The Impact of Multiple Births on Fertility: Stopping and Spacing in the United States During the Demographic Transition.

Multiple births strain mothers' and families' resources in ways that should highlight preferences for family size, birth spacing, and parity-dependent stopping behavior. Couples with surviving twins reach their target family size sooner than other couples and should be more likely to practice family limitation. Twins are also a greater burden on the mother's time and health, which could lead to postponing the next birth, even among couples who want additional children. We examine these hypotheses by analyzing families with twins in the 1900 and 1910 U.S. Censuses. Using reconstructed birth histories for more than 7 million women in the IPUMS full-count 1900 and 1910 datasets and event-history methods (Kaplan-Meier curves, cure models), we find clear evidence of family limitation following a multiple birth. Couples who had twins or triplets were more likely to stop childbearing, and those who continued having children delayed their next birth. Responses to multiple births were larger in groups previously identified as leaders in the transition to smaller families, and roughly one third of couples stopped after one or two children. We find no evidence that some groups relied primarily on birth spacing to reduce family size while others relied primarily on stopping.

Genetic regulation of ovulation rate and multiple births.

Ovulation rate in many mammalian species is controlled to regulate the numbers of offspring and maximise reproductive success. Pathways that regulate ovulation rate still respond to genetic and environmental factors and show considerable variation within and between species. Genetic segregation, positional cloning, and association studies have discovered numerous mutations and genetic risk factors that contribute to this variation. Notable among the discoveries has been the role of mutations in bone morphogenetic protein 15 (BMP15 ), growth differentiation factor 9 (GDF9 ) and bone morphogenetic protein receptor type 1B (BMPR1B ) from the intra-ovarian signalling pathway contributing to the evidence that signalling from the oocyte is the key driver in follicle regulation rather than circulating gonadotrophin concentrations. Multiple variants in different domains of BMP15 and GDF9 result in partial or complete loss of function of the proteins providing insights into their functional roles and differential regulation contributing to species differences in ovulation rate. Early success encouraged many more studies in prolific strains of sheep, cattle and goats providing a valuable catalogue of genetic variants of large effect increasing ovulation rate and litter size. More recently, genetic association studies are beginning to identify genetic risk factors with smaller effects. Most genes implicated are from pathways with defined roles in regulation of the ovarian function. However, some genomic regions suggest regulation by novel genes. Continuing genetic and related functional studies will add further to our understanding of the detailed regulation of ovulation rate and litter size with implications for health and animal production systems.

Multiple births from medically assisted reproduction: contribution of different types of procedures and trends over time.

OBJECTIVE: To evaluate the relative impact of different strategies of medically assisted reproduction (MAR), i.e. first line treatment (ovarian stimulation with or without intrauterine insemination) and in vitro fertilization (IVF) procedures (conventional IVF or intracytoplasmic sperm injection), on the risk of multiple births. STUDY DESIGN: We utilized the health care utilization databases of the Lombardy region to identify births resulting from MAR between 2007 and 2022. We gathered data on the total number of multiple births and calculated the prevalence rate by dividing the number of multiples by the total number of births. To examine the temporal trend in the proportion of multiple births after MAR over time, a linear regression model was employed separately for different types of techniques and in strata of maternal age. RESULTS: A total of 30,900 births after MAR were included; 4485 (14.5 %) first line treatments and 26,415 (85.5 %) IVF techniques. Overall, 4823 (15.6 %) multiple births were identified. The frequency of multiple births over the study period decreased from 22.0 % in 2007 to 8.7 % in 2022 (p < 0.01). Multiple births from first line treatments were stable ranging from 13.5 % in 2007-2008 to 12.0 % in 2021-2022 (p = 0.29). Multiple births from IVF procedures decreased from 23.8 % in 2007-2008 to 8.4 % in 2021-2022 (p < 0.01). Stratifying for maternal age (i.e. < 35 and ≥ 35 years), the trends remained consistent. CONCLUSIONS: The reduction in multiple births has been influenced by changes in IVF strategy and procedures. The decline has been gradual but steady since 2009, when a law restricting embryo freezing was repealed in Italy. In contrast, the proportion of multiple births resulting from first line treatments has remained constant over time. Despite declining, multiple births from MAR remained about one order of magnitude higher than those from spontaneous pregnancies.

