University of Groningen
Pregnancy complications
Fitria, Najmiatul
DOI:
10.33612/diss.167808473
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Publication date: 2021
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Fitria, N. (2021). Pregnancy complications: health economics of screening and prevention. University of Groningen. https://doi.org/10.33612/diss.167808473
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This thesis aimed to assess the health economic impact of using MMN (Multiple Micro-Nutrient) and impact of hyperglycemia during pregnancy, from both epidemiological and economic perspective. Furthermore, it aimed to evaluate strategies directed at improving health in pregnancy. To this end, a number of studies have been conducted. Chapter 2 assessed the hyperglycemia burden first detected in pregnancy among Indonesian women. Meanwhile, chapter 3 reviewed evidence on the cost-effectiveness of controlling gestational diabetes mellitus, and chapter 4 explored the potential benefit of MMN in the prevention of pregnancy complications. Therefore, over a broad range of perinatal issues, an epidemiological study, meta-analysis, and a cost-effectiveness study was conducted. Furthermore, a paper was added in chapter 5 regarding the properties of dadiah as traditional food and supplementation.
Peri-conceptional services including pregnancy, childbirth, and contraception aim to enhance maternal health, which will in turn improve the health of newborns (1,2). Healthy pregnancies and newborns will significantly strengthen the health and economic potentials of a generation. In fact, it has been demonstrated that healthy growth starts at conception (3). In the short run, reproductive health services can reduce the risk of pregnancy complications, thereby directly lowering morbidity and mortality rates for mothers and newborns. Therefore, the Indonesian government guarantees the availability of health resources and the provision of pre-pregnancy, childbirth, and postnatal health services, as well as the administration of contraceptives, and sexual health services.
Main findings
Nationally, Indonesian society’s access to maternal health services tends to improve. According to the Demographic and Health Survey, the Maternal Mortality Ratio (MMR) showed a downward trend, decreasing from 390 per 100,000 live births in 1997 to 359 per 100,000 live births in 2012 (4). However, when compared to the Sustainable Development Goals (SDGs) target in 2015 of 102 maternal deaths per 100,000 live births, and even <70 by 2030 (3), it is clear that Indonesia still needs extra effort and hard work. The direct cause of maternal death is often associated with complications of pregnancy, childbirth, and the puerperium such as bleeding, preeclampsia/eclampsia, infection, labor, miscarriage, and also with the fact that women give birth to many children at short intervals, up to a relatively high age.
The data were health records of pregnant women who have no pre-existing diabetes and screened for Hyperglycemia First Detected in Pregnancy (HFDP)
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in 2014 and 2015 at two West Sumatera hospitals. These women were grouped into Diabetes In Pregnancy (DIP, glucose 126 mg/dl), Gestational Diabetes Mellitus (GDM, glucose 92-125 mg/dl), and normal glucose levels (glucose < 92 mg/dl), following the World Health Organization (WHO) standard. Meanwhile, maternal mortality in pregnant women with HFDP was around 1.4% (chapter 2), and there were no differences between those admitted in the hospital with normal glucose levels (p 0.648) (chapter 2). Maternal outcomes did not seem to differ between HFDP and normal fasting blood glucose in Indonesian women. However, it should be noted that those with normal fasting blood glucose could still be at risk because there are many factors associated with pregnancy complications.
There were considerable differences between hospital A (in Padang) and B (in Bukittinggi) concerning the number of GDM cases and the number of deaths. This mean that there were substantially more cases of GDM and deaths in Padang. This could be partly explained as a regional difference between Padang and Bukittinggi. However, it might have been triggered by the fact that Padang is a tertiary center, hence a top-referral hospital. Therefore, undetected cases in Bukittinggi were likely detected after referring to Padang. This makes screening to become a necessity in order for treatment to be cost-effective. According to the Indonesian DHS, factors that complicate the process of handling emergency pregnancies include delay in recognizing danger signs, in decision making, in reaching health facilities, and in handling emergency (4-6). Furthermore, other influential factors contributing to maternal mortality are infectious and non-communicable diseases such as hypertension, diabetes mellitus, heart disease, and malnourishment. Also, chronic diseases such as hypertension, diabetes mellitus, heart disease, severe asthma, and mental disorders significantly affect the mother, fetus, and newborn’s health conditions. Unfortunately, management of chronic diseases in pregnant women is still not as expected, and the data are also not properly recorded.
