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Neonatology
Original research
Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study
  1. Shuting Song1,
  2. Zhicheng Zhu1,
  3. Weiying Mao1,
  4. Yan Zhu1,
  5. Rong Zhang1,
  6. Xinghe Bu1,
  7. Heqin Li2,
  8. Yanqing Han3,
  9. Yuntao Cao4,
  10. Yuan Gao5,
  11. Yin-Ping Qiu6,
  12. Guangyou Wei7,
  13. Pingping Zhang8,
  14. Jijian Xie9,
  15. Min Wang10,
  16. Chao Chen1,
  17. Li Zhu1
  1. 1Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
  2. 2Department of Neonatology, Baoji Maternity and Child Care Hospital, Shanxi, China
  3. 3Department of Neonatology, Sichuan Provincial Maternal and Child Health Hospital, Sichuan, China
  4. 4Department of Neonatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
  5. 5Department of Neonatalogy, Jinhua Woman’s and Children’s Hospital, zhejiang, China
  6. 6Department of Neonatology, General hospital of Ningxia medical University, Yinchuan, China
  7. 7Department of Neonatology, The People’s Hospital of Bozhou, Anhui, China
  8. 8Department of Neonatology, Tianjin First Central Hospital, Tianjin, China
  9. 9Department of Neonatology, Affiliated Taihe Hospital of Hubei University of Medicine, Hubei, China
  10. 10Department of Neonatology, Yichang Central Hospital, Hubei, China
  1. Correspondence to Dr Li Zhu; zhuli_2023{at}126.com

Abstract

Background With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them.

Methods In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases.

Results We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins.

Conclusion We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

  • neonatology

Data availability statement

Data are available upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjpo-2024-002502

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Currently, the growth curves by gestational age established in many countries lack data for extremely preterm infants (EPIs).

    WHAT THIS STUDY ADDS

    • We establish growth curves of single and twin EPIs in China and the USA, respectively

    • There was no significant difference in birth weight for single and twin EPIs with the same sex and gestational age between China and the USA, respectively.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • This study provided theoretical support for assessing the growth of EPIs.

    Introduction

    Birth weight (BW) is an important indicator of fetal intrauterine growth and development and can predict mortality and morbidity. Newborns are categorised based on the relationship between gestational age (GA) and BW: small for GA (SGA, BW <10th percentile for expected in utero growth), appropriate for GA (AGA, BW between the 10th and 90th percentiles for expected in utero growth) and large for GA (LGA, BW >90th percentile for expected in utero growth). SGA infants are at risk for future short stature, neurodevelopment and cognition dysfunction, polycystic ovary syndrome, abdominal adiposity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome risk.1 2 In comparison to AGA infants, LGA infants are at risk for overweight and obesity, hypertension and metabolic syndrome.3 Identifying high-risk newborns with abnormal growth effectively and accurately plays an important role in prognosis assessment and early intervention.

    INTERGROWTH-21st Newborn Cross-Sectional Study charts and the 2013 Fenton growth curve were widely used in the world.4 5 However, there are racial differences in the distributions of BWs and mean BWs.6 Growth curves for single and twin births based on the Chinese population have been established, but extremely preterm infants (EPIs) were not included in some studies.7 8 Zhu and colleagues constructed growth curves for singletons with a GA of 22–42 weeks from 58 hospitals in 23 provinces, but the number of EPIs was limited.9 Additionally, a study from Taiwan established that BW percentages by GA for twins included a small sample of EPIs.10 Although the Fenton curve is widely used,5 the population contained in this study was before 2013. The improvement of the economic level leads to changes in living standards and dietary structure, which may have a certain impact on the BW of the fetus. Moreover, with the advancement of assisted reproductive technology (ART) and neonatal intensive care units (NICUs), the birth rate and survival rate of EPIs have increased significantly. It is extremely important to properly assess the growth of EPIs and guide their management. Therefore, it is necessary to establish growth curves for EPIs.

    We aimed to establish the BW percentile curves by GA and sex for singletons and twins aged 22–27 weeks by analysing the data from 31 provinces from 2010 to 2019, as a supplement to the current growth curves of EPIs in China. Additionally, the National Vital Statistics System (NVSS) data was also analysed. Then, we compared the results from two databases to determine the differences in the birth weights of EPIs between China and the USA.

