Objective The aim of this study was to examine this association between maternal weight during pregnancy and the incidence of hospitalisations for infectious diseases during early childhood.
Design A population-based cohort study.
Setting A national cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register and the Longitudinal integration database for health insurance and labour market studies.
Patients 693 007 children born in Sweden between 1998 and 2006.
Main outcome measures Number of hospitalisations for infectious diseases during the first 5 years of life, overall and for categories of infectious diseases (lower respiratory, enteric, upper respiratory, genitourinary, perinatal, skin and soft tissue, neurological and eye, digestive tract, bloodstream and other infections).
Results Overweight (body mass index (BMI) 25.0–29.9) and obesity (BMI≥30) during pregnancy were associated with a higher overall incidence of hospitalisations for infectious diseases, adjusted incidence rate ratio (IRR) 1.05 (95% CI 1.03 to 1.06) and adjusted IRR 1.18 (95% CI 1.16 to 1.21). Overweight and obesity during pregnancy were strongly associated with perinatal infections, adjusted IRR 1.34 (95% CI 1.25 to 1.44) and adjusted IRR 1.72 (95% CI 1.57 to 1.88). In contrast, we found no association between maternal weight during pregnancy and infections of skin and soft tissue, the nervous system, the digestive tract or the bloodstream.
Conclusions We observed an association between overweight and obesity during pregnancy, and hospitalisations for infectious diseases during early childhood.
- infectious diseases
- public health
- community child health
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What is already known on this topic?
Children of overweight mothers are more likely to have birth complications, congenital anomalies and other detrimental conditions.
An increased risk of infectious disease in children of overweight mothers has been observed in some smaller cohort studies.
There is no previous large population-based cohort study on the association between overweight during pregnancy and the risk of infectious disease during early childhood.
What this study adds?
We found an association between overweight and obesity during pregnancy and the overall risk of infectious disease hospitalisations during early childhood.
Overweight and obesity during pregnancy were both strongly associated with perinatal infections; obesity during pregnancy was also modestly associated with respiratory and genitourinary infections.
Excess weight during pregnancy is a global health issue. Overweight (body mass index (BMI) 25.0–29.9) and obesity (BMI≥30.0) are increasing among women of reproductive age (20–49 years) in all regions of the world.1 Furthermore, increasing levels of excess weight during pregnancy have been reported from many countries including UK, Tanzania and Sweden.2–4 In Sweden, the prevalence of overweight during pregnancy increased from around 9% in 1978 to 25.4% in 2015, whereas the prevalence obesity increased from around 2% to 13.6%.5 6
Excess weight during pregnancy is associated with severe consequences for the mother, fetus and child. Obesity during pregnancy increases the risk of for example, pre-eclampsia, gestational diabetes, infections and pulmonary embolism.7–10 Moreover, obesity during pregnancy is associated with increased risks for preterm birth, stillbirth and congenital malformations of the nervous system and heart.10 After birth, children of obese mothers have increased risk of asphyxia (low APGAR-score) and death during the neonatal period.4 7
While it is well established that excess weight during pregnancy is associated with many adverse outcomes, less is known about its association with infectious diseases during early childhood. Previous studies have shown that maternal obesity before the pregnancy is associated with an increased risk for pneumonia during the first 6 months after birth and hospitalisations for infectious diseases during the first 5 years of life.11 12 Nevertheless, there is still a scarcity of studies assessing the association between maternal weight before or during pregnancy and infectious diseases in early childhood. Additionally, no previous study systematically examined the associations for different categories of infectious diseases. Therefore, the aim of this study was to examine the association between excess weight during pregnancy and infectious disease incidence, which, in this study is measured by number of hospitalisations for infectious diseases during the first 5 years of life.