In chapter 3, a review was conducted about the cost-effectiveness of controlling gestational diabetes mellitus. Also, timely screening for hyperglycemia in pregnancy using a simple glucose test enhances early detection and GDM control (7). Improvement in medical treatment has contributed to a rise in healthcare spending (8). This cannot be denied, and the more advanced the test, the higher the costs involved. In countries and settings where the economic evaluations were performed (chapter 3), maternity services and
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guidelines on screening and treating GDM were already well established. Also, neither screening nor treating GDM seems to be convincingly cost-effective from the reviewed studies (Chapter 3). The interventions in the review were dietary advice, lifestyle modification, patient counseling, and in some cases, with insulin combination. However, all studies were conducted in high-income (HIC) countries with obviously different health systems from low-/ middle-income countries (LMIC) (7). The most striking thing here is that HIC has made Hba1c the standard method for testing blood glucose, however LMIC still carry out glucose test using capillary blood (9). Overall, there is an urgent need for well-designed intervention studies in low- and middle-income countries where the global health GDM consequences are most considerable (9).
This thesis raised screening and nutritional issues during pregnancy. It was found that health screening is an essential part at the beginning of pregnancy. Also, previous studies on early screening for gestational diabetes mellitus and pre-eclampsia found that screening could be a potential driver of cost-effectiveness management during pregnancy (7,10).
In this thesis, besides screening issues, malnutrition in pregnancy was also focused on as a contributor to maternal-neonatal mortality. Meanwhile, malnutrition in pregnant women is still a public health problem that needs special attention. In fact, lack of nutritional intake in these women can cause anemia, which will increase bleeding risk and low birth-weight babies. The prevalence of anemia in pregnant women in Indonesia is around 37.1% (5). In addition to the lack of iron intake, anemia can also be caused by helminthiasis and malaria (5,11). Other nutritional problems are lack of chronic energy disease (CED) and iodized salt consumption, which is still low (11). Therefore, pregnant women were given iron-folic acid (IFA) in four visits to the primary public health services prior to delivery. This IFA is still the standard for overcoming anemic cases in Indonesian pregnant women as well as WHO (11-13).
In Chapter 4, the cost-effectiveness of multiple micronutrients (MMN) versus IFA was compared using a health economic model, in particular a decision tree. This was a continuation of the supplementation with multiple micronutrients intervention trials (SUMMIT) in Lombok, Indonesia (14). The effect was measured in disability-adjusted life years (DALYs). Furthermore, the SUMMIT itself was a large scale randomized controlled trial that cooperated
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through the Helen Keller International, Indonesia. The trial was conducted in Lombok, West Nusa Tenggara, to reduce maternal and infant death in routine prenatal care (15). Also, multiple micronutrients contents were compared: (30mg iron (ferrous fumarate), 400µg folic acid, 800µg retinol (retinyl acetate), 200IU vitamin D (ergocalciferol), 10mg vitamin E (alpha-tocopherol acetate), 70mg ascorbic acid, 1.4mg vitamin B1 (thiamine mononitrate), 18mg niacin (niacinamide), 1.9mg vitamin B6 (pyridoxine), 2.6µg vitamin B12 (cyanocobalamin), 15mg zinc (zinc gluconate), 2 mg copper, 65µg selenium, and 150µg iodine were used as intervention. IFA contains 30mg iron (ferrous fumarate), and 400µg folic acid was used as a comparator.
MMN appeared to be more cost-effective compared to IFA. As the willingness to pay to be a one-time gross domestic product (GDP) per capita (I$11812) was set, both MMN and IFA could be used to overcome the anemic and undernourished case in pregnant women. Incrementally, this implies that MMN would avert on average 0.27 DALY per pregnant woman. Furthermore, total costs were higher in the MMN group, with an incremental cost of I$ 75.45. The incremental cost-effectiveness ratio amounted to I$274.73 per DALY averted (chapter 4). Meanwhile, among the factors that influence cost-effectiveness value, the cost for MMN and IFA were found to be crucial. This result is valuable since individual patients’ data were used. This was generalizable to the Indonesian population.
