Secular trends of low birth weight, preterm birth, and small for gestational age in Shanghai from 2004 to 2020: an age-period-cohort analysis

Abstract

Background: Although highly heterogeneous among countries, the incidence rates of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) have been increasing globally over the past two decades. To better understand the cause of the secular trends, this study aimed to clarify the effects of age, period, and birth cohorton adverse birth outcomes in Shanghai.

Methods: Data of 2,958,695 singleton live births at 24-41 gestational weeks between 2004 and 2020 were obtained for this study. Age-period-cohort models based on Poisson regression were used to evaluate the independent effects of maternal age, delivery period, and maternal birth cohort on the trends in LBW, PTB, and SGA.

Results: The incidence rates of LBW, PTB, and SGA were 2.9%, 4.7%, and 9.3%, respectively, and significant changes were observed (+6.2‰, +6.1‰, and -11.0‰, respectively) from 2004 to 2020. Cohort effect increased steadily, from 1960 (risk ratio [RR] = 0.71, 95% confidence interval [CI]: 0.65-0.78) to 1993 (RR = 0.97, 95% CI: 0.94-1.01) for LBW and from 1960 (RR = 0.69, 95% CI: 0.64-0.75) to 2004 (RR = 1.02, 95% CI: 0.94-1.12) for PTB. A strong cohort effect was found with the highest risk of SGA (RR = 1.82, 95% CI: 1.72-1.93) in 1960 and the lowest risk (RR = 0.57, 95% CI: 0.54-0.61) in 2004, compared with the reference cohort of 1985. There was a “U-shaped” maternal age effect on LBW and PTB and a weak period effect on the three birth outcomes.

Conclusions: Our findings suggest a significant independenteffect of age, period, and birth cohort on the three birth outcomes. The increasing rates of LBW and PTB inspired us to focus on young and advanced pregnant women. Meanwhile, the prevalence of SGA decreased steadily, illustrating the need for further research on the mechanisms underlying these trends.

Background

Adverse birth outcomes (ABOs), including low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), are the leading causes of neonatal mortality and morbidity in young children. Numerous studies reported ABOs as a significant global public health problem over the past two decades. It was estimated that 12 million PTB and 32 million SGA babies were born in sub-Saharan African and South Asian countries, accounting for most of global ABOs [1, 2]. PTB rates were reported to be approximately 5% in Europe and 18% in Africa [1]. Kaforau et al. also estimated the mean prevalence rates of LBW and PTB in 11 countries in the Pacific region to be 12% and 13%, respectively [3]. South Asia has the highest rate of SGA, where 40% are categorised as SGA [4]. These findings have shown that ABOs mainly occurred in low- and middle-income countries and that ABO incidence rates are highly heterogeneous worldwide [1, 4].

LBW, referring to a birth weight < 2500 g, is a valuable marker of immaturity at delivery. PTB, mostly defined as birth before 37 completed weeks of gestation, commonly leads to neonatal mortality and morbidity [5]. SGA means the birth weight falls below a gestational age and sex-specific cut-off point, which is commonly the lowest 10th centile or 2 standard deviations (SDs) below the average [6, 7]. Therefore, SGA can be considered a retrospective indicator of intrauterine growth restriction. Infants born with ABOs are at an increased risk of respiratory distress syndrome, stunting, mental retardation, and early childhood mortality [4].

Since the Reform and Opening up in the 1990s, Chinese people have undergone a dramatic economic and nutritional transition [8]. Along with changes in lifestyle and dietary patterns, the epidemiology of ABOs has also changed [9]. These changes may contribute to the future burden of chronic diseases, given the potential risks of fetal growth restriction. Previous studies have established how maternal age has a “U-shaped” effect on ABOs [10, 11]. Although studies have examined secular trends in PTB and LBW in China, these analyses used either age or period as an additional factor. Age-period-cohort (APC) analysis is a classic model used to demonstrate trends in health outcomes because it can simultaneously examine the effect of maternal age (age effect, defined as variations caused by physiological changes and social status changes) [12], delivery year (period effect, representing a set of social events and environmental factors such as medical technology and public health policies before outcomes), and maternal birth year (cohort effect, reflecting individual experience and exposure factors during their lifetime). To better understand the changes in ABOs, this study aimed to clarify the effects of maternal age, period of delivery, and maternal birth cohort on trends in LBW, PTB, and SGA in Shanghai.

Methods

Results

The maternal and neonatal characteristics of the study population according to the delivery period are presented in Table 1. We included 295,8695 singleton live births, of which 52.9% were males and 47.1% were females. Maternal age at childbearing increased significantly, with a mean age of 26.9 years in 2004, which increased to 30.1 years in 2020. The percentage of highly educated mothers increased over time, whereas the proportion of multiparous mothers increased from a quarter to more than a third. However, there was no clear trend of change in birth weight during this period, although a very small decrease was observed.