Sweden is a welfare state with a publicly funded healthcare system, free education and a comprehensive social insurance system. Healthcare during childhood and adolescence is provided for free. All children are also offered a standard vaccination programme.13 The social insurance system includes social assistance, which is an income allowance from social authorities that provides a minimum living standard including housing, food, clothes and health.14
Study population and data retrieval
This is a population-based cohort study of children born in Sweden between 1998 and 2006. The cohort was created by combining several registers held by the National Board of Health and Welfare and by Statistics Sweden. The Medical Birth Register (MBR) contains information on prenatal, delivery and neonatal care (up to 28 days). It covers 98%–99% of all births in Sweden.15 The Cause of Death Register contains information on deaths including a Statistical Classification of Diseases (ICD) code of underlying cause and covers over 97% all deaths.16 LISA (Longitudinal integration database for health insurance and labour market studies) contains socioeconomic data including education level. The Swedish Total Population Register contains information about migration. The National Inpatient Register contains information about hospital admissions including ICD code for primary diagnosis and cover over 99% of all inpatient hospital admissions in Sweden.17 These registers were linked together using the national registration number, a unique personal identification number assigned to all Swedish residents at birth or immigration. The data were linked and anonymised by the Centre for Epidemiology at the Swedish National Board of Health and Welfare. The final cohort included all live births recorded in the MBR during the study period.
Maternal BMI during pregnancy was calculated from height and weight recorded in MBR. Height was self-reported while weight was measured at the first antenatal care visit, which occurs between 8 and 12 weeks of gestation for approximately 90% of pregnant women.15 In comparison with pre-pregnancy weight, weight measured in the first trimester will be slightly higher.18 Maternal BMI during pregnancy was categorised, according to WHO guidelines for BMI, into underweight (<18.5), normal (18.5–24.9), overweight (25.0–29.9) and obese (≥30.0).19
Data on maternal age, maternal smoking, parity and geographic region was obtained from the MBR. Maternal smoking was reported during an interview at the first antenatal care visit, this self-reported data show high agreement with cotinine (a metabolite of nicotine) levels in maternal serum (95% of self-reported non-smokers have low levels of serum cotinine).20 Parity was recorded as the number of previous live or stillbirths+1. The region is the county where the mother resided at the time of delivery.
Socioeconomic status was measured by maternal education and data were obtained from LISA for the year of birth. Maternal education was divided into lower secondary school or less (9 years or less), upper secondary school (10–12 years), short postsecondary education (13–15 years) and long postsecondary education (16 years or more).
The main outcome was number of inpatient hospital admissions with a principal diagnosis of infectious disease recorded in NPR during the first 5 years of life. Hospital admissions were recorded using International Classification of Disease, Tenth Revision (ICD-10) codes and mapped onto a modified classification scheme that distinguishes between 10 major infectious disease categories (lower respiratory, enteric, upper respiratory, genitourinary, perinatal, skin and soft tissue, neurological and eye, digestive tract, bloodstream and other infections).21 Readmissions on the same day with the same infectious category were excluded. A list of ICD codes is included in online supplementary appendix A.
Supplementary file 1
Children were followed until 5 years of age or censoring due to death or international migration. Incidence rates (IRs) were estimated for overall risk of infectious diseases and for specific subsets of infectious diseases. The IRs were calculated as number of hospital admissions per 100 000 person-years (PY) at risk.
Crude and adjusted associations of the association between pregnancy weight categories (exposure) and number of hospitalisations (outcomes) were calculated using negative binomial regression models and presented as incidence rate ratios (IRR). The adjusted models were controlled for potentially confounding effects of maternal age, maternal education level, maternal smoking, parity, geographic region and time trends (year of birth). A separate model was fitted for each outcome (overall and categories of infectious diseases). All analyses were restricted to observations with complete information on all covariates. Negative binomial models were chosen over Poisson regression models, a choice that was informed by a likelihood ratio test for overdispersion.
In sensitivity analysis, we used multiple imputation methods to impute missing data.22 The missing data pattern was arbitrary, and we therefore used a chained equations approach. We developed two predictive models. Both models included all variables in the adjusted substantive model and the outcome (overall number of hospitalisations for infectious diseases). In the first predictive model, we first imputed region, then maternal education, maternal smoking and pregnancy BMI. In the second predictive model, we reversed the order of imputation. All missing values were imputed using ordinal logistic regression. Ten imputed datasets were generated for each predictive model.
All statistical analyses were performed using Stata V.14 (Stata, 2015. Stata Statistical Software: Release 14. College Station, Texas, USA).
