Original Article

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HIRA Research 2024; 4(2): 214-224

Published online November 28, 2024

https://doi.org/10.52937/hira.24.4.2.e6

© Health Insurance Review & Assessment Service

Association between Types of Diabetes and Amniotic Fluid Disorders during Pregnancy: A Cohort Study in South Korea

Soo Hyun Kang1,* , Minah Park2,* , Jong Youn Moon3,4 , Suk Young Kim5

1Gachon Biomedical and Convergence Institute, Gachon University Gil Medical Center, Incheon; 2Department of Ophthalmology, Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan; 3Department of Preventive Medicine, Gachon University College of Medicine; 4Artificial Intelligence and Big-Data Convergence Center; 5Department of Obstetrics and Gynecology, Gachon University Gil Medical Center, Incheon, Korea

Correspondence to :
Jong Youn Moon
Department of Preventive Medicine, Gachon University College of Medicine, 38-13 Dokjeom-ro 3beon-gil, Namdong-gu, Incheon 21565, Korea Tel: +82-32-460-2051
Fax: +82-32-458-2608
E-mail: moonjy@gachon.ac.kr

Suk Young Kim
Department of Obstetrics and Gynecology, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea
Tel: +82-32-458-2832
Fax: +82-32-458-2619
E-mail: ksyob@gilhospital.com

* These authors contributed equally to this work as first authors.

Received: October 14, 2024; Revised: November 22, 2024; Accepted: November 25, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: As the prevalence of maternal diabetes (both pre-pregnancy- and pregnancy-related) is rising, studies on amniotic fluid disorders related to maternal diabetes are necessary. This study aimed to examine whether the type of diabetes affects the risk of amniotic fluid disorders during pregnancy.
Methods: Data from the South Korean NHIS-NHID (National Health Insurance Service National Information Database) from 2010 to 2015 were used in this study. Participants were classified into the following five groups: type 1 diabetes, type 2 diabetes, other types of diabetes, gestational diabetes, and without diabetes. Amniotic fluid disorders included polyhydramnios and oligohydremia. Logistic regression analysis was performed to examine the significance of the association between the types of diabetes and amniotic fluid disorders.
Results: A total of 1,526,365 women gave birth between 2011 and 2015. Those with gestational diabetes, type 1 diabetes, and type 2 diabetes were more likely to develop amniotic fluid disorders compared to those with no diabetic history (gestational diabetes: odds ratio [OR] 1.19, 95% confidence interval [CI] 1.16–1.21; type 1 diabetes: OR 1.30, 95% CI 1.12–1.51; type 2 diabetes: OR 1.26, 95% CI 1.21-1.31). Furthermore, there was an increased probability of developing type 1 diabetes among pregnant women younger than 20 years of age (OR 6.62, 95% CI 2.11–20.83).
Conclusion: Our findings suggest that regardless of the type of diabetes, those with type 1 diabetes, type 2 diabetes, or gestational diabetes were more likely to develop amniotic fluid disorders. Therefore, monitoring diabetes in pregnant women is necessary as it is vital for the health of the fetus and the pregnant woman.

Keywords: Amniotic fluid; Diabetes mellitus; Diabetes, gestational; Pregnancy

The amniotic fluid is responsible for supporting and protecting the fetus during pregnancy [1]. In addition to containing nutrients and growth factors that facilitate fetal growth, amniotic fluid protects the fetus from external threats, as well as providing a means to access fetal health and maturity [2]. In accordance with the amniotic fluid index (AFI), the amount should range from 5 to 25 cm. In contrast, when it is less than 5 cm, it is considered oligohydramnios, and when it is over 25 cm, it is considered polyhydramnios, which are both dangerous to the fetus [3]. The presence of oligohydraemia reduces the movement of the fetus, slows its growth, and causes deformities, cord compression, and even death depending on the gestational age [4]. In contrast, polyhydramnios often results in placental abruption, macrosomia, umbilical cord prolapse, malposition of the fetus, and compromised respiratory health in the mother [5].

The most frequent medical condition associated with pregnancy is diabetes mellitus (DM), which poses a serious risk to both the mother and the fetus [6]. Pre-existing DM types 1 and 2 are associated with adverse obstetric outcomes such as perinatal mortality and birth defects [7]. For gestational DM, serious complications such as, clavicle fracture, brachial plexus injury and macrosomia are known to occur frequently [8]. In the United States, type 1 or type 2 DM affects 1% to 2% of pregnant women, while gestational DM affects 6% to 9% of pregnant women [9]. Also in South Korea, in the 1990s, the prevalence of gestational DM in Korea ranged from 1.7% to 3.9%; however, in 2007, it rose to 4.1% of pregnant women and thereafter grew by 1% to 2% annually until it reached a reported 12.7% from 2011 to 2015 [10].

DM are on the rise worldwide and South Korea is no exception. Furthermore, Korea is experiencing a surge in geriatric pregnancy due to later marriage [11] and childbirth [12]. Given that both pre-pregnancy DM and pregnancy-related DM become more prevalent and continues to be prevalent there is a need to examine the relationship between the two in further depth.

Although other studies [5,13] saw the observation the relationship between DM and amniotic fluid disorders with DM, it did not distinguish between the types of DM. Additionally, there has also never been a study in South Korea that has evaluated the entire population of pregnant women along with their health insurance history. Thus, we investigated the association between the types of DM and amniotic fluid disorders. Therefore, our study aims to investigate the association between different types of DM (type 1, type 2, and gestational DM) and the incidence of amniotic fluid disorders in a representative cohort of pregnant women in South Korea.

1. Data and study population

The data used in this study were obtained from the South Korean National Health Insurance Service National Information Database (NHIS-NHID) from 2002 to 2020. The NHIS offers a range of assistance to help academic and policy health and medical research. The NHID contains information on the insured’s eligibility, insurance rates, medical examination results, treatment specifics based on claim data, details on medical facilities, etc. for the years 2002 through 2020 [14]. A customized dataset from the NHIS (NHIS-2023-2-155) was used for the study’s purposes, which contained substantial data on South Korean women who had given birth between 2011 and 2015. Information that could be used to identify specific participants either during or after data collection is not available to the authors. The period of analysis for the customized data was January 4, 2023 to February 8, 2023. We took 3,272,358 people with claims containing delivery-related codes (procedure codes, DRG [diagnosis-related group] codes, or ICD-10 [International Classification of Diseases 10th revision] codes) between 2011 and 2015. A total of 1,745,993 people who were born or had stillbirth or miscarriage between 2011 and 2015 or whose birth year information was missing were not included. Overall, the final 1,526,365 women who gave birth between 2011 and 2015 (Figure 1).

