The effect of induced abortion on the risk of low birth weight

Transcription

1 Title The effect of induced abortion on the risk of low birth weight Author(s) Cui, Limin.; 崔 李 敏. Citation Issued Date 2012 URL Rights The author retains all proprietary rights, (such as patent rights) and the right to use in future works.

2 Abstracts of dissertation entitled The Effect of Induced Abortion on the Risk of Low Birth Weight Submitted by Cui Limin for the Degree of Master of Public Health at The University of Hong Kong in August 2012 Background: China accounts for a quarter of the total number of induced abortion worldwide. Induced abortion is considered as one of the risk factors for adverse pregnancy outcome in subsequent pregnancy. The effects of induced abortion on premature delivery were investigated in both China and western countries, and most of the studies showed that increased risk of preterm birth was associated with increasing number of induced abortion. However, the association between low birth weight (LBW) and multiple induced abortions is still controversial. Objectives: To explore the association between LBW and previous induced abortion history, and to investigate the effects of preterm birth on the association. Methods: This case-control study used data from the Neonatal Intensive Care Unit (NICU), Nan Fang Hospital, between December 2011 and June We recruited i

3 402 LBW (less than 2500 g) infants as our case group and 407 normal weight infants as the control group. Chi-square test and t-test were used for descriptive analysis. Multivariate logistic regression was run to yield odds ratios (OR) of LWB for multiple induced abortion adjusting for sex, birth order, maternal previous diseases and age, antenatal care received, and inter-pregnancy interval. Mediation effect of preterm status was investigated. Results: We observed a higher proportion of women with multiple induced abortions in LBW group (18.4% versus 11.1%, p value=0.003). Mothers with previous multiple induced abortion were 68.3% (95% confidence interval (CI): 11.0% to 155.3%) more likely to have LWB infants, compared with those who did not have induced abortion history or only once. After adjustment also for preterm status, the adjusted OR reduced to (95% CI: to 2.602) and the association became non-significant. Mediation test confirmed that preterm status was a mediator factor between multiple induced abortion and LBW. Conclusion: Overall, multiple abortions had an effect on LBW mainly through shortening the gestational duration of infants. Either premature delivery or LBW, the effect of multiple abortions on subsequent pregnancy was confirmed in this study. To reduce the perinatal mortality and morbidity, it is not enough only through postpartum care for preterm birth and LBW. The prevention and intervention strategies are urgently needed for reducing the induced abortion rate. Keywords: induced abortion, Low birth weight, preterm birth ii

4 The effect of induced abortion on the risk of low birth weight by Cui Limin A dissertation submitted for the Degree of Master of Public Health at The University of Hong Kong August 2012 iii

5 Declaration I declare that the dissertation and the research work there of represents my own work, except where due acknowledgement is made, and that it has not been previously included in a thesis, dissertation or report submitted to this University or to any other institution for a degree, diploma or other qualifications. Signed Cui Limin Cui Limin iv

6 Acknowledgements It is true that pursuing MPH study in HKU is a challenging undertaking; it is however, a myth to imagine it as a lonely expedition. My work in this dissertation could only have been completed with the helps and supports of many people. It is to them that I owe my deepest gratitude. First of all, I would like to express my sincere gratitude to my superior, Dr. Huang Weimin, Prof. of NICU Department of Nan Fang Hospital. Without his helps, I would never have the chance to begin and the courage to conquer this one year journey. Their never-ending encouragements and supports are greatly appreciated. I would like to express my sincere gratitude to my supervisor, Prof. TH Lam, and my statistical advisor, Dr. Tracy Lo. They are the true mentors, advisors and teachers during my journey towards a MPH dissertation. Their inspirations, supports and patience are greatly appreciated. It is also a great opportunity to respect all of teaching staff in School of Public Health, The University of Hong Kong for their teaching, advices and supports during my study. I am also grateful to all my classmates and friends for their kindness and support v

7 during my study in Hong Kong. In particular, to Miss Wang Li, Miss Li Dan, Miss Feng Sumin, and Miss Ma Lin for their supports and encouragements and the brainstorming with them. Our friendship will remain with me for ever. I owe a special thanks to all persons that have even given me helps and supports. Last but not the least, I d like to thank the understanding, motivation and support from my families to whom I indebted a lot in this year. vi

