committee as
tal catchup growth. Many epidemiological studies have infants with body weight below the 10th percentile of a
demonstrated that the catch-up growth is associated birth-weight-for-gestational-age, using the gender-specific
with cardiovascular diseases, obesity, hypertension, type- reference population with the local growth standards of Li
2 diabetes, and metabolic syndrome in later life [6]. Few Zhu et al. [10] Zhus neonatal growth standards were de-
studies have evaluated the risk factors of preterm SGA rived from birth weight data obtained from a nationwide
infants [7, 8]. The purpose of present study is to identify neonatology network of 161,420 live births in China from
the risk factors of preterm small-for-gestational age in- 2011 to 2014. Preterm SGA infants in our study were
fants. The knowledge gained from this study will be defined as infants born small for gestational age between
crucial in prevention and treatment of preterm SGA. 24 weeks + 0 days and 36 weeks +6 days of gestation.
The inclusion and exclusion criteria are shown in
Methods Fig. 1. A couple and their children was considered as a
Subjects single subject. We included a total of 11,474 subjects.
A population-based retrospective cohort study was per-
formed on 248,501 couples and their children who were Design and setting
part of the free National Pre-pregnancy Checkups Project Data collection
(NPCP) in 220 pilot counties in 30 provinces in China be- A structured questionnaire was constructed by well-
tween January 2010 and December 2012. The project was trained investigators; the questionnaire included 371
implemented by the Chinese National Health and Family variables from the National Free Preconception Health
Planning Commission and Ministry of Finance with aim of Examination Project [9, 11]. As the adverse effect of
preventing birth defects in China, it is the largest pregnancy preterm large-for-gestational age (LGA) infants is con-
retrospective cohort study of the preconception stage troversial [12, 13], we compared preterm SGA infants
in China. It covered all volunteer couples who planned with preterm non-SGA infants including the preterm
to conceive within the next 6 months. The clinical data AGA and LGA infants. We divided China into North
were collected during the preconception medical exam- and South region by the Qinling Mountain-Huaihe River
ination. Information on socioeconomic background, re- Line and we compared the prevalence of preterm SGA
productive history and history of illness, lifestyle, and infants in both regions. We also assessed the risk factors
dietary habits was carefully collected through face-to-face of preterm SGA infants.