Fig. 1.Flowchart of study population. NHIS-NHID, National Health Insurance Service National Information Database.

This study was approved by the Institutional Review Board (IRB) of Gachon University Gil Medical Center (IRB No. GCIRB2022-086) and adheres to the tenets of the Declaration of Helsinki (2013). The NHIS-NHID data do not contain any identifying information; hence, additional approval for written informed consent was not required.

2. Variables

The variable of the interest in this study was the types of DM. DM were categorized into 5 types according to the ICD-10 codes; type 1 DM (ICD-10 code: ‘E10’), type 2 DM (ICD-10 code: ‘E11’), gestational DM (ICD-10 code: ‘O24.4’), other DM (ICD-10 code: ‘E12’, ‘E13’, ‘E14’, and ‘O24’) and those who were never diagnosed as no-DM. The date of delivery was used to establish the DM diagnosis. The index delivery for each person was the date of the first claim confirming delivery. By deducting 294 days (42 weeks) from the delivery date of the index, the date of conception was determined. Then, we identified people who had ever been diagnosed as DM before their date of conception. In cases where multiple types of pre-pregnancy DM were identified, we prioritized definitions in the order of type 1, type 2, and other diabetes DM. Among individuals without pre-pregnancy DM, we identified cases of gestational DM occurring within the interval between the date of conception and the index delivery. The primary dependent variable was the amniotic fluid disorders. We identified individuals who were diagnosed with polyhydramnios (ICD-10: O40) or oligohydramnios (ICD-10: O41). The other covariates include age (those under 20 years, 20-29 years, 30-39 years, those over 40 years), national medical insurance status (corporate, regional, medical aid), area of residence (capital, metropolitan, others), maternal year (2010, 2011, 2012, 2013, 2014, and 2015), caesarean section, fetal malformations and breech presentation.

3. Statistical analyses

The study population’s overall characteristics were determined using chi-squared tests and univariate analysis. A logistic regression analysis was used to determine the association between the types of DM and amniotic fluid disorders, while adjusting for covariates. Odds ratio (OR) and 95% confidence interval (CI) were used to report the results. We conducted a stratified subgroup analysis using the adjustment variables from the primary analysis to assess differential effects across specific subgroups. All the statistical analyses were performed using SAS version 9.4 Enterprise (SAS Institute, Cary, NC, USA), and all the p-values were two-sided with a significance level of 0.05.

1. General characteristics

Table 1 presents the result of the general characteristics according to the types of DM. Among the 1,526,365 participants, those without DM were 1,190,660 participants (78.0%). Those with DM are as follows; type 1 DM, 2,908 participants (0.2%); type 2 DM, 45,281 participants (3.0%); other DM, 97,364 participants (6.4%); and gestational DM, 190,153 participants (12.5%). The prevalence of amniotic fluid disorder varied among diabetes subgroups (p<0.0001), with the highest rates observed in type 1 diabetes (6.0%) and type 2 diabetes (5.9%), followed by gestational diabetes (5.5%), non-diabetes history (4.7%), and other diabetes (4.5%).

Table 1 . General characteristics of the study population

VariableGestational DMType 1 DMType 2 DMOther DMNo-DMp-value
n%n%n%n%n%
Total (n=1,526,365)190,15312.52,9080.245,2813.097,3636.41,190,66078.0
Age (yr)<0.0001
<204430.2160.6950.2850.19,4130.8
20-2945,95524.278026.811,29925.016,92417.4451,46437.9
30-39137,49372.32,01369.232,00370.776,93479.0706,12759.3
≥406,2623.3993.41,8844.23,4203.523,6562.0
National Medical Insurance status<0.0001
Corporate142,62675.02,13373.333,03973.073,46575.5887,85774.6
Regional46,56024.573525.311,71325.923,26423.9293,82024.7
Medical aid9670.5401.45291.26340.78,9830.8
Region<0.0001
Capital96,27350.61,68357.923,88752.849,56750.9602,74050.6
Metropolitan45,57224.047916.58,78819.422,34122.9230,77119.4
Others48,30825.474625.712,60627.825,45526.1357,14930.0
Maternal year<0.0001
201023,77912.547716.46,67814.715,47615.9213,05717.9
201137,71519.860120.79,61221.226,35127.1288,36524.2
201239,72720.970124.19,81021.724,69725.4255,41521.5
201340,00621.052518.18,68219.216,54817.0202,61617.0
201437,97420.047516.38,30518.311,61911.9181,89715.3
201510,9525.81294.42,1944.82,6722.749,3104.1
Caesarean section<0.0001
No114,14260.01,60555.226,05157.560,08861.7788,99866.3
Yes76,01140.01,30344.819,23042.537,27538.3401,66233.7
Fetal malformations<0.0001
No175,92592.52,76595.142,41793.793,71596.31,115,19193.7
Yes14,2287.51434.92,8646.33,6483.775,4696.3
Breech presentation<0.0001
No176,80093.02,68692.441,87492.592,35394.91,114,87093.6
Yes13,3537.02227.63,4077.55,0105.175,7906.4

DM, diabetes mellitus.



2.Association between DM and amniotic fluid disorder

Table 2 presents the result of logistic regression analyses for all the variables. Those with gestational DM, type 1 DM, and type 2 DM had increased odds of amniotic fluid disorders compared to those with no-DM history, respectively (gestational DM: OR 1.19, 95% CI 1.16-1.21; type 1 DM: OR 1.30, 95% CI 1.12-1.51; type 2 DM: OR 1.26, 95% CI 1.21-1.31). However, those other types of DM were not statistically significant.