Assisted Reproductive Technology, Multiple Births, and Perinatal Outcomes in Taiwan from 2001 to 2020.

OBJECTIVE: To investigate the effect of the Assisted Reproduction Act, implemented in 2007 in Taiwan to reduce the number of embryos to transfer, on the trends over time regarding the rate of multiple births, preterm delivery, low birth weight (LBW), and small for gestational age (SGA) among deliveries using assisted reproductive technology (ART). STUDY DESIGN: From the Birth Reporting Registry and the Assisted Reproduction Registry, we retrieved data of 4 016 530 live birth deliveries between 2001 and 2020; among them 71 000 (1.77%) were after ART. We calculated the rate of multiples and perinatal outcomes per 1000 deliveries annually from 2001 to 2020 for deliveries using and not using ART and computed the population attributable risk. We performed interrupted time series to assess the effect of the intervention, ie, the Assisted Reproduction Act. RESULTS: The proportion of deliveries following ART was 0.57% in 2001 and increased to 4.03% in 2020. After the intervention, there were decreasing trends over time for rates of multiples (-10.63 per year, P < .001), preterm delivery (-6.74, P = .003), LBW (-9.38, P < .001), and SGA (-4.48, P = .001) among ART deliveries. There was also an immediate decrease right after intervention (-53.45, P = .005) for SGA after ART. The population attributable risk trends before and after intervention were both increasing for all outcomes. CONCLUSIONS: The Assisted Reproduction Act in Taiwan was associated with a decreasing trend of multiples, preterm delivery, LBW, and SGA over time since 2008 among ART deliveries. In particular, there was an immediate decrease of SGA right after the intervention.

The role of multiple birth and birth complications in the association between assisted reproductive technology conception and autism diagnosis.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

The impact of China's universal two-child policy on total, preterm, and multiple births: a nationwide interrupted time-series analysis.

BACKGROUND: Although years have passed since the implementation of China's universal two-child policy, the effectiveness of this policy remains unclear. To address this knowledge gap, we, here, assessed the impact of the two-child policy on total live births, preterm births, and multiple live births. METHODS: Data identifying pregnancies resulting in at least one live birth between April 1 2013 and December 31 2018 were collected from the Hospital Quality Monitoring System database. Using an interrupted time-series analysis, we estimated immediate level changes and long-term trends in total, preterm (birth before 37 weeks' gestation), and multiple live births that had occurred after July 2016, when the universal two-child policy had taken effect. RESULTS: A total of 8,273,622 live births were reported during the study time frame. The number of live births (p = 0.277), preterm births (p = 0.052), and multiple births (p = 0.856) per month slightly increased immediately after July 2016, but these increases did not meet statistical significance. Further, all three outcomes showed a significant downward trend that lasted until the end of 2018 (p < 0.0001 for all). Among all live births, the percentage of preterm births remained stable (p = 0.101), while the percentage of multiple live births that were preterm significantly increased (trend change = 0.21% per month, 95% CI 0.14 to 0.28, p < 0.0001). The percentage of live multiple births among all live births significantly decreased (p for trend = 0.0039). CONCLUSIONS: Overall, our data reveal a transient baby boom, as well as an increase in the proportion of live multiple births that were preterm, after China's two-child policy took effect. The latter should be noted by healthcare professionals due to the high risk of complications and special medical care required by preterm babies.

The needs of multiple birth families during the first 1001 critical days: A rapid review with a systematic literature search and narrative synthesis.

OBJECTIVE: Supporting families during the first 1001 days from conception to the age of two is vital for setting the emotional, cognitive, and physical building blocks for children's futures. Families with twins, triplets, or higher order multiples (multiple birth families) have unique challenges due to caring for more than one baby at the same time. Therefore, identifying the needs of multiple birth families is necessary to provide optimum support during the first 1001 critical days. DESIGN: A rapid review was undertaken to synthesize knowledge of the needs of multiple birth families in the United Kingdom (UK) during the first 1001 critical days. Findings from five databases (MEDLINE, APA PsycArticles, APA PsycInfo, CINAHL, and Web of Science) for peer-reviewed studies and grey literature published between 2012 and 2022 were synthesized. Fifteen studies were reviewed using narrative synthesis. RESULTS: Multiple birth families have unique and complex emotional and practical needs across the first 1001 critical days, and in particular, the first-year post birth, impacted further by complicated pregnancies and prematurity. Needs were identified within the four key themes: high risk pregnancy and birth; transformed reality of raising multiples; inadequate support; and positively affecting experiences. Health professional support was inconsistent and particularly lacking in intrapartum, postnatal, and community care including transition. CONCLUSION: Multiple birth families' needs should be considered in the design and delivery of care within the first 1001 critical days, especially within the first year after birth. Multiples specific advice across the first 1001 critical days is needed and training for health professionals to adapt universal advice for this population is one way to achieve this. Further research is needed to ensure this advice is evidence based and effective.