The MBR contained 838 756 records of live births between 1998 and 2006. Children with missing data on pregnancy BMI (n=114 588) or covariates (n=31 161) were excluded from the complete case analyses. We followed all remaining 693 007 children (83% of the original cohort) until 5 years of age, censoring due to death (n=2001) or international migration (n=9338). The study included 3 432 561 PY of follow-up time. During the follow-up period, 125 297 inpatient hospital admissions for infectious diseases were recorded in NPR. Readmissions on the same day and recorded with the same infectious disease category were excluded (n=287) leaving 125 010 hospital admissions.
Table 1 shows key background characteristics for the study population. Women with low education level were, in comparison with women with and long postsecondary education, more likely to be overweight or obese during pregnancy. Smoking during pregnancy and parity ≥4 were also associated with obesity during pregnancy. In contrast, women who resided in Stockholm (the capital) region were less likely to be obese.
Table 2 shows incidence rates (IR) per 100 000 person-years (PY) overall and for categories of infectious diseases, by pregnancy BMI categories. Overall incidence of infectious disease hospitalisations increased considerably with pregnancy BMI, from 3479 per 100,000 PY (95% CI 3454 to 3504) for children of normal weight mothers to 3739 per 100 000 PY (95% CI 3698 to 3780) for children of overweight mothers and 4341 per 100 000 PY (95% CI 4274 to 4410) for children of obese mothers. The three most important categories of infectious diseases were lower respiratory, enteric and upper respiratory infections. The largest difference between pregnancy weight categories was observed for perinatal infections.
Figure 1 shows the association between the BMI during pregnancy and overall number of hospitalisations for infectious diseases during the first 5 years of life. The IR of hospital admissions for infectious diseases was 5% higher for children whose mothers were overweight during pregnancy (adjusted incidence rate ratio (IRR) 1.05, 95% CI 1.03 to 1.06). Children of obese mothers were 18% more likely to be admitted (adjusted IRR 1.18, 95% CI 1.16 to 1.21). Online supplementary appendix B includes full regression results for the analyses presented in figure 1 as well as results from models with multiple imputation for missing values. Results after multiple imputation were consistent with those from the complete case analyses.
Supplementary file 2
Figure 2 shows associations between BMI during pregnancy and the number of hospitalisations for specific infectious disease categories during the first 5 years of life. In the adjusted analysis, overweight and obesity during pregnancy were associated with upper respiratory infections, genitourinary infections, perinatal infections and other infections. In addition, obesity during pregnancy was also associated with lower respiratory and enteric infections. In contrast, overweight and obesity during pregnancy were not associated with skin and soft tissue infections, neurological and eye infections, digestive tract infections and bloodstream infections. The risk of perinatal infections was 34% higher among children whose mothers were overweight (adjusted IRR 1.34, 95% CI 1.25 to 1.44) and 72% higher among children to obese mothers (adjusted IRR 1.72, 95% CI 1.57 to 1.88). However, only 3.5% of the infectious disease-related admissions were due to perinatal infections. Online supplementary appendix C includes full regression results for the analyses presented in figure 2 as well as results from models with multiple imputation for missing values. Results after multiple imputation were largely consistent with those from the complete case analyses.
Supplementary file 3
We found a moderate association between obesity during pregnancy and the overall number of hospitalisations for infectious diseases before children’s fifth birthday. The association was most explicit for respiratory infections, genitourinary infections and perinatal infections. In contrast, the association between overweight during pregnancy and hospitalisations for infectious diseases was weaker and only noteworthy for perinatal infections.
An association between maternal obesity and the overall risk of hospitalisations for infectious diseases was hypothesised since maternal obesity is associated with many detrimental conditions, including preterm births, low birth weight, birth complications and congenital anomalies.10 23 These conditions contribute to a generally increased vulnerability in the offspring including a higher susceptibility to infections. Two previous studies have examined the association between maternal obesity and the overall risk of hospitalisations for infectious diseases. A recent cohort study from Australia including 2807 children reported that children of obese mothers were 2.3 times more likely to be hospitalised for infectious diseases during the first 5 years of life.12 Compared with our study, the stronger association may be due to different ICD-codes used to define ‘infectious diseases’. We used ICD codes with an infectious cause from all ICD-10 chapters, whereas the Australian study only used ICD-codes from the first ICD-10 chapter. In a similar setting to ours, a cohort study of 6022 Danish children found no association between maternal overweight (BMI greater than or equal to 24 kg/m2) and hospitalisations for infectious diseases during early childhood.24 However, an insignificant association (crude IRR 1.11, 95% CI 0.97 to 1.27) was reported. In comparison to these studies, the large study population in our study yield more precise estimates and allowed us to examine the association between maternal weight and specific infectious disease categories.