One of the non-medication treatments for reducing pregnancy complications that have also been developed in recent times is probiotics. These probiotics could recover glycemic control and alleviate some of the adverse effects of type 2 diabetes (16-19). However, whether the effects are generalizable to gestational diabetes mellitus (GDM) is still undetermined. Therefore, chapter 5 explored the effects of an Indonesian traditional fermented milk (yogurt-like) product called dadiah, which is consumed by the Minangese in West Sumatera. Lactococcus, Lactobacillus, and Leuconostoc were predominantly
found among the dadiah microbiota using 16S- rRNA gene sequencing. However, the composition of microbial communities (microbiota) inhabiting the dadiah is still mostly unknown (20).
Implications
Reproductive health services aim to meet the right of every pregnant woman to access quality health services. Therefore, they are able to undergo a healthy pregnancy, delivery, and have a healthy baby. In this thesis, some studies about
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methods was conducted, which could give value to the reproductive health services in Indonesia.
Gestational Diabetes Mellitus Screening
The mainstay treatment of GDM is dietary and lifestyle modification, which include weight management, medical nutrition therapy, and physical activity (21). Furthermore, women monitor their fasting and postmeal glucose levels, adjust their individual diet and lifestyle to meet their glycemic targets. Regarding diet, it cannot be denied that consumption in Indonesia is far from healthy, therefore this country is still in the LMIC category. Based on BPS data, there are still many Indonesians with calorie consumption rates below 1400kcal / day. This consumption rate ranges from 8% -27% of the entire provinces (22). Also, blood glucose monitoring is not a mandatory thing to do (11). This is acceptable as long as most pregnant women could carry out self-monitoring of blood glucose (SMBG). This explains that the HFDP number was higher at the last trimester of pregnancy (Chapter 3). Chapter 2 showed that most of GDM screening are already established in HIC. Therefore, setting up GDM screening in Indonesia has become a challenging task, starting with GDM tools, methods, and human resources in healthcare facilities. Also, the total glucose in an oral tolerance test should be standardized, whether 75gr or 100gr. Currently, the recommended blood glucose test is the HbA1c check. Even when the HbA1c examination has become the standard requirement for pregnant women, Indonesia is still unable to fulfill it due to the substantial population and very high price of the examination. In 2016 the Ministry of Health released standard tariff non-capitation for Hba1c, which the government will not afford. For one time, Hba1c testing will cost I$ 10 (More than ten times OGTT screening) (23).
Supplementation during pregnancy
Providing pregnant women with MMN is more cost-effective rather than giving iron-folic acid. These women need more micronutrients to keep them healthy, which is part of antenatal services. Based on health survey, the coverage of pregnant women receiving antenatal services has increased from 92.7% in 2010 to 95.2% in 2013. Furthermore, deliveries assisted by health workers also increased from 79.0% in 2010 to 86.9% in 2013. These data explained that Indonesia still lacks human resources. Even though the price of pregnancy supplementation is cheap, policymakers still need extra effort. Most often, the vitamins obtained from vegetables are not optimal due to the cooking process. In fact, vegetables that are
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left too ripe will cause loss of vitamins the body actually needs. Also, the multiple micronutrients needed by pregnant women are vitamin A, B complex, D, E, Zinc, Calcium, copper, magnesium, selenium, and iodine (24). WHO recommends the addition of supplementation during pregnancy, especially in countries with a high prevalence of nutritional deficiencies (12).
In Chapter 4, the cost-effectiveness of pregnancy supplementation was explained. The price for MMN is around I$ 105 per year compared to IFA which is around I$ 24. Furthermore, the total cost for MMN is almost doubled compared to IFA, but it has ICER I$ 274.73 per DALY averted. This implies that pregnant women need another supplementation besides IFA. Most pregnant women in Indonesia already used MMN, but it is still not covered by national health insurance. Furthermore, ICER in the deterministic sensitivity analysis has shown that MMN is more costly but more effective in reducing DALYs in pregnant women. Therefore, MMN averted 0.27 DALYs per patient on average compared to IFA, at an incremental cost of I$ 75.45.
This study suggested that giving supplementation during pregnancy is essential to reduce nutritional problem. Therefore, both MMN and IFA are effective, but MMN is more cost-effective per DALY averted in pregnant women.
Relevant to the clinical setting.
Despite the importance of medical nutrition therapy and its general recommendation in clinical practice, there are limited data regarding the optimal diet for achieving maternal euglycemia (8–11). Furthermore, it is known that the dietary interventions for achieving maternal glycemia effectively reduce excessive fetal growth. (12).