The Genetic Determinants of Axial Length: From Microphthalmia to High Myopia in Childhood.

The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is 23.5 mm, but the molecular mechanisms regulating ocular axial length remain poorly understood. Underdevelopment can lead to microphthalmia (defined as a small eye with an axial length of less than 19 mm at 1 year of age or less than 21 mm in adulthood) within the first trimester of pregnancy. However, continued overgrowth can lead to axial high myopia (an enlarged eye with an axial length of 26.5 mm or more) at any age. Both conditions show high genetic and phenotypic heterogeneity associated with significant visual morbidity worldwide. More than 90 genes can contribute to microphthalmia, and several hundred genes are associated with myopia, yet diagnostic yields are low. Crucially, the genetic pathways underpinning the specification of eye size are only now being discovered, with evidence suggesting that shared molecular pathways regulate under- or overgrowth of the eye. Improving our mechanistic understanding of axial length determination will help better inform us of genotype-phenotype correlations in both microphthalmia and myopia, dissect gene-environment interactions in myopia, and develop postnatal therapies that may influence overall eye growth.

Associations between neighborhood greenspace and multiple birth outcomes across two metropolitan areas in Australia.

BACKGROUND: Beneficial effects of greenspace on birth outcomes have been reported. However, insights on key windows of exposure and underlying mechanisms are needed. METHOD: Births in Sydney (2016-2019) were retrieved from NSW Midwives Data Collection. Births in Brisbane (2000-2014) were retrieved from Queensland Health Perinatal Data Collection. Satellite image-derived normalized difference vegetation index (NDVI) and night time light (NTL) index were used. For each city, linear regression models were used to assess associations between greenspace and birth weight, and logistic models to estimate the risks of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) per 0.1 increase in NDVI. We examined the trimester-specific associations, and heterogeneities by night time light. RESULTS: The study included 193,264 singleton births in Sydney and 155,606 singleton births in Brisbane. An 0.1 increase in greenspace during whole pregnancy was associated with 17.4 g (95%CI: 14.5 to 20.2) increase in birth weight in Sydney, and 15.1 g (95%CI: 12.0 to 18.5) in Brisbane. The odds ratios were 0.98 (95%CI: 0.97 to 0.99) for LBW, 0.99 (95%CI: 0.98 to 1.00) for PTB, and 0.98 (95%CI: 0.96 to 0.99) for SGA per 0.1 increase in NDVI during whole pregnancy for participants in Sydney. Similarly, reduced odds of adverse birth outcomes were observed in Brisbane. Trimester specific models demonstrated a consistent pattern of associations in the same direction across all outcomes. We found that effects of greenspace exposure on birth outcomes attenuated after adjusting for NTL, but stronger effects among babies of mothers from areas with more NTL. CONCLUSIONS AND RELEVANCE: These findings suggest a beneficial association between neighborhood greenspace and healthier pregnancies in urban areas. We provide novel evidence of interactions between greenspace and NTL.

Differences in prenatal diagnosis rate of congenital anomalies associated with singletons and multiple births: An observational study of more than 1.9 million births in Zhejiang Province, eastern China, during 2012-2018.