Fig. 1 Participant flow chart

Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 3 of 8

Selection of risk factors Results

The questionnaire involves 19 aspects including baseline Baseline characteristics of SGA and non-SGA
characters of couples, physical examination, laboratory A total of 248,501 infants were recruited in our database,
examination family history of couples etc. We chose the of which 12,164 were preterm infants (5.63%). The pre-
variables with a high data integrity over 80%. Among term neonatal mortality was 1.69% in our study. The mean
these variables, 38 variables were statistically significant weight of 11,474 preterm singleton live-birth infants was
exposures in univariate analysis including education level 3104.87 636.03 g, 6307 infants of them were male
of the parents, maternal preconception intake of nar- (54.97%). Among them, 317 (2.77%) were preterm single-
cotics and paternal second-hand smoking, maternal in- ton live-birth SGA infants. The mean weight of them was
take of eggs and meat, the beginning time of maternal 1778.26 438.58 g, 189 of them were male (59.62%).
intake of folic acid, paternal intake of eggs and meat and 11,157 of them were preterm singleton live-birth non-
paternal intake of vegetables, tense maternal and pater- SGA infants, the mean weight was 3141.73 595.51 g,
nal relationship with relatives and co-workers, paternal 6118 of them were male (54.84%).
exposure to heavy metals, organic solutes and vibrations,
maternal syphilis and Candida infection, maternal drug
use, pet exposure and influenza virus infection during Univariate analysis
pregnancy, maternal medical history of diabetes mellitus The following tables show the risk factors in preterm SGA
(DM), maternal medical history of hepatitis B, maternal deliveries. Table 1 indicates that maternal intake of
oral contraceptive use, maternal family history of neo- narcotics lead to a higher risk of preterm SGA. Nutrition
natal death, paternal hepatitis B vaccination and paternal status is also described in Table 1. Parents who did not
family history of DM, maternal height (meter), maternal consume enough vegetables, eggs or meat were more
weight (kilogram), maternal BMI (kg/m2), maternal red likely to deliver preterm SGA infants, which reflects the
blood cell count (109/L), maternal eosinophil percent- paternal level of essential vitamin and proteins. Starting
age, maternal blood glucose level (mmol/L) and paternal time of maternal folic acid supplement is described in
height. It also included the presence of maternal HBe Table 1. Mothers who used folic acid at least 3 months
antibodies, maternal rubella virus IgG antibodies, ma- before last menstrual period (LMP) had a lower risk of
ternal CMV IgG antibodies, maternal toxoplasma IgG giving birth to preterm SGA infants. We also noticed that
antibodies, paternal HBs antibodies. The folic acid a total of 3701 women (32.6%) in our study did not take
supplementation, the preconception habits and socio- folic acid before or after their pregnancy, even though it is
economic status of the parents were based on self- routinely recommended by their health care providers.
report. The location was classified as North or South Paternal exposure to heavy metals, organic solutes and
region of China by the Qinling Mountain-Huaihe vibrations were associated with a higher incidence of
River Line. preterm SGA. Parental infections were also identified as
important risk factors. Syphilis, Candida infection, rubella
virus infection, CMV infection, toxoplasma infection were
Statistical analysis associated with higher rate of preterm SGA. Hepatitis B is
All risk factor variables were first examined by univar- common in China. Positive maternal HBe antibodies is
iate analysis to assess the importance of each of them associated with higher prevalence of preterm SGA. More-
on preterm SGA. We used chi-square test for analysis over, maternal family history of hepatitis B was associated
of categorical variables, and the Mann-Whitney U test with higher rate in preterm SGA infants while paternal
for analysis of continuous variables with a skewed hepatitis B vaccination was associated with lower rate in
distribution as all of continuous variables were of preterm SGA infants.
skewed distribution in this cohorts examined by Mothers who were taking medications, came into con-
Kolmogorov-Smirnov test. The continuous skewed tact with pets or had influenza virus infection were more
variables were expressed in the form of mid-values likely to have preterm SGA infants. With regard to the
(25th percentile, 75th percentile). When a variable was medical history of the parents, maternal family history of
found to be significant at the 0.1 level, it was entered neonatal death were associated with a higher rate of
into the multivariate model. Stepwise logistic regres- preterm SGA.
sion was used to examine the correlation between risk The Qinling Mountain-Huaihe River Line is an import-
factors and preterm SGA. In logistic regression, ant demarcation line of climate, hydrology, and topog-
p < 0.05 was considered statistical significance. The re- raphy in China [14]. The North China has a lower rate of
sults were presented using the OR and 95% CI values. The preterm SGA rate (1.61% vs. 3.32%). The mean birth
analyses were performed with SPSS (version 19.0; SPSS weight of preterm live-birth was 3188.58 650.67 g in
Inc., Chicago, IL, USA). North China and 3061.78 636.03 g in South China.
Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 4 of 8

Table 1 The univariate analysis of risk factors of preterm SGA Table 1 The univariate analysis of risk factors of preterm SGA
infants (categorical variables) infants (categorical variables) (Continued)
Risk factors Number of SGA Number of P value Paternal tense relationship with relatives and co-workers
Non-SGA
No 261 9403 0.075
Maternal Education years
Low 2 627
0 2 27 0.000
Moderate 4 162
06 19 444
High 0 5
69 181 7743
Paternal exposure to heavy metals
912 71 1713
Yes 4 28 0.011
1216 38 966
No 313 11,489
> 16 1 6
Paternal exposure to organic solutes
Paternal Education years
Yes 5 528 0.006
0 1 13 0.008
No 312 10,989
06 13 337
Paternal exposure to vibrations
69 189 7464
Yes 4 54 0.076
912 70 1922
No 313 11,463
1216 33 1066
Maternal syphilis infection
> 16 0 10
Yes 4 29
Maternal intake of narcotics
No 293 10,656
Yes 4 29 0.012
Maternal Candida infection
No 208 10,782
Yes 2 80 0.003
Paternal second-hand smoking
No 269 10,138
Regular 13 358 0.091
Maternal HBe antibodies
Occasional 90 3732
Positive 31 770 0.024
No 191 6089
Negative 255 9855
Maternal intake of eggs and meat
Maternal rubella virus IgG antibodies
No 9 155 0.045
Positive 136 4114 0.022
Yes 292 10,675
Negative 153 6355
Maternal intake of vegetable
Maternal CMV IgG antibodies
No 10 94 0.000
Positive 79 2312 0.068
Yes 290 10,737
Negative 204 8022
Maternal intake of folic acid from at least 3 months before LMP
Maternal toxoplasma IgG
Yes 73 3448 0.003 antibodies
No 241 7584 Positive 9 148 0.052
Paternal intake of eggs or meat Negative 273 10,190
No 8 125 0.003 Paternal HBs antibodies
Yes 286 10,073 Positive 83 2555 0.077
Paternal intake of vegetables Negative 198 7413
No 5 81 0.094 Maternal medication us after LMP
Yes 289 10,104 Yes 20 274 0.000
Maternal tense relationship with relatives and co-workers No 294 10,758
No 272 10,098 0.000 Maternal pet exposure after LMP
Low 29 597 Yes 11 171 0.018
Moderate 0 143 No 305 10,942
High 2 3
Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 5 of 8