Table 2 . Association between types of diabetes mellitus (DM) and amniotic fluid disorders

VariableAmniotic fluid disorders
OR95% CI
DM
Gestational DM1.191.16–1.21
Type 1 DM1.301.12–1.51
Type 2 DM1.261.21–1.31
Other DM0.990.96–1.02
No-DM1.00
Age (yr)
<201.00
20-290.940.86–1.03
30-390.910.83–1.00
≥401.201.09–1.33
National Medical Insurance status
Corporate1.00
Regional1.031.01–1.04
Medical aid1.060.97–1.15
Area of residence
Capital1.00
Metropolitan0.930.91–0.95
Others1.031.01–1.05
Maternal year
20101.00
20111.031.01–1.06
20121.121.10–1.15
20131.151.12–1.18
20141.141.11–1.17
20151.141.10–1.19
Caesarean section
No1.00
Yes1.031.01–1.05
Fetal malformations
No1.00
Yes1.321.28–1.35
Breech presentation
No1.00
Yes1.151.12–1.19

OR, odds ratio; CI, confidence interval.



3.Association according to socioeconomic and health-related variables

Table 3 presents the results of the subgroup analysis stratified by socioeconomic variables, providing additional insights into subgroup differences and the robustness of the observed association. Among mothers aged under 20 (OR 6.62, 95% CI 2.11–20.83) and those with medical aid insurance (OR 2.79, 95% CI 1.08–7.20) and a breech presentation (OR 1.66, 95% CI 1.03–2.65), the risk in mothers with type 1 DM was higher compared to those among older aged women or those with other medical insurance or without breech presentation. Among individuals with medical aid insurance, mothers with type 1 DM were more likely to have amniotic fluid disorders compared to no-DM (OR 1.54, 95% CI 1.09–2.18).

Table 3 . Association between diabetes mellitus (DM) and amniotic fluid disorders by socioeconomic and health-related variables

VariableGestational DMType 1 DMType 2 DMOther DM
OR*95% CIOR*95% CIOR*95% CIOR*95% CI
Age (yr)
<201.150.76–1.736.622.11–20.831.350.62–2.941.410.61–3.27
20–291.141.09–1.191.641.26–2.141.301.20–1.400.960.89–1.04
30–391.211.18–1.241.150.95–1.401.261.20–1.320.990.96–1.03
≥401.161.04–1.301.000.44–2.301.120.93–1.351.120.97–1.30
National Medical Insurance status
Corporate1.181.15–1.211.231.02–1.471.241.18–1.300.980.95–1.02
Regional1.211.16–1.271.441.07–1.921.291.20–1.401.020.95–1.08
Medical aid1.180.88–1.582.791.08–7.201.541.09–2.180.840.55–1.27
Area of residence
Capital1.171.14–1.211.291.05–1.581.211.14–1.280.980.94–1.02
Metropolitan1.281.22–1.341.471.01–2.121.361.24–1.491.060.99–1.13
Others1.141.10–1.191.230.91–1.671.281.19–1.380.960.90–1.02
Maternal year
20101.231.16–1.311.090.71–1.671.381.25–1.541.050.97–1.14
20111.221.16–1.281.681.23–2.291.171.06–1.280.990.93–1.06
20121.181.13–1.241.200.87–1.651.251.15–1.360.920.86–0.98
20131.071.02–1.121.561.13–2.161.181.07–1.290.960.89–1.04
20141.291.23–1.351.180.80–1.741.301.19–1.431.101.01–1.20
20151.141.04–1.250.460.15–1.451.491.26–1.761.030.86–1.23
Caesarean section
No1.191.16–1.231.381.12–1.691.281.21–1.351.030.99–1.07
Yes1.181.14–1.221.220.97–1.541.241.17–1.320.950.90–1.00
Fetal malformations
No1.201.17–1.231.331.14–1.561.271.22–1.330.990.96–1.02
Yes1.111.04–1.200.910.44–1.851.150.99–1.331.100.96–1.26
Breech presentation
No1.191.16–1.211.271.08–1.491.261.21–1.310.980.95–1.01
Yes1.191.10–1.291.661.03–2.651.241.08–1.421.100.97–1.24

OR, odds ratio; CI, confidence interval.

*Adjusted for covariates.


In this study, we examined the association between the types of DM and amniotic fluid disorders. Our results showed that those with regardless of the types of DM, those with type 1 DM, type 2 DM, gestational DM had higher odds of amniotic fluid disorders. Notably, the association between type 1 or type 2 DM and the risk of amniotic fluid disorders was stronger among under 20 years of age mothers or those covered by medical aid insurance, compared to mothers in older age or with other medical insurance types.

Our study results, along with other studies, provide further support to the growing body of evidence of that DM regardless of type has an impact on amniotic fluid disorders. A study by Bicocca et al. [13] observed that DM increases the odds of polyhydramnios by 290% and oligohydramnios by 26% when using the gestational age-specific AFI. McMahon et al. [15] analyzed the amniotic fluid in women with a gestational DM and found that both oligohydramnios and polyhydramnios occurred more frequently (relative risk [RR] 1.71 and RR 5.94, respectively) compared to those that did not have gestational DM.

Although there is no definite pathology regarding the development of amniotic fluid disorders among diabetic pregnancies, there are several proposed mechanisms [16]. Yasuhi et al. [17] hypothesized that polyhydramnios in DM pregnancies, as opposed to controls, was caused by higher fetal urine output in diabetics during the fasting state. In a study on fetal sheep, Smith and Lumbers [18] showed that maternally induced fetal hyperglycemia by glucose infusion results in glycosuria, diuresis, and natriuresis. This demonstrates that prenatal polyuria brought on by fetal hyperglycemia is the most likely cause. A higher amniotic fluid glucose concentration that results in an osmotic gradient and a shift of water into the amniotic cavity is another potential mechanism [19].

While some studies have shown an association between diabetes and oligohydramnios [15], other research [20] has yielded conflicting results, and there is no clear pathological explanation for this relationship. Overall, there is insufficient evidence to optimize the management of women with oligohydramnios, which has led to ongoing issues [21]. However, given that oligohydramnios can pose risks during delivery [22], it is essential to monitor maternal health more closely, especially in women with diabetes.