OBJECTIVE: To characterize differences in the prenatal detection of congenital anomalies (CAs) associated with singleton and multiple births. METHODS: This observational study covered all births registered in the CA surveillance system in Zhejiang Province of China during 2012-2018. Differences in the incidence and characteristics between singletons and multiple births with CAs were tested. Multivariate logistic regression models were performed to explore the associations of prenatal detection rate of CAs with multiple births. RESULTS: Totals of 49 872 singletons and 3324 multiple births with CAs were analyzed. The mean incidences of CA for single and multiple births were 27.12 and 54.42 per 1000 births, respectively. After adjustment for covariates, CAs associated with multiple births were less likely to be diagnosed prenatally (adjusted odds ratio [OR] 0.38, 95% confidence interval [CI] 0.34-0.43), as were congenital heart defects, congenital hydrocephalus, cleft lip with cleft palate, cleft lip without cleft palate, limb reduction defects, congenital diaphragmatic hernia, trisomy 21 syndrome, congenital malformation of the urinary system, and other chromosomal malformation, compared with singletons with CAs. CONCLUSION: Multiple birth is associated with a significantly higher risk of CA, but a significantly lower prenatal diagnosis rate. Therefore, the healthcare of women with multiple pregnancy and their fetuses should be strengthened.

Self-cleaving peptides for expression of multiple genes in Dictyostelium discoideum.

The social amoeba Dictyostelium discoideum is a model for a wide range of biological processes including chemotaxis, cell-cell communication, phagocytosis, and development. Interrogating these processes with modern genetic tools often requires the expression of multiple transgenes. While it is possible to transfect multiple transcriptional units, the use of separate promoters and terminators for each gene leads to large plasmid sizes and possible interference between units. In many eukaryotic systems this challenge has been addressed through polycistronic expression mediated by 2A viral peptides, permitting efficient, co-regulated gene expression. Here, we screen the most commonly used 2A peptides, porcine teschovirus-1 2A (P2A), Thosea asigna virus 2A (T2A), equine rhinitis A virus 2A (E2A), and foot-and-mouth disease virus 2A (F2A), for activity in D. discoideum and find that all the screened 2A sequences are effective. However, combining the coding sequences of two proteins into a single transcript leads to notable strain-dependent decreases in expression level, suggesting additional factors regulate gene expression in D. discoideum that merit further investigation. Our results show that P2A is the optimal sequence for polycistronic expression in D. discoideum, opening up new possibilities for genetic engineering in this model system.

Trends and characteristics of multiple births in Baoan Shenzhen: A retrospective study over a decade.

Background: Shenzhen has the largest and youngest foreign population among all cities in China. The reproductive health of pregnant women from different backgrounds is a social issue that deserves attention. In the past decade, China has liberalized its population policies to stimulate population growth, and the proportion of multiple births has continued to increase. Method: This retrospective cohort included 526,654 newborns born in Baoan, Shenzhen, from January 1, 2009, to December 31, 2019, including 515,016 singletons and 11,638 twins or triplets. Univariate regression models were used to analyze the effects of maternal sociodemographic characteristics, physiological characteristics, medical history, antenatal care and other factors associated with single vs. multiple births and to elucidate the changing trends of different factors affecting multiple births in the past 11 years. Additionally, fetal development in multiple births was analyzed by generalized linear mixed models. Results: The rates of pregnancy complications, preterm birth, and advanced-age pregnancy were significantly higher in the multiple birth mothers than in single birth mothers, and more multiple pregnancies were achieved through assisted reproductive technologies. The rates of adverse outcomes such as stillbirth, malformation, hypoxia, and ultralow body weight in multiple fetuses were significantly higher than that in singleton fetuses. The trend analysis from 2009 to 2019 showed that the socioeconomic status and health level of mothers with multiple births improved over time, and the risk during pregnancy generally decreased. Simultaneously, the development indicators of multiple fetuses have improved year by year, and the proportion of adverse outcomes has also decreased significantly. A low pre-natal care utilization rate was shown to be detrimental to the development of multiple fetuses. Independent risk factors for hypoxia and very low birth weight were also identified. The differences in secular trends between two birth groups were further revealed by time series models. Conclusion: This study presented a comprehensive survey of multiple pregnancies in the area with the largest population inflow in China. This study identified the factors that affect the health of multiple birth mothers and their fetuses, particularly suggesting that preterm birth rates and the use of assisted reproduction remain high. The findings provide a basis for the formulation of individualized pre-natal care, assisted reproductive guidance and healthcare policies for multiple births.

Under age five children survival times in Nigeria: a Bayesian spatial modeling approach.