Table 1 The univariate analysis of risk factors of preterm SGA with higher eosinophil percentage (OR: 1.067, 95% CI:
infants (categorical variables) (Continued) 1.0101.127) and women with syphilis infection (OR:
Maternal influenza virus infection after LMP 13.292, 95% CI: 1.282135.796). Frequent intake of
Yes 9 92 0.002
meat and egg of father (OR: 0.097, 95% CI: 0.0300.315)
was found to be a protective factor for infants. Comparing
No 305 11,021
with women who did not use folic acid or started using
Maternal medical history of hepatitis B folic acid after 3 months before LMP, intake of folic acid
Yes 4 51 0.076 from 3 months before LMP (OR: 0.284, 95% CI:0.124
No 299 10,811 0.654) was also a protective factor for preterm SGA in-
Maternal oral contraceptive use fants. It is well accepted that maternal BMI before LMP is
Yes 4 56
related to the rate of preterm and SGA. So we put the ma-
ternal BMI before LMP (OR: 0.945, 95% CI: 0.8281.709)
No 300 10,732
in the regression model although it was not statistically
Maternal family history of neonatal death significant. Moreover, the confidence intervals are wide
Yes 2 4 0.010 for some of the factors in the logistic model may due to
No 300 10,846 the small sample size of preterm SGA.
Paternal hepatitis B vaccination
Yes 66 2980.017
Discussion
Birth weight and gestational age are considered as strong
No 230 7273
predictors of short-term and long-term prognosis of in-
Paternal family history of DM fants. Given the growing attention paid to preterm SGA
Yes 4 47 0.055 infants, our study attempted to determine the incidence
No 292 10,716 of the preterm SGA infants and the risk factors associated
Location with delivering preterm SGA infants.
North 60 3671 0.000
A major strength of this study is its large sample size
and the large number of variables analyzed. To the best of
South 257 7486
our knowledge, this is the most extensive multi-center
study in China to evaluate the risk factors associated with
As expected, the parental weight, height and BMI preterm SGA infants. The large number of variables al-
were associated with preterm SGA as shown in Table 2. lows us to analyze more risk factors than previous studies
The median values were used for risk factors that on preterm SGA infants. The effect of paternal factors on
showed skewed distribution. The maternal weight, preterm SGA infants, for example, the maternal eosino-
height, BMI and paternal height were significantly phil percentage has rarely been reported before.
lower and the maternal eosinophil ratio was higher in This database has several unique features. Compared
preterm SGA group. with earlier study, the mortality rate of preterm infants
in our study (5.63%) was lower than the average rate
Multivariable analysis reported for eastern Asia (7.2% (5.49.0)) [15]. With
Table 3 shows the results of multiple logistic regression economic growth and improvements in perinatal care,
of preterm SGA. Higher risks of preterm SGA infants the neonatal mortality rate has decreased by 59.3% from
were observed among women who took oral contra- 2000 to 2010 in China [16], which could be due to lower
ceptives (OR: 8.162, 95% CI: 1.62241.072), women rate of preterm SGA. With regard to the low prevalence

Table 2 The univariate analysis of risk factors of preterm SGA infants (continuous variables)
Risk factors SGA Median(quartile) Non-SGA Median(quartile) P value
Maternal age 24.00 (22.0027.00) 24.00 (22.0027.50) 0.571
Maternal height (meter) 159.00 (156.00161.00) 160.00 (156.00162.00) 0.081
Maternal weight (kilogram) 52.00 (48.0056.00) 52.00 (49.0057.00) 0.027
Maternal BMI before LMP (kg/m2) 20.32 (18.8922.31) 20.70 (19.3822.38) 0.063
9
Maternal red blood cell count (10 /L) 4.22 (3.904.51) 4.13 (3.804.48) 0.005
Maternal eosinophil percentage 2.00 (0.733.48) 1.10 (0.102.50) 0.017
Maternal blood glucose level (mmol/L) 4.90 (4.395.50) 4.82 (4.305.30) 0.018
Paternal height (meter) 170.00 (168.00173.25) 171.00 (169.00175.00) 0.031
Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 6 of 8