The subgroup analysis reveals that under the age of 20 had an effect on the relationship between type 1 DM and the risk of amniotic fluid disorders, increasing the risk of amniotic fluid disorders in individuals with type 1 DM and under age of 20 compared to those with type 1 DM in other age groups. This might be a result of socioeconomic problems. This may be caused by the negative health impacts of teen pregnancy as well as other socioeconomic issues. It is already well established that teen pregnancy can lead to major problems like premature birth, low birthweight, and neonatal mortality [23]. Glycemic control affects pregnancy outcomes significantly and is particularly difficult in teens. Adolescents with type 1 DM already struggle with disease management and preventative control [24]. The chances of achieving optimal glycemic control prior to conception may be diminished by unplanned pregnancy; however, as the majority of teenage pregnancies are unplanned, particularly in South Korea [25]. Nevertheless, this finding should be interpreted with caution, given the limited number of type 1 DM mothers under 20 years of age (n=16), which may have resulted in an overestimation of the observed risk.

Furthermore, medical aid insurance influences the relationship between type 1 and type 2 DM and the risk of amniotic fluid disorders. Socioeconomic factors are likely to contributed to these results. Type 2 DM may have received less attentive care historically and currently than type 1 DM because it was once thought to be a less dangerous condition [26]. This could cause despite the need to switch their regimen to insulin, not to take the necessary action before and after pregnancy [27].

There are important limitations to our study. First, due to the use of the claim data, other potential variables such as glucose logs or HbA1C values could not be seen. Also, when defining amniotic fluid disorders, indexes such as AFI or deepest vertical pocket centiles could not be used. Second, as reported in a prior study [28], the accuracy of the diagnostic information may have been constrained by the inaccurate claims’ diagnosis. However, to improve diagnostic precision, the primary and secondary diagnostic codes were included. Further studies should take these limitations into account in future research. Regardless, this study has several strengths. First, by using the NHIS-NHID data, research on the entire population who gave birth between 2011 and 2015 was possible. Through this, we were able to determine the relationship and the prevalence of amniotic fluid disorders as well as DM in pregnant women. Furthermore, the results of our research can be generalized to the population among pregnant women.

Our findings suggest that regardless of the type of diabetes—whether type 1, type 2, or gestational DM—women with diabetes have higher odds of developing amniotic fluid disorders. Given that DM can impact both the mother and the baby, it is crucial to implement practical, hands-on measures for monitoring women with any form of DM during pregnancy. This is essential for safeguarding the health of both the fetus and the mother.

No potential conflict of interest relevant to this article was reported.

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  24. Cooper AG, Cooper BA. The burden and benefits of teenage life with type 1 diabetes. Mo Med. 2016;113(5):347-50.
  25. Shin JH, Bauer S, Yoon YS, Jeong HC, Rhie YJ, Lee JH, et al. Obstetric and neonatal outcomes of the teenage pregnancy. J Korean Soc Neonatol. 2010;17(1):94-101.
  26. Dunne F. Type 2 diabetes and pregnancy. Semin Fetal Neonatal Med. 2005;10(4):333-9. DOI: https://doi.org/10.1016/j.siny.2005.04.007
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  27. Macintosh MC, Fleming KM, Bailey JA, Doyle P, Modder J, Acolet D, et al. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ. 2006;333(7560):177. DOI: https://doi.org/10.1136/bmj.38856.692986.ae
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  28. Park E, Jang S, Jeon S, Lee S, Lee J, Choi D. Evaluating the consistency of health insurance claim disease code and medical record and improvement plan. Wonju: Health Insurance Review & Assessment Service; 2017. Report No., G000DL1-2017-151.
    Available from: https://repository.hira.or.kr/handle/2019.oak/730

Article

Original Article

HIRA Research 2024; 4(2): 214-224

Published online November 30, 2024 https://doi.org/10.52937/hira.24.4.2.e6

Copyright © Health Insurance Review & Assessment Service.

Association between Types of Diabetes and Amniotic Fluid Disorders during Pregnancy: A Cohort Study in South Korea

Soo Hyun Kang1,* , Minah Park2,* , Jong Youn Moon3,4 , Suk Young Kim5

1Gachon Biomedical and Convergence Institute, Gachon University Gil Medical Center, Incheon; 2Department of Ophthalmology, Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan; 3Department of Preventive Medicine, Gachon University College of Medicine; 4Artificial Intelligence and Big-Data Convergence Center; 5Department of Obstetrics and Gynecology, Gachon University Gil Medical Center, Incheon, Korea

Correspondence to:Jong Youn Moon
Department of Preventive Medicine, Gachon University College of Medicine, 38-13 Dokjeom-ro 3beon-gil, Namdong-gu, Incheon 21565, Korea Tel: +82-32-460-2051
Fax: +82-32-458-2608
E-mail: moonjy@gachon.ac.kr

Suk Young Kim
Department of Obstetrics and Gynecology, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea
Tel: +82-32-458-2832
Fax: +82-32-458-2619
E-mail: ksyob@gilhospital.com

* These authors contributed equally to this work as first authors.

Received: October 14, 2024; Revised: November 22, 2024; Accepted: November 25, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: As the prevalence of maternal diabetes (both pre-pregnancy- and pregnancy-related) is rising, studies on amniotic fluid disorders related to maternal diabetes are necessary. This study aimed to examine whether the type of diabetes affects the risk of amniotic fluid disorders during pregnancy.
Methods: Data from the South Korean NHIS-NHID (National Health Insurance Service National Information Database) from 2010 to 2015 were used in this study. Participants were classified into the following five groups: type 1 diabetes, type 2 diabetes, other types of diabetes, gestational diabetes, and without diabetes. Amniotic fluid disorders included polyhydramnios and oligohydremia. Logistic regression analysis was performed to examine the significance of the association between the types of diabetes and amniotic fluid disorders.
Results: A total of 1,526,365 women gave birth between 2011 and 2015. Those with gestational diabetes, type 1 diabetes, and type 2 diabetes were more likely to develop amniotic fluid disorders compared to those with no diabetic history (gestational diabetes: odds ratio [OR] 1.19, 95% confidence interval [CI] 1.16–1.21; type 1 diabetes: OR 1.30, 95% CI 1.12–1.51; type 2 diabetes: OR 1.26, 95% CI 1.21-1.31). Furthermore, there was an increased probability of developing type 1 diabetes among pregnant women younger than 20 years of age (OR 6.62, 95% CI 2.11–20.83).
Conclusion: Our findings suggest that regardless of the type of diabetes, those with type 1 diabetes, type 2 diabetes, or gestational diabetes were more likely to develop amniotic fluid disorders. Therefore, monitoring diabetes in pregnant women is necessary as it is vital for the health of the fetus and the pregnant woman.