BACKGROUND: Nigeria is among the top five countries in the world with the highest under-five mortality rates. In addition to the general leading causes of under-five mortality, studies have shown that disparity in sociocultural values and practices across ethnic groups in Nigeria influence child survival, thus there is a need for scientific validation. This study quantified the survival probabilities and the impact of socioeconomic and demographic factors, proximate and biological determinants, and environmental factors on the risk of under-five mortality in Nigeria. METHODS: The Kaplan-Meier survival curve, Nelson Aalen hazard curve, and components survival probabilities were estimated. The Exponential, Gamma, Log-normal, Weibull, and Cox hazard models in a Bayesian mixed effect hierarchical hazard modeling framework with spatial components were considered, and the Deviance and Watanabe Akaike information criteria were used to select the best model for inference. A [Formula: see text] level of significance was assumed throughout this work. The 2018 Nigeria Demographic and Health Survey dataset was used, and the outcome variable was the time between birth and death or birth and the date of interview for children who were alive on the day of the interview. RESULTS: Findings show that the probability of a child dying within the first two months is 0.04, and the probability of a boy child dying before attaining age five is 0.106, while a girl child is 0.094 probability. Gender, maternal education, household wealth status, source of water and toilet facility, residence, mass media, frequency of antenatal and postnatal visits, marital status, place of delivery, multiple births, who decide healthcare use, use of bednet are significant risk factors of child mortality in Nigeria. The mortality risk is high among the maternal age group below 24 and above 44years, and birth weight below 2.5Kg and above 4.5Kg. The under-five mortality risk is severe in Kebbi, Kaduna, Jigawa, Adamawa, Gombe, Kano, Kogi, Nasarawa, Plateau, and Sokoto states in Nigeria. CONCLUSION: This study accentuates the need for special attention for the first two months after childbirth as it is the age group with the highest expected mortality. A practicable way to minimize death in the early life of children is to improve maternal healthcare service, promote maternal education, encourage delivery in healthcare facilities, positive parental attitude to support multiple births, poverty alleviation programs for the less privileged, and a prioritized intervention to Northern Nigeria.

Effects of assisted reproductive technology on severe maternal morbidity risk in both singleton and multiple births in Korea: A nationwide population-based cohort study.

BACKGROUND: Whether infertility treatment predicts severe maternal morbidity in both singleton and twin pregnancies is controversial. We conducted this nationwide population-based cohort study to compare pregnancies conceived through assisted reproductive technology treatments, such as intrauterine insemination or in vitro fertilization, with unassisted pregnancies. METHODS: This study included 269,930 women who experienced childbirth in 2018, using data of the National Health Insurance Service National Delivery Cohort in Korea. The primary outcome was assessed using a severe maternal morbidity algorithm developed by the Centers for Disease Control and Prevention in the United States. A modified Poisson regression was used to estimate the adjusted risk ratio of severe maternal morbidity. RESULTS: Severe maternal morbidity occurred in 6,333 (2.3%) of 280,612 deliveries investigated. The risk of severe maternal morbidity was approximately 1.5-fold higher among women who received in vitro fertilization (risk ratio: 1.51, 95% confidence interval: 1.36-1.68) than among fertile women. However, no significant association between intrauterine insemination and maternal morbidity was identified. Via subgroup analysis, in vitro fertilization increased the risk of severe maternal morbidity by 1.6- and 1.3-fold in singleton and multiple births, respectively (singleton: risk ratio: 1.62, 95% confidence interval: 1.43-1.83; multiple birth: risk ratio: 1.31, 95% confidence interval: 1.07-1.60). CONCLUSIONS: This study suggested that in vitro fertilization was associated with the risk of severe maternal morbidity in both singleton and multiple births. Further research should identify patient- and treatment-specific factors that may mitigate or prevent adverse maternal health risks.

Associated regions for multiple birth in Brown Swiss and Original Braunvieh cattle on chromosomes 15 and 11.