Table 3 Multiple logistic regression of preterm SGA infants folic acid before or during pregnancy, even it is routinely
Risk factors B P value OR 95% C.I. for OR recommended. Considering the large percentage of subjects
Lower Upper were from rural areas with relatively poor nutrition status,
Maternal intake of folic acid 1.257 0.003 0.284 0.124 0.654 we think that health care providers in these areas, in
from at least 3 months before particular, should emphasize on folic acid supplementation
LMP before pregnancy.
Maternal oral Contraceptive 2.100 0.011 8.162 1.622 41.072
use Oral contraceptive
Maternal eosinophil 0.064 0.021 1.067 1.010 1.127 Oral contraceptives use is one of the most popular re-
percentage
versible methods of contraception. However, the adverse
Maternal syphilis infection 2.580 0.030 13.191 1.281 135.796 effects of oral contraceptives on fetal development are
Paternal intake of egg and 2.336 0.000 0.097 0.030 0.315 unclear. Previous studies have reported the association
meat of oral contraceptive use and preterm birth and low
Maternal BMI before LMP 0.056 0.403 0.945 0.828 1.709 birth weight [24, 25]. It should be noted that oral contra-
Constant 1.357 0.401 3.886 ceptive use is rare in China compared to developed
countries; only 1.31% of women who delivered preterm
SGA infants and 0.47% of women who delivered preterm
of preterm SGA infants in the North China, it could be non-SGA infants used oral contraceptives. In contrast, it
explained by the significant difference in body weight was reported that oral contraceptive account for 79% of
and height between the Northern and Southern Han all contraception in America for the same period [26].
Chinese. It also fit the Bergmanns rule as body mass Nonetheless, we observed that the use of oral contracep-
increases with colder climate [17, 18]. The greater tives was associated with preterm SGA infants. A pos-
weight and height of parents in the North could explain sible explanation is that increased levels of estrogen at
the lower incidence of preterm SGA in North China. the time of blastocyst implantation may contribute to an
In our study, we discovered a gender-based difference increased risk of preterm birth, which has been shown
in the incidence of preterm SGA infants in China; in women undergoing fresh embryo-based transfer for
59.62% of preterm SGA infants were male. It has been in vitro fertilization [27, 28]. It is undeniable that oral
reported that boys are more likely to be born before contraceptives have many advantages in birth control
term in a different of populations [19]. A possible and regulating the menstrual cycle, but physicians
explanation is that in preterm infants, the growth- should be aware of its potential side effects of delivering
promoting effect of androgen is not obvious. Moreover, preterm SGA infants.
the male preterm infants were more likely to meet the
preterm SGA criteria, as the weight standard for males Maternal eosinophil percentage
is higher than that for females. Eosinophils have been shown to be a significant cellular
infiltrate of the placenta and uterus, including the infiltra-
Folic acid tion and degranulation of eosinophils in the cervix of
Insufficient periconceptional folic acid intake is associ- pregnant humans [29]. The roles of eosinophils in preterm
ated with a number of birth defects that may also be re- delivery or SGA remains unknown. Elevation of the
lated to genetic and environmental factors before eosinophil level is associated with chronic inflammation
conception or during early pregnancy [20]. Recent study or enhanced immune reactions, which may associate with
has shown that supplementation of folic acid could pro- preterm SGA infants. As the eosinophil percentage is not
tect against preterm birth. This study also suggests that routinely determined in pregnancy, further research needs
the duration of folic acid supplementation may be as to be conducted to explore the relationship between the
important as the dose. The risk of spontaneous preterm eosinophil percentage and pregnancy.
birth was inversely related to the duration of folic acid
supplementation, and was lowest in women who re- Infection of syphilis
ported using folic acid supplementation for more than a Despite being easily detectable and treatable during
year prior to conception [21]. However, it is controver- pregnancy, syphilis remains an important cause of
sial whether folic acid supplementation influence the adverse pregnancy outcomes [30]. Syphilis in pregnancy
incidence of low birth weight or SGA [2123]. In our may lead to severely adverse pregnancy outcome such as
study, taking folic acid supplementation more than abortion, prematurity, neonatal death and congenital
3 months before LMP was associated with a significant syphilis in the newborn [31]. In China, the incidence of
reduction in incidence of preterm SGA. As mentioned congenital syphilis has increased at an alarming rate of
before, 32.6% of the women in this study did not take 71.9% per year from 0.01 to 19.68 cases per 100,000 live
Chen et al. BMC Pregnancy and Childbirth (2017) 17:237 Page 7 of 8