Keywords: Amniotic fluid; Diabetes mellitus; Diabetes, gestational; Pregnancy

INTRODUCTION

The amniotic fluid is responsible for supporting and protecting the fetus during pregnancy [1]. In addition to containing nutrients and growth factors that facilitate fetal growth, amniotic fluid protects the fetus from external threats, as well as providing a means to access fetal health and maturity [2]. In accordance with the amniotic fluid index (AFI), the amount should range from 5 to 25 cm. In contrast, when it is less than 5 cm, it is considered oligohydramnios, and when it is over 25 cm, it is considered polyhydramnios, which are both dangerous to the fetus [3]. The presence of oligohydraemia reduces the movement of the fetus, slows its growth, and causes deformities, cord compression, and even death depending on the gestational age [4]. In contrast, polyhydramnios often results in placental abruption, macrosomia, umbilical cord prolapse, malposition of the fetus, and compromised respiratory health in the mother [5].

The most frequent medical condition associated with pregnancy is diabetes mellitus (DM), which poses a serious risk to both the mother and the fetus [6]. Pre-existing DM types 1 and 2 are associated with adverse obstetric outcomes such as perinatal mortality and birth defects [7]. For gestational DM, serious complications such as, clavicle fracture, brachial plexus injury and macrosomia are known to occur frequently [8]. In the United States, type 1 or type 2 DM affects 1% to 2% of pregnant women, while gestational DM affects 6% to 9% of pregnant women [9]. Also in South Korea, in the 1990s, the prevalence of gestational DM in Korea ranged from 1.7% to 3.9%; however, in 2007, it rose to 4.1% of pregnant women and thereafter grew by 1% to 2% annually until it reached a reported 12.7% from 2011 to 2015 [10].

DM are on the rise worldwide and South Korea is no exception. Furthermore, Korea is experiencing a surge in geriatric pregnancy due to later marriage [11] and childbirth [12]. Given that both pre-pregnancy DM and pregnancy-related DM become more prevalent and continues to be prevalent there is a need to examine the relationship between the two in further depth.

Although other studies [5,13] saw the observation the relationship between DM and amniotic fluid disorders with DM, it did not distinguish between the types of DM. Additionally, there has also never been a study in South Korea that has evaluated the entire population of pregnant women along with their health insurance history. Thus, we investigated the association between the types of DM and amniotic fluid disorders. Therefore, our study aims to investigate the association between different types of DM (type 1, type 2, and gestational DM) and the incidence of amniotic fluid disorders in a representative cohort of pregnant women in South Korea.

METHODS

1. Data and study population

The data used in this study were obtained from the South Korean National Health Insurance Service National Information Database (NHIS-NHID) from 2002 to 2020. The NHIS offers a range of assistance to help academic and policy health and medical research. The NHID contains information on the insured’s eligibility, insurance rates, medical examination results, treatment specifics based on claim data, details on medical facilities, etc. for the years 2002 through 2020 [14]. A customized dataset from the NHIS (NHIS-2023-2-155) was used for the study’s purposes, which contained substantial data on South Korean women who had given birth between 2011 and 2015. Information that could be used to identify specific participants either during or after data collection is not available to the authors. The period of analysis for the customized data was January 4, 2023 to February 8, 2023. We took 3,272,358 people with claims containing delivery-related codes (procedure codes, DRG [diagnosis-related group] codes, or ICD-10 [International Classification of Diseases 10th revision] codes) between 2011 and 2015. A total of 1,745,993 people who were born or had stillbirth or miscarriage between 2011 and 2015 or whose birth year information was missing were not included. Overall, the final 1,526,365 women who gave birth between 2011 and 2015 (Figure 1).

Figure 1. Flowchart of study population. NHIS-NHID, National Health Insurance Service National Information Database.

This study was approved by the Institutional Review Board (IRB) of Gachon University Gil Medical Center (IRB No. GCIRB2022-086) and adheres to the tenets of the Declaration of Helsinki (2013). The NHIS-NHID data do not contain any identifying information; hence, additional approval for written informed consent was not required.

2. Variables

The variable of the interest in this study was the types of DM. DM were categorized into 5 types according to the ICD-10 codes; type 1 DM (ICD-10 code: ‘E10’), type 2 DM (ICD-10 code: ‘E11’), gestational DM (ICD-10 code: ‘O24.4’), other DM (ICD-10 code: ‘E12’, ‘E13’, ‘E14’, and ‘O24’) and those who were never diagnosed as no-DM. The date of delivery was used to establish the DM diagnosis. The index delivery for each person was the date of the first claim confirming delivery. By deducting 294 days (42 weeks) from the delivery date of the index, the date of conception was determined. Then, we identified people who had ever been diagnosed as DM before their date of conception. In cases where multiple types of pre-pregnancy DM were identified, we prioritized definitions in the order of type 1, type 2, and other diabetes DM. Among individuals without pre-pregnancy DM, we identified cases of gestational DM occurring within the interval between the date of conception and the index delivery. The primary dependent variable was the amniotic fluid disorders. We identified individuals who were diagnosed with polyhydramnios (ICD-10: O40) or oligohydramnios (ICD-10: O41). The other covariates include age (those under 20 years, 20-29 years, 30-39 years, those over 40 years), national medical insurance status (corporate, regional, medical aid), area of residence (capital, metropolitan, others), maternal year (2010, 2011, 2012, 2013, 2014, and 2015), caesarean section, fetal malformations and breech presentation.