    Methods

    Study design

    This was a retrospective study; data collection started in April 2020, and the study spanned from 1 January 2010 to 31 December 2019. All infants with GA less than 28 weeks were from 31 provinces, autonomous regions and municipalities. The study involved 68 tertiary NICUs, about 10% of those in mainland China. Of these, 35 were general hospitals, 12 were paediatric hospitals, and 21 were maternity hospitals. As local NICU representatives, they have experience in multicentre clinical research. Additionally, 150 EPIs from the Children’s Hospital of Fudan University from 1 January 2020 to 1 January 2021 were included to add to the number of neonates. The research centre was the Children’s Hospital of Fudan University, which was responsible for coordinating, integrating information and analysing data. The data for the USA was obtained from the NVSS database. This database includes birth records that are submitted electronically by all 50 states and the District of Columbia. The National Centre for Health Statistics gathers information on live births from birth certificates and allows its use in medical research without the need for ethical review or informed consent. For this study, we focused on neonates born between 2016 and 2021 whose birth details and health information were recorded in the NVSS.

    Data collection

    Information collected included GA, BW, sex, singleton or twin. EpiData V.3.1 was used to store data, which can check logical consistency and data verification. The GA was calculated in exact weeks combined with the mother’s last menstrual period (LMP) and pregnancy ultrasound assessment within the first trimester. If the estimated differences were less than 1 week, the LMP assessment was used. Otherwise, the early pregnancy ultrasound assessment was employed. BW was measured within 12 hours of birth using a neonatal electronic weighing scale to the nearest 1 g and taken three times, and the mean measurement was recorded in cases of differences. Multiple pregnancies were also recorded, regardless of the order and type of the twins. The population included in our study were live newborns ranging from 22+0 to 27+6 weeks’ GA, and they were divided into six groups by one complete week.

    Statistical analysis

    Using the generalised additive models for location scale and shape approach to construct the reference values for percentiles (the 3rd, 10th, 25th, 50th, 75th, 90th and 97th) of BW and growth curves for male and female neonates by different GAs. This approach is highly flexible as it relaxes the traditional distributional assumptions about normality to include even highly skewed and kurtotic distributions. It extends not only to the model mean but all other parameters (SD, skewness and kurtosis) of the distribution as linear, non-linear or smoothing functions of explanatory variables (GA). In our study, we used the LMS method with a specific distribution of (μ, σ, υ and τ) and Box-Cox t to model BW. Based on the Akaike information criterion and Bayesian information criterion, the optimal model was determined. Moreover, the proportions of the measured values under the fitting curve, the worm diagram and the Q-Q diagram were used to further evaluate the advantages and disadvantages of the model fitting. The baseline data were analysed using descriptive statistics in EXECL 2019, SPSS V.26.0 and R V.3.1.2. Values in tables with decimal parts are rounded off.

    Results

    In the Chinese database constructed by this study, there were 5536 EPIs, with 64.5% being male and 36.5% being female. Furthermore, 3232 twins were included, of which 40.6% were female and 59.4% were male. The average BWs corresponding to each GA are shown in online supplemental table 1. For the same GA, the mean BWs of males were 17–48 g and 4–52 g higher than those of females in singletons and twins, respectively. GA increased by 1 week, and the average BW of males in singletons increased by 61–161 g and 42–165 g in females. For twins, the average BW increased by 98–101 g in males and 55–121 g in females.

    Supplemental material

    In the NVSS database, there are a total of 97 329 EPIs; 47.2% were female, and 52.8% were male. In addition, there were 24 604 twins, 47.8% of whom were female and 52.2% were male. For the same GA, the mean BWs of males were 32–69 g and 31–72 g higher than those of females in singletons and twins, respectively. GA increased by 1 week; the mean BWs of males in singletons increased by 89–124 g and 80–113 g in females, with 90–127 g increased for males and 82–114 g for females in twins.