Pregnant women need to take vitamins and supplements when they experience severe nausea and vomiting in the trimester of pregnancy. Also, the development of food data system, which includes developing a methodology for micronutrient composition in foods, organizing data retrieval, reporting and dissemination through electronic means may affect health and nutrition, with particular emphasis on local foods, which may be necessary for maintaining and developing local cultures.
In this thesis, the safety of dadiah as one of the traditional food was evaluated, and a prospective indigenous healthy food supplementation for pregnant women was ascertained. Furthermore, Dadiah, as a yogurt-like drink, could improve glycemic control, blood lipid profile, and oxidative stress in pregnant
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women with GDM (17). This supplement could also fulfill the daily intake of protein since it is made from buffalo milk. Indonesia, especially the Minang community, needs to be proud to have dadiah. However, evaluating the nutritional impact and cost-benefit of food-based approaches in combating micronutrient deficiencies has not yet been conducted.
These results both on MMN and dadiah can hopefully inspire others to consider the beneficial outcomes of nutritional interventions in economic evaluations, and help decision-makers prioritize financing for nutritional intervention in pregnant women.
Limitations of the thesis
Firstly, there was a lack of reference value for women of childbearing age in the general Indonesian population. Secondly, there was no information available on maternal age and parity for pregnant women in the region. The sample was collected in referral hospitals, whereas most pregnant women in West-Sumatera were managed in primary care.
As for economic evaluation, there was data lack for every step passed by pregnant women. These steps include four times prenatal and three times postnatal visits.
Overall, this resulted from a lack of healthcare facilities in Indonesia. To improve the quality of maternal health services, every health facility needs to have good recording and reporting mechanisms. Furthermore, every health care facility is required to provide services before and during pregnancy, as well as after childbirth. The government guarantees the availability, equity, and affordability of medicines and medical supplies in the provision of pre-pregnancy, pre-pregnancy, childbirth, and postnatal health services. Therefore, to accelerate the achievement of optimal maternal health, community participation is needed.
General conclusion
Integrated antenatal is a comprehensive service provided to all pregnant women to fulfill their right to quality antenatal services. These integrated services should be well established to reach the target of SDGs goal. The services include promotive, preventive, as well as curative and rehabilitative management for pregnant women.
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Every health worker in public or private health facilities needs to provide comprehensive services to ensure a normal pregnancy, early problem detection, and to make adequate interventions. Furthermore, integrated antenatal care guidelines which are dynamic, can be adapted to programs development and the regions specific needs.
Most importantly, assessment and implementation of health management during pregnancy should be strongly encouraged. Even though this thesis described the general condition of pregnant women, it is necessary to address more comprehensive action in clinical and societal settings. Meanwhile, acknowledgment of detailed data is necessary in order to provide results that are close to the real condition from a health economics perspective. In an era where health economics starts to develop, this thesis has contributed to overcoming several pregnancy problems.
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REFERENCES
(1) L. K. Küpers. The first 1000 days and beyond: From early life environment
to epigenetics and childhood overweight. . Groningen: University of
Groningen; 2016.
(2) Fox SE, Levitt P, Nelson CA,3rd. How the timing and quality of early experiences influence the development of brain architecture. Child Dev 2010 Jan-Feb;81(1):28-40.
(3) United Nations Development Programme. Sustainable Development Goals. 2020; Available at: https://www.undp.org/content/undp/en/ home/sustainable-development-goals/goal-3-good-health-and-well-being.html. Accessed June,9, 2020.
(4) Board (BKKBN), and Kementerian Kesehatan (Kemenkes—MOH), and ICF International. ational Population and Family Planning Indonesia Demographic and Health Survey 2012. . 2013.
(5) National Institute of Health Research and Development (NIHRD). Indonesia Basic Health Research (RISKESDAS) 2013. 2014.
(6) United States AgencyInternational Development. Indonesia: Standard DHS, 2017. 2020; Available at: https://www.dhsprogram.com/ publications/publication-FR342-DHS-Final-Reports.cfm. Accessed June, 9, 2020.
(7) Fitria N, van Asselt ADI, Postma MJ. Cost-effectiveness of controlling gestational diabetes mellitus: a systematic review. Eur J Health Econ 2019 Apr;20(3):407-417.