3. Statistical analyses

The study population’s overall characteristics were determined using chi-squared tests and univariate analysis. A logistic regression analysis was used to determine the association between the types of DM and amniotic fluid disorders, while adjusting for covariates. Odds ratio (OR) and 95% confidence interval (CI) were used to report the results. We conducted a stratified subgroup analysis using the adjustment variables from the primary analysis to assess differential effects across specific subgroups. All the statistical analyses were performed using SAS version 9.4 Enterprise (SAS Institute, Cary, NC, USA), and all the p-values were two-sided with a significance level of 0.05.

RESULTS

1. General characteristics

Table 1 presents the result of the general characteristics according to the types of DM. Among the 1,526,365 participants, those without DM were 1,190,660 participants (78.0%). Those with DM are as follows; type 1 DM, 2,908 participants (0.2%); type 2 DM, 45,281 participants (3.0%); other DM, 97,364 participants (6.4%); and gestational DM, 190,153 participants (12.5%). The prevalence of amniotic fluid disorder varied among diabetes subgroups (p<0.0001), with the highest rates observed in type 1 diabetes (6.0%) and type 2 diabetes (5.9%), followed by gestational diabetes (5.5%), non-diabetes history (4.7%), and other diabetes (4.5%).

Table 1 . General characteristics of the study population.

VariableGestational DMType 1 DMType 2 DMOther DMNo-DMp-value
n%n%n%n%n%
Total (n=1,526,365)190,15312.52,9080.245,2813.097,3636.41,190,66078.0
Age (yr)<0.0001
<204430.2160.6950.2850.19,4130.8
20-2945,95524.278026.811,29925.016,92417.4451,46437.9
30-39137,49372.32,01369.232,00370.776,93479.0706,12759.3
≥406,2623.3993.41,8844.23,4203.523,6562.0
National Medical Insurance status<0.0001
Corporate142,62675.02,13373.333,03973.073,46575.5887,85774.6
Regional46,56024.573525.311,71325.923,26423.9293,82024.7
Medical aid9670.5401.45291.26340.78,9830.8
Region<0.0001
Capital96,27350.61,68357.923,88752.849,56750.9602,74050.6
Metropolitan45,57224.047916.58,78819.422,34122.9230,77119.4
Others48,30825.474625.712,60627.825,45526.1357,14930.0
Maternal year<0.0001
201023,77912.547716.46,67814.715,47615.9213,05717.9
201137,71519.860120.79,61221.226,35127.1288,36524.2
201239,72720.970124.19,81021.724,69725.4255,41521.5
201340,00621.052518.18,68219.216,54817.0202,61617.0
201437,97420.047516.38,30518.311,61911.9181,89715.3
201510,9525.81294.42,1944.82,6722.749,3104.1
Caesarean section<0.0001
No114,14260.01,60555.226,05157.560,08861.7788,99866.3
Yes76,01140.01,30344.819,23042.537,27538.3401,66233.7
Fetal malformations<0.0001
No175,92592.52,76595.142,41793.793,71596.31,115,19193.7
Yes14,2287.51434.92,8646.33,6483.775,4696.3
Breech presentation<0.0001
No176,80093.02,68692.441,87492.592,35394.91,114,87093.6
Yes13,3537.02227.63,4077.55,0105.175,7906.4

DM, diabetes mellitus..



2.Association between DM and amniotic fluid disorder

Table 2 presents the result of logistic regression analyses for all the variables. Those with gestational DM, type 1 DM, and type 2 DM had increased odds of amniotic fluid disorders compared to those with no-DM history, respectively (gestational DM: OR 1.19, 95% CI 1.16-1.21; type 1 DM: OR 1.30, 95% CI 1.12-1.51; type 2 DM: OR 1.26, 95% CI 1.21-1.31). However, those other types of DM were not statistically significant.

Table 2 . Association between types of diabetes mellitus (DM) and amniotic fluid disorders.

VariableAmniotic fluid disorders
OR95% CI
DM
Gestational DM1.191.16–1.21
Type 1 DM1.301.12–1.51
Type 2 DM1.261.21–1.31
Other DM0.990.96–1.02
No-DM1.00
Age (yr)
<201.00
20-290.940.86–1.03
30-390.910.83–1.00
≥401.201.09–1.33
National Medical Insurance status
Corporate1.00
Regional1.031.01–1.04
Medical aid1.060.97–1.15
Area of residence
Capital1.00
Metropolitan0.930.91–0.95
Others1.031.01–1.05
Maternal year
20101.00
20111.031.01–1.06
20121.121.10–1.15
20131.151.12–1.18
20141.141.11–1.17
20151.141.10–1.19
Caesarean section
No1.00
Yes1.031.01–1.05
Fetal malformations
No1.00
Yes1.321.28–1.35
Breech presentation
No1.00
Yes1.151.12–1.19

OR, odds ratio; CI, confidence interval..



3.Association according to socioeconomic and health-related variables

Table 3 presents the results of the subgroup analysis stratified by socioeconomic variables, providing additional insights into subgroup differences and the robustness of the observed association. Among mothers aged under 20 (OR 6.62, 95% CI 2.11–20.83) and those with medical aid insurance (OR 2.79, 95% CI 1.08–7.20) and a breech presentation (OR 1.66, 95% CI 1.03–2.65), the risk in mothers with type 1 DM was higher compared to those among older aged women or those with other medical insurance or without breech presentation. Among individuals with medical aid insurance, mothers with type 1 DM were more likely to have amniotic fluid disorders compared to no-DM (OR 1.54, 95% CI 1.09–2.18).

Table 3 . Association between diabetes mellitus (DM) and amniotic fluid disorders by socioeconomic and health-related variables.