    Growth curves of EPIs in China

    The smoothing-fitted centile curves for BW from 22 to 27 weeks of GA for boys and girls in singletons are presented in figure 1A,B. The percentiles of BW by GA between boys and girls for singletons and twins are shown in table 1. Similarly, the growth curves of boys and girls for twins are shown in figure 1C,D. A comparison of the 50th percentile of BW by GA is shown in figure 2. There were slightly higher BWs in males than females for both singletons and twins (figure 3A,B). When the GA was greater than or equal to 24 weeks, male singletons had slightly higher BW than twins did (figure 2C). Interestingly, we found that the curves of the 50th percentile of BW for females were similar for both singletons and twins (figure 2D). The parameters of the selected optimum model in the China and US databases are shown in online supplemental table 4.

    Figure 1
    Figure 1

    The percentile curves of birth weight by gestational age for different sex in singletons and twins in China. (A) Boys growth curve in singletons in China. (B) Girls growth curve in singletons in China. (C) Boys growth curve in twins in China. (D) Girls growth curve in twins in China.

    View this table:
    Table 1

    Reference values of birth weight percentiles by GA for singletons and twins in China

    Figure 2
    Figure 2

    Comparison of the 50th percentile of birth weight by gestational age in China. (A) Comparison of boys and girls in singletons. (B) Comparison of boys and girls in twins. (C) Comparison of singletons and twins for boys. (D) Comparison of singletons and twins for girls.

    Growth curves of EPIs in the USA

    The percentile values of BW by GA between boys and girls for singletons and twins are shown in table 2, respectively. Similarly, the growth curves of males and females for singletons and twins are shown in figure 3. The same phenomenon also existed in the US database, that is, the 50th percentile curves for males were slightly higher than females (figure 4A,B), both in singletons and twins, with a statistical significance (shown in online supplemental table 1). Not only did we find that the 50th percentile curves of BW for females were similar in both singletons and twins, but this phenomenon was also observed in males (figure 4C,D).

    View this table:
    Table 2

    Reference values of birth weight percentiles by GA for singletons and twins in the USA

    Figure 3
    Figure 3

    The percentile curves of birth weight by gestational age for different sex in singletons and twins in the USA. (A) Boys growth curve in singletons in the USA. (B) Girls growth curve in singletons in the USA. (C) Boys growth curve in twins in the USA. (D) Girls growth curve in twins in the USA.

    Figure 4
    Figure 4

    Comparison of the 50th percentile of birth weight by gestational age in the USA. (A) Comparison of boys and girls in singletons. (B) Comparison of boys and girls in twins. (C) Comparison of singletons and twins for boys. (D) Comparison of singletons and twins for girls.

    Comparison of BW percentiles in China and the USA

    Finally, we compared the results from China with the results from the USA and found that among singleton live births, for both male and female EPIs, the average BW and 50th percentile BW in China were slightly higher than those in the USA (figure 5A,B). However, there was no significant difference in male twins between China and the USA (figure 5C). For female twins, the 50th percentile BW was slightly higher than in the USA (figure 5D). All of the statistical analysis results are shown in online supplemental tables 2 and 3.

    Figure 5
    Figure 5

    Comparison of the 50th percentile of birth weight by gestational age between China and the USA. (A) Comparison of China and the USA for boys in singletons. (B) Comparison of China and the USA for girls in singletons. (C) Comparison of China and the USA for boys in twins. (D) Comparison of China and the USA for girls in twins.

    Discussion

    The 2013 Fenton curves5 are now used to assess the growth and development of neonates in our hospital, but there are differences in the physical development of newborns between different populations and races,11 and it is not appropriate to use the same standard for Chinese neonates. Developing ethnicity-specific references for BW is vital. With the improvements of ATR and NICUs, the prevalence of twin pregnancies has significantly increased, and the prevalence of births of smaller GA infants has also increased.12 13 Many growth curves for the Chinese population have gradually been established,7 14 15 and growth curves for twins have been developed.8 10 16 However, these studies mostly concentrated on single live births over 25 weeks of GA, and the sample size for low GA is limited. Furthermore, few studies assessed secular trends of BW in twins and singletons simultaneously in the same period. To better assess the physical development of preterm infants, premature babies at a younger GA need to be included, and growth curves for twins in the same period also need to be established. Currently, there has been no research comparing the gender differences in growth curves for singletons and twins using concurrent data in China. This paper presented sex-specific singleton and twin BW references between 22 and 27 weeks of gestation, based on a cross-sectional study of China from 2010 to 2021. The present study involved 31 provinces in China, and we believe that these data are representative of the entire Chinese population, which can supplement the existing growth curves for EPIs. Moreover, growth curves for EPIs in the USA were also established, and the differences between China and the USA were compared. However, it is important to note that percentile charts do not represent fetal growth standards in utero but rather weight at birth. The following main points emerged from analyses and comparisons of the two databases in China from 2010 to 2021 and in the USA from 2016 to 2019.