The overall prevalence rates of LBW, PTB, and SGA were 2.9%, 4.7%, and 9.3%, respectively, from 2004 to 2020. After standardisation, significant changes remained in the trends in LBW, PTB, and SGA. Overall, the ASR for LBW and PTB rose slightly (+ 6.2‰ and + 6.1‰, respectively), while the ASR for SGA declined moderately (-11.0‰), as shown in Fig. 1.

Specific trends for ABOs

To examine how the incidence rates of LBW differed by age and cohort, specific rates were plotted in Fig. 2. Age-specific incidence rates initially fell before age 25 years, then rose, resembling a “U-shaped” curve. Cohort-specific rates declined with the birth cohort, increased thereafter in the 15–24 years and 40–44 years age groups, and showed a steady upward trend in the 25–39 years age groups.

Figure 3 shows the trends of PTB in different age, period, and cohort groups. Age-specific incidence rates displayed the same “U-shaped” variation in PTB, whereas cohort-specific rates increased steadily in all age groups, except the 15–19 years age group.

The incidence rates of SGA according to age, period, and cohort are shown in Fig. 4. Overall, age-specific rates initially exhibited a decrease from age 15 to 35 years and then rose slightly after age 35 years. Rates among women aged 25–34 years remained stable over the entire period. However, for women in the younger or older age groups, the later the maternal birth cohort, the lower the incidence rate of SGA.

APC effects for ABOs

Figure 5 shows the estimated age, period, and birth cohort effects. Maternal age effect showed a changing trend in the incidence rate, while cohort and period effects were illustrated by risk ratios (RR). Variation trend in the three effects indicates that age and birth cohort were the main risk factors for ABOs, whereas the period was relatively less impactful. The APC effects were similar among LBW and PTB births but different from those in SGA infants. The effect of age on the trends in LBW and PTB displayed a “U-shaped” curve, reaching its lowest value in the mid-20s age group. The effect of birth cohort on LBW and PTB increased steadily before 1985 and then remained stable or declined slightly. When compared with the mothers born in 1985, those born in 1960 had the lowest RRs of 0.71 (95% confidence interval [CI], 0.65–0.78) for LBW, and 0.69 (95% CI, 0.64–0.75) for PTB. In contrast, a dramatic reduction in risk was observed in age and cohort effects in SGA infants. The RRs of SGA decreased from 1.82 (95% CI, 1.72–1.93) to 0.57 (95% CI, 0.54–0.61) during the 40 years' cohort, compared with the reference cohort of 1985. The RR of period effect in all three ABOs was approximately 1, without any obvious trend. The stratified APC effects by maternal education level and parity showed that the complex effects on SGA were modified by maternal education level and parity (Additional file ).

The age-period-cohort effects on the incidence rates of LBW, PTB, and SGA were evaluated using APC Poisson regression model. Comparisons of APC sub-models suggested that the full APC models were optimum, and incidence rates were significantly influenced by age and cohort effects when examining changes in residual deviance (Table 2). Age, period, and cohort effects, and their corresponding 95% CIs are described in Table 3.

Discussion

We examined the independent effects of maternal age, delivery period, and maternal birth cohort on the trends in LBW, PTB, and SGA births in Shanghai. The “U-shaped” relationship between maternal age and LBW/PTB was examined in this study. Mothers born before the 1980s had a lower incidence of PTB than those born recently. Meanwhile, the risk of SGA declined with advancing age and in cohorts since 1960. However, there were no obvious fluctuant trends in the three birth outcomes by period, suggesting that the observed temporal changes were mostly influenced by the maternal birth cohort.

Our findings on the association between maternal age, birth cohort, and LBW/PTB are consistent with those of previous studies [18, 19]. Extremes of maternal age increased the incidence of LBW/PTB, suggesting that natural ageing or social environments, or an interaction of both, should account for the association. Generally, older women are believed to have more obstetric complications, which in turn is a high-risk factor for ABOs. Young mothers, whose reproductive system is not biologically developed, are more likely to have a lower degree of education and socioeconomic strata [20].

We noted that the maternal birth cohort remarkably affected LBW/PTB. This pattern reflects that unique individual characteristics, including maternal nutrition and socioeconomic status prior to pregnancy, could profoundly influence pregnancy outcomes [21]. One potential explanation is that social and economic changes, such as experiencing remarkable lifestyle changes, increasing environmental pollution, and higher stress, may affect the female reproductive system [22, 23]. Maternal smoking, secondhand smoke exposure, drinking, and sedentary behaviour are the main unhealthy lifestyle factors leading to a higher prevalence of ABOs [24, 25]. An epidemiological study has also found that exposure to traffic-derived pollutants increases the risk of LBW, PTB, and growth retardation [26].