VariableGestational DMType 1 DMType 2 DMOther DM
OR*95% CIOR*95% CIOR*95% CIOR*95% CI
Age (yr)
<201.150.76–1.736.622.11–20.831.350.62–2.941.410.61–3.27
20–291.141.09–1.191.641.26–2.141.301.20–1.400.960.89–1.04
30–391.211.18–1.241.150.95–1.401.261.20–1.320.990.96–1.03
≥401.161.04–1.301.000.44–2.301.120.93–1.351.120.97–1.30
National Medical Insurance status
Corporate1.181.15–1.211.231.02–1.471.241.18–1.300.980.95–1.02
Regional1.211.16–1.271.441.07–1.921.291.20–1.401.020.95–1.08
Medical aid1.180.88–1.582.791.08–7.201.541.09–2.180.840.55–1.27
Area of residence
Capital1.171.14–1.211.291.05–1.581.211.14–1.280.980.94–1.02
Metropolitan1.281.22–1.341.471.01–2.121.361.24–1.491.060.99–1.13
Others1.141.10–1.191.230.91–1.671.281.19–1.380.960.90–1.02
Maternal year
20101.231.16–1.311.090.71–1.671.381.25–1.541.050.97–1.14
20111.221.16–1.281.681.23–2.291.171.06–1.280.990.93–1.06
20121.181.13–1.241.200.87–1.651.251.15–1.360.920.86–0.98
20131.071.02–1.121.561.13–2.161.181.07–1.290.960.89–1.04
20141.291.23–1.351.180.80–1.741.301.19–1.431.101.01–1.20
20151.141.04–1.250.460.15–1.451.491.26–1.761.030.86–1.23
Caesarean section
No1.191.16–1.231.381.12–1.691.281.21–1.351.030.99–1.07
Yes1.181.14–1.221.220.97–1.541.241.17–1.320.950.90–1.00
Fetal malformations
No1.201.17–1.231.331.14–1.561.271.22–1.330.990.96–1.02
Yes1.111.04–1.200.910.44–1.851.150.99–1.331.100.96–1.26
Breech presentation
No1.191.16–1.211.271.08–1.491.261.21–1.310.980.95–1.01
Yes1.191.10–1.291.661.03–2.651.241.08–1.421.100.97–1.24

OR, odds ratio; CI, confidence interval..

*Adjusted for covariates..


DISCUSSION

In this study, we examined the association between the types of DM and amniotic fluid disorders. Our results showed that those with regardless of the types of DM, those with type 1 DM, type 2 DM, gestational DM had higher odds of amniotic fluid disorders. Notably, the association between type 1 or type 2 DM and the risk of amniotic fluid disorders was stronger among under 20 years of age mothers or those covered by medical aid insurance, compared to mothers in older age or with other medical insurance types.

Our study results, along with other studies, provide further support to the growing body of evidence of that DM regardless of type has an impact on amniotic fluid disorders. A study by Bicocca et al. [13] observed that DM increases the odds of polyhydramnios by 290% and oligohydramnios by 26% when using the gestational age-specific AFI. McMahon et al. [15] analyzed the amniotic fluid in women with a gestational DM and found that both oligohydramnios and polyhydramnios occurred more frequently (relative risk [RR] 1.71 and RR 5.94, respectively) compared to those that did not have gestational DM.

Although there is no definite pathology regarding the development of amniotic fluid disorders among diabetic pregnancies, there are several proposed mechanisms [16]. Yasuhi et al. [17] hypothesized that polyhydramnios in DM pregnancies, as opposed to controls, was caused by higher fetal urine output in diabetics during the fasting state. In a study on fetal sheep, Smith and Lumbers [18] showed that maternally induced fetal hyperglycemia by glucose infusion results in glycosuria, diuresis, and natriuresis. This demonstrates that prenatal polyuria brought on by fetal hyperglycemia is the most likely cause. A higher amniotic fluid glucose concentration that results in an osmotic gradient and a shift of water into the amniotic cavity is another potential mechanism [19].

While some studies have shown an association between diabetes and oligohydramnios [15], other research [20] has yielded conflicting results, and there is no clear pathological explanation for this relationship. Overall, there is insufficient evidence to optimize the management of women with oligohydramnios, which has led to ongoing issues [21]. However, given that oligohydramnios can pose risks during delivery [22], it is essential to monitor maternal health more closely, especially in women with diabetes.

The subgroup analysis reveals that under the age of 20 had an effect on the relationship between type 1 DM and the risk of amniotic fluid disorders, increasing the risk of amniotic fluid disorders in individuals with type 1 DM and under age of 20 compared to those with type 1 DM in other age groups. This might be a result of socioeconomic problems. This may be caused by the negative health impacts of teen pregnancy as well as other socioeconomic issues. It is already well established that teen pregnancy can lead to major problems like premature birth, low birthweight, and neonatal mortality [23]. Glycemic control affects pregnancy outcomes significantly and is particularly difficult in teens. Adolescents with type 1 DM already struggle with disease management and preventative control [24]. The chances of achieving optimal glycemic control prior to conception may be diminished by unplanned pregnancy; however, as the majority of teenage pregnancies are unplanned, particularly in South Korea [25]. Nevertheless, this finding should be interpreted with caution, given the limited number of type 1 DM mothers under 20 years of age (n=16), which may have resulted in an overestimation of the observed risk.

Furthermore, medical aid insurance influences the relationship between type 1 and type 2 DM and the risk of amniotic fluid disorders. Socioeconomic factors are likely to contributed to these results. Type 2 DM may have received less attentive care historically and currently than type 1 DM because it was once thought to be a less dangerous condition [26]. This could cause despite the need to switch their regimen to insulin, not to take the necessary action before and after pregnancy [27].

There are important limitations to our study. First, due to the use of the claim data, other potential variables such as glucose logs or HbA1C values could not be seen. Also, when defining amniotic fluid disorders, indexes such as AFI or deepest vertical pocket centiles could not be used. Second, as reported in a prior study [28], the accuracy of the diagnostic information may have been constrained by the inaccurate claims’ diagnosis. However, to improve diagnostic precision, the primary and secondary diagnostic codes were included. Further studies should take these limitations into account in future research. Regardless, this study has several strengths. First, by using the NHIS-NHID data, research on the entire population who gave birth between 2011 and 2015 was possible. Through this, we were able to determine the relationship and the prevalence of amniotic fluid disorders as well as DM in pregnant women. Furthermore, the results of our research can be generalized to the population among pregnant women.