births from 1997 to 2005 [32]. A study released in 2013 Abbreviations

indicated that total incidence of maternal syphilis in AGA: Appropriate for gestational age; DM: Diabetes mellitus; LGA: Large for
gestational age; LMP: Last menstrual period; SGA: Small for gestational age
China was estimated as 0.30% (95% CI: 0.280.32) [32].
In our study, the incidence of maternal syphilis was Acknowledgments
1.35% in women who delivered preterm SGA infants, We thank all the participants in this research and all the medical staffs in the
220 counties for their hard work in NFPC. We also gratefully thank the
which was much higher than the incidence in women valuable support of Xu Ma (National Research Institute for Family Planning,
who delivered preterm non-SGA infants (0.271%). Unless No. 12, Dahuisi Road, Haidian District, Beijing 100081, China), QiaoMei WANG,
testing and treatment of syphilis during pregnancy are HaiPing SHEN and YiPING ZHANG (National health and family planning
commission of the peoples republic of China).
made universally available, over half of the pregnancies in
women with syphilis will have adverse outcome [33]. Funding
Primary prevention and prenatal care are needed to be This study was supported by the Five-twelfth National Science and
Technology Support Program (No.2012BAI41B08, No.2013BAI12B01) and the
addressed to reduce the incidence of syphilis associated National Natural Science Foundation (No.41401469), Peoples Republic of
preterm SGA infants. China.

Availability of data and materials

Nutrition status of father The datasets during the current study are available from the corresponding
author on reasonable request.
Our study showed that diet containing egg and meat of
the father, which reflected the paternal nutritional status, Authors contributions
particularly protein intake, was significantly associated SC data analysis and drafting of manuscript. RZ data analysis and drafting of
manuscript. HZ paper review and analysis of data. HY acquisition and
with lower incidence of preterm SGA infants. Animal
interpretation of data and paper review. FG study design and drafting of
studies have demonstrated that all stages of gamete mat- manuscript. LW technical support, acquisition of data and paper review. YJ
uration and preimplantation embryo development are acquisition and interpretation of data and drafting of manuscript. BQL data
analysis and paper review. CY acquisition and interpretation of data and
influenced directly by parental nutrition and hormonal
drafting of manuscript. JL acquisition of data, technical support and paper
status [34]. Moreover, an animal model showed that the review. QW acquisition of data, technical support and paper review. SZ study
diet during the preconception period and pregnancy of design and paper review. HP paper review and study supervision. All authors
read and approved the final manuscript.
the males and females differentially affects embryonic
growth and fatty acid content [35]. Also, there is an ani- Ethics approval and consent to participate
mal study showed that paternal nutrition can influence The study was approved by the medical ethics committee of the Peking
Union Medical College Hospital. Informed consent was obtained from all
the amount of seminiferous tissue, spermatogenic cap-
NFPC participants.
acity and spermatogenic efficiency [36]. However, our
understanding of the influence of paternal nutritional Competing interests
The authors declare that they have no competing interests.
status on human offspring is still limited.

Publishers Note
Limitation Springer Nature remains neutral with regard to jurisdictional claims in
The primary limitation of our study is that several risk published maps and institutional affiliations.
factors such as the beginning time of maternal folic acid Author details
intake, the paternal intake of egg and meat, and the use 1
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry
of oral contraceptive were based on self-report of the of Health, Chinese Academy of Medical Sciences & Peking Union Medical
College, Peking Union Medical College Hospital, No.1, Shuaifuyuan Road,
parents. More quantitative variables are needed in our Beijing, Dongcheng district 100730, China. 2Intern of medicine, PUMCH,
questionnaire. With the large number of subjects, it is Beijing 100730, China. 3School of public health, PUMC, Beijing 100730, China.
4
difficult to assure the completeness of data. This study University of Massachusetts Medical Center, 55 Lake Ave., North Worcester,
MA 01655, USA. 5Hebei Center for women and childrens health,
identified several factors that are associated with pre- Shijiazhuang 050031, China. 6School of Software Engineering, Beijing
term SGA, due to diverse culture and social economic University of Technology, Beijing 100124, China. 7Tsinghua National
status of these subjects, some confounding factors might Laboratory for Info. Science and Technology, Tsinghua University, Beijing
100084, China. 8Research association for women and childrens health,
be overlooked. Beijing 100081, China. 9Department of Gynaecology and Obsterics, Peking
University First Hospital, Beijing 100034, China.
Conclusion Received: 10 October 2016 Accepted: 5 July 2017
Our results show that preterm SGA infants were asso-
ciated with both maternal and paternal factors.
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