Interestingly, younger maternal age was associated with SGA in this study, while some studies have elucidated an opposite association [27–31]. The debatable association could be attributed to several factors: (1) various fetal growth curves or birth weight percentiles used to define SGA [32]; (2) ethnic or genetic differences across populations [33, 34]; and (3) the possibility of some small fetuses to achieve their normal growth potential. Although it is difficult to explain the decreased trend of SGA, we hypothesised that mothers could have benefited from accessible prenatal interventions and nutritional improvements. Due to rapid urbanisation since the 1980s, the nutritional and health status of Shanghai residents has greatly improved, and more fertility policies have been promoted [9], meaning that women born in more recent cohorts were unlikely to have SGA births. However, the opposite influence was found for mothers with higher education levels and primiparous mothers.

To the best of our knowledge, only a few studies have identified maternal APC effect on PTB/SGA [18, 30]. Although our study aimed to analyse the temporal influence of LBW, PTB, and SGA births, several important limitations should be considered. First, other determinants of ABOs, including maternal smoking, gestational weight gain, pregnancy complications, and paternal factors, were not collected in the database, which could illuminate the internal mechanisms of maternal age and cohort effects on ABOs [24, 35]. Second, the estimated gestational age, based on the first date of a woman's last menstrual period and not on ultrasound-based methods, may not accurately classify PTB/SGA infants. Although misclassification might influence the results mentioned above, it is unlikely to contribute to the temporal trends entirely. Third, the data was collected from a single birth registry database, which does not represent the nationwide population. However, Shanghai is a megacity with a large population (almost 25 million), which could be representative of the other developed cities in China and some Asian developed countries.

Our study suggests independent effects of maternal age, delivery period, and maternal birth cohort on trends in ABOs. Within the context of the universal 2-child policy, more women of advanced age prefer to raise a second child in China [36]. Although older women obtained better education and higher socioeconomic strata through social selection, they were more likely to suffer from obstetric complications. Both young and advanced mothers are more likely to have LBW/PTB; accordingly, more prenatal care and public education should be provided to younger and older pregnant women.

Conclusions

In summary, we found strong maternal age and birth cohort effects on the three birth outcomes, suggesting that younger and older pregnant women should be key target population groups for perinatal care and treatment. Moreover, there was a continuous increase in the incidence rates of LBW and PTB, inspiring the need to formulate public health intervention and prevention policies in the developed areas of China. Among women in the same age groups, those born in more recent eras had a lower risk of SGA. More knowledge of how these trends are associated with ABOs in China is required.

Abbreviations

ABOs, adverse birth outcomes; LBW, low birth weight; PTB, preterm birth; SGA, small for gestational age; SCDC, Shanghai Municipal Centre for Disease Control and Prevention; APC, age-period-cohort; CI, confidence interval; RR, risk ratio; SDs, standard deviations

Declarations

Ethics approval

This study was a retrospective, population-based cohort study approved by the Ethics Review Committee of the Shanghai Municipal Centre for Disease Control and Prevention (SCDC), and all methods were carried out following relevant guidelines and regulations. As only de-identified routinely collected surveillance data were used, the requirement to obtain informed consent was waived.

Name of the ethics committee: Shanghai Municipal Centre for Disease Control and Prevention Ethics Review Committee

The relevant legislation: Informed consent may be waived if information and/or biological specimens obtained from health surveillance are reused without further tracking of subject information.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and analysed in the study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was funded by National Natural Science Foundation of China (82003486). The funding sources had no influence on the content of and no role in the writing of this work.

Authors' contributions

Study concept and design: R.Z. and H.Y.; Methodology: H.Y. and R.Z.; Formal Analysis: R.Z. and H.Y.; Data Curation: H.Y., R.C. and S.J.; Writing—Original Draft: H.Y.; Writing—Review & Editing: H.Y., R.Z., N.Q. and L.C.; Project administration: C.W. and F.W.; Funding acquisition: H.Y. and C.W.; Critical revision of the manuscript for important intellectual content: All authors.

Acknowledgements

The authors are grateful to all those who contributed to project implementation, including researchers, project coordinators, data collectors, and data clerks.

The authors would like to thank Editage (www.editage.cn) for English language editing.

Authors' information

Rongfei Zhou, [email protected]

Huiting Yu, [email protected]

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