Twin and multiple births have negative effects on the performance and health of cows and calves. To decipher the genetic architecture of this trait in the two Swiss Brown Swiss cattle populations, we performed various association analyses based on de-regressed breeding values. Genome-wide association analyses were executed using ~600 K imputed SNPs for the maternal multiple birth trait in ~3500 Original Braunvieh and ~7800 Brown Swiss animals. Significantly associated QTL were observed on different chromosomes for both breeds. We have identified on chromosome 11 a QTL that explains ~6% of the total genetic variance of the maternal multiple birth trait in Original Braunvieh. For the Brown Swiss breed, we have discovered a QTL on chromosome 15 that accounts for ~4% of the total genetic variance. For Original Braunvieh, subsequent haplotype analysis revealed a 90-kb window on chromosome 11 at 88 Mb, where a likely regulatory region is located close to the ID2 gene. In Brown Swiss, a 130-kb window at 75 Mb on chromosome 15 was identified. Analysis of whole-genome sequence data using linkage-disequilibrium estimation revealed possible causal variants for the identified QTL. A presumably regulatory variant in the non-coding 5' region of the ID2 gene was strongly associated with the haplotype for Original Braunvieh. In Brown Swiss, an intron variant in PRDM11, one 3' UTR variant in SYT13 and three intergenic variants 5' upstream of SYT13 were identified as candidate variants for the trait multiple birth maternal. In this study, we report for the first time QTL for the trait of multiple births in Original Braunvieh and Brown Swiss cattle. Moreover, our findings are another step towards a better understanding of the complex genetic architecture of this polygenic trait.

Examination of multiple birth as a predictor of autism symptom severity and developmental functioning in an early intervention sample.

Multiple birth is one of several perinatal factors associated with increased risk for autism spectrum disorder (ASD); however, complexity in its relationship to ASD symptoms and developmental functioning remains. The present study investigated perinatal risk factors for ASD, primarily focusing on birth status, within a large early intervention sample. In particular, the relationship between ASD, perinatal factors, and the effect of birth status on developmental functioning and ASD symptom severity were examined in youth with and without ASD classification who were born singly or were the product of a multiple birth. Overall, the presence of other perinatal risk factors, including prematurity, low birth weight, and advanced parental age, was primarily related to birth status and not to ASD classification, while severity of ASD symptoms and developmental impairments were primarily related to ASD classification and not to birth status. Study findings and implications for early screening of children with developmental delays are discussed.

Supporting multiple birth families: Perceptions and experiences of health visitors.

OBJECTIVE: To explore the current practice and perceptions of health visitors in supporting multiple birth families. DESIGN AND SAMPLE: Practicing health visitors across the United Kingdom were invited to complete a cross-sectional, descriptive, online survey. The questionnaire covered multiple birth caseload, education received about multiples and the experience of working with families. Two-hundred and ninety health visitors completed the questionnaire. Descriptive and inferential statistics were used for analysis of the quantitative components and thematic analysis for the qualitative data. RESULTS: Most health visitors had twins on their current workload. Most health visitors had not received any specific training or continuing professional development regarding the needs of multiple birth families. Supporting the families within the confines of reduced time and increased workload was challenging. Daily tasks of caring for multiples were the main areas that health visitors and parents wanted more information about. CONCLUSIONS: In the United Kingdom, health visitors are uniquely positioned to support multiple birth families, in particular during the more challenging early years. However, the findings of this study suggest that many health visitors are aware that the care and support that they are able to provide multiple birth families falls short of meeting their needs.

Multiple births and low birth weight: Evidence from South Korea.

OBJECTIVE: The proportion of multiple births has risen rapidly worldwide. Multiple births are likely to affect birth weight, which results in low birth weight (LBW) of less than 2500 g, possibly, because multiples are more likely to be born prematurely or less than 37 weeks into pregnancy. Using data from South Korea, this study aims to estimate the contribution of the rise in multiples to the rise in LBW incidence. METHODS: Based on data from 2000 to 2017, we estimated the effect of multiples on LBW rates using linear regression analysis. Based on the regression analysis and the change in the proportion of multiples during this period, we calculated the contribution of the rise in multiples to the rise in LBW incidence using the total differential. In other words, we divided the change in LBW during the period due to the change in multiples by the total change during the period. The data are from the birth registry of the National Statistical Office, which contains information on the 8.4 million live births during the period 2000-2017. RESULTS: We found that a 1 percentage point increase in multiples increases the proportion of LBWs by 0.495 percentage points. In addition, because the changes in the proportion of multiples and LBWs from 2000 to 2017 are 2.2 and 2.4 percentage points, respectively, 1.1 percentage points or 45.8% of the increase in LBWs over the period is due to the increase in multiples. CONCLUSION: Since the Korean government introduced a measure to reduce the number of transferred embryos recently, one may expect that multiples in Korea would reduce in the near future, as it did in other countries. Subsequently, the incidence of LBW children is also likely to reduce, which is desirable in terms of the children's health outcomes.