Our findings suggest that regardless of the type of diabetes—whether type 1, type 2, or gestational DM—women with diabetes have higher odds of developing amniotic fluid disorders. Given that DM can impact both the mother and the baby, it is crucial to implement practical, hands-on measures for monitoring women with any form of DM during pregnancy. This is essential for safeguarding the health of both the fetus and the mother.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Fig 1.

Figure 1.Flowchart of study population. NHIS-NHID, National Health Insurance Service National Information Database.
HIRA Research 2024; 4: 214-224https://doi.org/10.52937/hira.24.4.2.e6

Table 1 . General characteristics of the study population.

VariableGestational DMType 1 DMType 2 DMOther DMNo-DMp-value
n%n%n%n%n%
Total (n=1,526,365)190,15312.52,9080.245,2813.097,3636.41,190,66078.0
Age (yr)<0.0001
<204430.2160.6950.2850.19,4130.8
20-2945,95524.278026.811,29925.016,92417.4451,46437.9
30-39137,49372.32,01369.232,00370.776,93479.0706,12759.3
≥406,2623.3993.41,8844.23,4203.523,6562.0
National Medical Insurance status<0.0001
Corporate142,62675.02,13373.333,03973.073,46575.5887,85774.6
Regional46,56024.573525.311,71325.923,26423.9293,82024.7
Medical aid9670.5401.45291.26340.78,9830.8
Region<0.0001
Capital96,27350.61,68357.923,88752.849,56750.9602,74050.6
Metropolitan45,57224.047916.58,78819.422,34122.9230,77119.4
Others48,30825.474625.712,60627.825,45526.1357,14930.0
Maternal year<0.0001
201023,77912.547716.46,67814.715,47615.9213,05717.9
201137,71519.860120.79,61221.226,35127.1288,36524.2
201239,72720.970124.19,81021.724,69725.4255,41521.5
201340,00621.052518.18,68219.216,54817.0202,61617.0
201437,97420.047516.38,30518.311,61911.9181,89715.3
201510,9525.81294.42,1944.82,6722.749,3104.1
Caesarean section<0.0001
No114,14260.01,60555.226,05157.560,08861.7788,99866.3
Yes76,01140.01,30344.819,23042.537,27538.3401,66233.7
Fetal malformations<0.0001
No175,92592.52,76595.142,41793.793,71596.31,115,19193.7
Yes14,2287.51434.92,8646.33,6483.775,4696.3
Breech presentation<0.0001
No176,80093.02,68692.441,87492.592,35394.91,114,87093.6
Yes13,3537.02227.63,4077.55,0105.175,7906.4

DM, diabetes mellitus..


Table 2 . Association between types of diabetes mellitus (DM) and amniotic fluid disorders.

VariableAmniotic fluid disorders
OR95% CI
DM
Gestational DM1.191.16–1.21
Type 1 DM1.301.12–1.51
Type 2 DM1.261.21–1.31
Other DM0.990.96–1.02
No-DM1.00
Age (yr)
<201.00
20-290.940.86–1.03
30-390.910.83–1.00
≥401.201.09–1.33
National Medical Insurance status
Corporate1.00
Regional1.031.01–1.04
Medical aid1.060.97–1.15
Area of residence
Capital1.00
Metropolitan0.930.91–0.95
Others1.031.01–1.05
Maternal year
20101.00
20111.031.01–1.06
20121.121.10–1.15
20131.151.12–1.18
20141.141.11–1.17
20151.141.10–1.19
Caesarean section
No1.00
Yes1.031.01–1.05
Fetal malformations
No1.00
Yes1.321.28–1.35
Breech presentation
No1.00
Yes1.151.12–1.19

OR, odds ratio; CI, confidence interval..


Table 3 . Association between diabetes mellitus (DM) and amniotic fluid disorders by socioeconomic and health-related variables.

VariableGestational DMType 1 DMType 2 DMOther DM
OR*95% CIOR*95% CIOR*95% CIOR*95% CI
Age (yr)
<201.150.76–1.736.622.11–20.831.350.62–2.941.410.61–3.27
20–291.141.09–1.191.641.26–2.141.301.20–1.400.960.89–1.04
30–391.211.18–1.241.150.95–1.401.261.20–1.320.990.96–1.03
≥401.161.04–1.301.000.44–2.301.120.93–1.351.120.97–1.30
National Medical Insurance status
Corporate1.181.15–1.211.231.02–1.471.241.18–1.300.980.95–1.02
Regional1.211.16–1.271.441.07–1.921.291.20–1.401.020.95–1.08
Medical aid1.180.88–1.582.791.08–7.201.541.09–2.180.840.55–1.27
Area of residence
Capital1.171.14–1.211.291.05–1.581.211.14–1.280.980.94–1.02
Metropolitan1.281.22–1.341.471.01–2.121.361.24–1.491.060.99–1.13
Others1.141.10–1.191.230.91–1.671.281.19–1.380.960.90–1.02
Maternal year
20101.231.16–1.311.090.71–1.671.381.25–1.541.050.97–1.14
20111.221.16–1.281.681.23–2.291.171.06–1.280.990.93–1.06
20121.181.13–1.241.200.87–1.651.251.15–1.360.920.86–0.98
20131.071.02–1.121.561.13–2.161.181.07–1.290.960.89–1.04
20141.291.23–1.351.180.80–1.741.301.19–1.431.101.01–1.20
20151.141.04–1.250.460.15–1.451.491.26–1.761.030.86–1.23
Caesarean section
No1.191.16–1.231.381.12–1.691.281.21–1.351.030.99–1.07
Yes1.181.14–1.221.220.97–1.541.241.17–1.320.950.90–1.00
Fetal malformations
No1.201.17–1.231.331.14–1.561.271.22–1.330.990.96–1.02
Yes1.111.04–1.200.910.44–1.851.150.99–1.331.100.96–1.26
Breech presentation
No1.191.16–1.211.271.08–1.491.261.21–1.310.980.95–1.01
Yes1.191.10–1.291.661.03–2.651.241.08–1.421.100.97–1.24

OR, odds ratio; CI, confidence interval..

*Adjusted for covariates..


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