(8) Eggleston K, Chen BK, Chen CH, Chen YI, Feenstra T, Iizuka T, et al. Are quality-adjusted medical prices declining for chronic disease? Evidence from diabetes care in four health systems. Eur J Health Econ 2020 Feb 20.
(9) Yamamoto JM, Kellett JE, Balsells M, García-Patterson A, Hadar E, Solà I, et al. Gestational Diabetes Mellitus and Diet: A Systematic Review and Meta-analysis of Randomized Controlled Trials Examining the Impact of Modified Dietary Interventions on Maternal Glucose Control and Neonatal Birth Weight. Diabetes Care 2018 Jul;41(7):1346-1361.
Chapter 6
130
(10) Zakiyah N, van Asselt ADI, Setiawan D, Cao Q, Roijmans F, Postma MJ. Cost-Effectiveness of Scaling Up Modern Family Planning Interventions in Low- and Middle-Income Countries: An Economic Modeling Analysis in Indonesia and Uganda. Appl Health Econ Health Policy 2019 Feb;17(1):65-76.
(11) Ministry of Health Republic of Indonesia. PMK No 97/2014. Pelayanan Kesehatan Masa Sebelum Hamil, Masa Hamil, Persalinan, dan Masa Sesudah Melahirkan, Penyelenggaraan Pelayanan Kontrasepsi, Serta Pelayanan Kesehatan Seksual. 2014.
(12) World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience: evidence base. 2016; Available at: http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1, 2018.
(13) Ministry of Health Republic of Indonesia and Japan International Cooperation Agency (JICA). Buku Kesehatan Ibu dan Anak. year 2016 ed. Jakarta: Ministry of Health of republic of Indonesia; 2016.
(14) Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) Study Group, Shankar AH, Jahari AB, Sebayang SK, Aditiawarman, Apriatni M, et al. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial. Lancet 2008 Jan 19;371(9608):215-227.
(15) Summit Institute of Development. The SUMMIT. 2020; Available at: https://sid-indonesia.org/. Accessed June,9, 2020.
(16) Taylor BL, Woodfall GE, Sheedy KE, O’Riley ML, Rainbow KA, Bramwell EL, et al. Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2017 May 5;9(5):10.3390/nu9050461.
(17) Peng TR, Wu TW, Chao YC. Effect of Probiotics on the Glucose Levels of Pregnant Women: A Meta-Analysis of Randomized Controlled Trials. Medicina (Kaunas) 2018 Nov 1;54(5):10.3390/medicina54050077.
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(18) Zhang J, Ma S, Wu S, Guo C, Long S, Tan H. Effects of Probiotic Supplement in Pregnant Women with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res 2019 Sep 5;2019:5364730.
(19) Kijmanawat A, Panburana P, Reutrakul S, Tangshewinsirikul C. Effects of probiotic supplements on insulin resistance in gestational diabetes mellitus: A double-blind randomized controlled trial. J Diabetes Investig 2019 Jan;10(1):163-170.
(20) Sukma. A, Toh. H, Nguyen. T.T.T, Fitria. N, Mimura. I, Kaneko. R, Arakawa. K, Morita. H. Microbiota community structure in traditional fermented milk dadiah in Indonesia: Insights from high-throughput 16S rRNA gene sequencing. Milk Science International 2017;71:1-3. (21) American Diabetes Association. 13. Management of Diabetes in
Pregnancy: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018 Jan;41(Suppl 1):S137-S143.
(22) Central Bureau of Statistics (BPS). Proportion of Population With Minimum Calorie Intake Below 1400 Kcal / Capita / Day by Province. 2020; Available at: https://www.bps.go.id/dynamictable/2018/06/05/1414/ proporsi-penduduk-dengan-asupan-kalori-minimum-di-bawah-1400-kkal-kapita-hari-menurut-provinsi-2015-2018.html. Accessed July, 2020.
(23) Ministry of Health Republic of Indonesia. Standar Tarif Pelayanan Kesehatan Dalam Penyelenggaraan Program Jaminan Kesehatan. 2016. (24) World Health Organization, Food and Agricultural Organization of
the United Nations. Vitamin and mineral requirements in human nutrition. 2nd ed. China: Publishing and Multimedia Service, Information Division, Food and Agriculture Organization of the United Nations; 2004.