Overweight and obesity during pregnancy were associated with perinatal infections. Additionally, obesity during pregnancy was also associated with respiratory, genitourinary and enteric infections. The strong association between maternal BMI during pregnancy and perinatal infections was anticipated from previous research for example, both maternal overweight and obesity have been associated with higher infant mortality.4 The associations between maternal obesity and both respiratory and enteric infections can, at least in part, be explained by reduced breastfeeding among obese mothers.25 Breastfeeding decreases the risk for several infectious diseases including respiratory and enteric infections.26 The association between maternal obesity and respiratory infections has been examined in two previous large cohort studies. Our results are consistent with findings from a Taiwanese study that reported an increased risk of pneumonia during the first 6 months for children of mothers with a pre-pregnancy BMI of 24 or higher.11 Additionally, a Norwegian study found an association between maternal obesity and lower respiratory infections during the first 18 months. However, this association did not persist in the adjusted analyses.27 In comparison with our study, these analyses were also adjusted for maternal income, maternal marital status, maternal asthma, parental smoking after birth, breastfeeding and type of daycare. To our knowledge, no previous studies have examined the association between maternal weight during pregnancy and enteric or genitourinary infections during early childhood.
Strengths of this study include the large size of the study population, which allowed us to systematically examine the associations between BMI during pregnancy and risk of hospitalisations for categories of infectious diseases; the use of several high-quality registers which allowed analysis to be adjusted for potential confounders including maternal education level. However, our study has several weaknesses. A large number of individuals had missing data on BMI during pregnancy, the main exposure. Therefore, we used multiple imputation to include individuals with missing data. Estimates after multiple imputation were similar to estimates from complete case analyses indicating no major selection bias due to missing data, under the assumption that data were missing at random.22 Another limitation is the lack of information about breastfeeding, childhood obesity and other potential mediators. Therefore, we did not conduct a mediation analysis of the association between maternal weight during pregnancy and hospitalisations for infectious diseases. Finally, there is a risk of residual confounding due to unmeasured or incompletely measured factors including ethnicity and socioeconomic status.
In conclusion, this study found an association between overweight and obesity during pregnancy and the overall risk of hospitalisations for infectious diseases in early childhood. Thereby, it contributes to the growing evidence about the wide range of adverse outcomes associated with overweight and the need for stepping up policy interventions.
Contributors SV conceptualised and designed the study, performed data analyses and wrote the manuscript. GR contributed to the design, assisted with the statistical analyses and revised the manuscript. S-AS created the database contributed to the design and revised the manuscript. All authors approved the final manuscript.
Funding This study was supported by a grant from the Oskarsfonden (Box 36, 932 51 Bureå, Sweden. Epost: email@example.com).
Competing interests None declared.
Patient consent Not required.
Ethics approval The study was approved by the Regional Ethical Review Board in Umeå (nr 2012-265-31M and 2013-320-32M) and by the MSc Research Ethics Committee at London School of Hygiene Tropical Medicine (nr 10852). The retrieval and use of register data were also approved through a separate review of data safety and confidentiality by Swedish National Board of Health and Welfare and by Statistics Sweden.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The data used in this study were obtained from third parties. It includes sensitive information and some access restrictions apply to the data. Interested researchers need to obtain data directly from National Board of Health and Welfare in Sweden and from Statistics Sweden. Children included in the study were identified in the Medical Birth Register, data on hospitalisations were obtained from the Swedish National Patient Register and data on deaths were obtained from the Cause of Death Register. All of these registers are maintained by National Board of Health and Welfare in Sweden. Data on maternal education were obtained from the Longitudinal Integration Database for Health Insurance and Labour market Studies and data on migration were obtained from the Swedish Total Population Register, both registers are maintained by Statistics Sweden.