    First, our study agreed with the observation from previous studies that girls are born lighter than boys across different populations.7 17 The difference in BW between boys and girls implies that the sexes respond differently to nutritional stimuli, probably due to genetic reasons. The sex difference in BW indicates a reduced fetal response to insulin in female subjects compared with male subjects, attributed to sex-specific genes influencing insulin sensitivity.18 In other words, girls are notably more resistant to insulin than boys.

    A study by Dai et al7 showed that the 50th percentile of BW by GA was lower for newborns than those born in India, Europe and the USA. However, our research found that the median BW of male and female infants with a GA of less than 28 weeks in singletons is higher than that of the USA. A similar trend also existed in female twins, while male twins are basically consistent in China and the USA. In this study, 0.5% of newborns with a BW of <500 g were included in the Chinese database, whereas approximately 11.3% were included in the US database, which may be one of the reasons why the mean BW in China was higher than that in the USA. In addition, the mean BW in this study was in China. Therefore, to further explore changes in BW, a larger sample of EPIs is necessary. In addition, in terms of the Chinese population, our research revealed that the average BWs for EPIs were higher than the research by Zhu.9 We have to acknowledge that China’s economic level has developed rapidly in recent years, and people’s living standards and dietary structure have undergone tremendous changes.

    Furthermore, we found an interesting phenomenon: the growth curves basically coincided when comparing the 50th percentile of BWs of singleton and twin births for the same sex, and this phenomenon was shown in both databases. A study conducted on twins in China revealed that the average BW of twins is lower than that of singletons at all GAs, with a difference of less than 130 g before 35 weeks.19 Another study by Buckler and colleagues found that the average BW of singletons was 100 g greater than that of twins at 24 weeks GA.20 However, Min and colleagues found no significant difference in BW between twins and singletons before 36 weeks of GA21; our findings supported the above conclusion. Additionally, with the increasing research on the growth curves of twins, many people are further exploring whether there is a difference in BW between the types of twins. Monochorionic twins were found to weigh less at birth than dichorionic twins,22 but a recent study indicated that dichorionic twins exhibited faster growth compared with monochorionic twins.23 Chorionicity-specific BW reference charts for dichorionic diamniotic and monochorionic diamniotic twin pregnancies were constructed by Briffa and colleagues.24 Based on the above research, it is extremely important not only to establish the growth curve for twins but also to delve deeper into the growth patterns of different types of twins.

    The limitations of the present study should be noted. First, the study included a large time span of data from 2010 to 2021. During this period, there are changes in the dietary habits and nutritional environment of the pregnant woman, which may have an impact on the BW of newborns. Second, the growth curves for twins established in this study did not distinguish the birth order of the twins or the type of twins. Third, compared with the data sample from the USA, the population included in China was relatively small, which may affect the results of the comparison. Understanding this, we have set ourselves the goal of creating growth curves based on more growth data from China in the future.

    Conclusion

    In conclusion, this study analysed the data of EPIs in China and the USA and established BW growth curves for singletons and twins of different sex. A comparison of the 50th percentile BW growth curves revealed that BWs in male infants were higher than female infants among EPIs. There was no difference in BW between single and twin births for males and females. This study provides a reference for the growth curve of an EPI.

    Data availability statement

    Data are available upon reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    In our study, the study section in China was approved by the research ethics board of the Children’s Hospital of Fudan University, and informed consent was waived due to the retrospective and observational nature of the study (No. 2020 (181)). In the US study section, the National Centre for Health Statistics collects information on live births from birth certificates and authorises its distribution for use in medical research without going through an ethical review or obtaining informed consent.

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    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • Contributors Study concept and design: SS, ZZ, WM, YZ, RZ, XB and LZ. Data acquisition or data analysis/interpretation: SS, LZ, HL, YH, YC, YG, YQ, GW, PZ, JX and MW. Literature research: SS, CC and LZ. All authors contributed to the article and approved the submitted version. SS is the guarantor and accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.