8 Contents Chapter 1 Introduction Background Literature review Worldwide situation Reasons for induced abortion around the world Situation in China Different types of induced abortion Consequence of induced abortion and multiple induced abortions Consequence of induced abortion Complications of induced abortion Low Birth Weight Risk factors Genetic factors Demographic and psychosocial factors Obstetric factors Smoking or environment tobacco smoke (ETS) exposure during pregnancy Prenatal care Consequences of LBW Preterm status...19 vii

9 4.1 Preterm related to mortality and morbidity Risk factors Genetic factor Previous preterm labor history Previous abortion history Preterm birth may have effect on the association between abortion and LBW.21 Chapter 2 Research gaps and objectives of this study...22 Chapter 3 Method Inclusion criteria Exclusion criteria Data collection Statistic analysis Descriptive statistics Univariate analysis Multivariate logistic regression analysis Mediation analysis Chapter 4 Result Chapter 5 Discussion Implicaitons Compared with previous studies Limitations Lack of important viii

10 information Inaccuracy in sample size calculation Data defect Suggestions for further research Sample size Data collection Public health Sex education for young people Contraception dissemination for unmarried women Policies implications...50 Chapter 6 Conclusion...54 Chapter 7 References...55 ix

11 List of Abbreviations LBW PB WHO EC PE MVA EVA D&C D&E ETS ELBW XPBs NICU low birth weight premature birth World Health Organization emergency contraception premature birth vacuum aspiration electric vacuum aspiration Dilation and curettage Dilation and evacuation environmental tobacco smoke extremely low birth weight extremely early preterm birth neonatal intensive care unit x

12 List of Tables Table 1 Characteristics of main variables in LBW and normal weight groups 30 Table 2 Odds ratio (OR) of Low Birth Weight according to the number of induced abortion for group Table 3 Odds ratio (OR) of Low Birth Weight according to the number of induced abortions in group 2.33 Table 4 Chi-square test between number of abortions and preterm status...34 Table 5 Odds ratio (OR) of LBW according to the number of induced abortions...35 Table 6 Odds ratio (OR) of preterm status according to the number of induced abortions...36 Table 7 Odds ratio (OR) of LBW according to preterm status.36 xi

13 Lists of Figures Fig 1 Disposition of all subjects (n=817) recruited in the study...25 Fig 2 Model for mediator test of the relationship between number of abortions and LBW by preterm birth xii

14 Chapter 1 Introduction 1. Background About 30 to 50 million induced abortions are performed annually around the world, as induced abortion is one of the most common methods to achieve birth control and terminate the unintended pregnancy(1). China almost accounts for a quarter of the total number of induced abortions globally. What is worse, a large proportion of induced abortions in China are multiple abortions(2). Induced abortion is considered as one of the risk factors for adverse pregnancy outcome in subsequent pregnancy. The effects of induced abortion on premature delivery were investigated both in China and in overseas countries, and the most consistant result showed that the increased risk of preterm birth was associated with increasing number of induced abortion. However, the relationship between low birth weight (LBW) and multiple induced abortions among previous studies is still controversial. LBW and preterm birth are closely related to perinatal mortality. Therefore, the aim of our study is to estimate whether multiple induced abortions can increase the risk of LBW. 2. Literature review 2.1 Worldwide situation Compared with 46 million induced abortions in 1995, there was a decrease in 2003, to 42 million. Though the overall data showed a downward trend, some developing countries like China and India presented little change or a rising trend, in other words, abortion rate mainly decreased in developed nations. Moreover, unsafe abortions 1

15 accounted for half of all abortions, and almost all the unsafe abortions were performed in developing countries(3). The World Health Organization (WHO) defined unsafe abortion as abortion procedure without a standard medical environment or/and a mature technology(4). Countries have different regulations or laws on induced abortion, some even regulate abortion as illegal, for example, in Peru and Philippines, induced abortion are strongly prohibited by law. As a result, unsafe abortions are more likely to happen in countries where induced abortion is restricted by law. Unsafe abortion would create around 70 thousand maternal death and 5 million disabilities per year globally(5). The maternal morbidity and mortality were related to illegal induced abortion in developing countries, as induced abortion was restricted in many developing countries(6). Furthermore, some articles suggested that clandestine abortion and abortions causing death are more likely to occur in young and unmarried women in developing nations.(7) Safe abortions are less available or affordable for patients in developing countries than developed countries due to different abortion laws among regions. In addition, women in developing countries may lack knowledge about correct contraceptives or lack access to modern contraceptive service, which result in the increase of unsafe abortion rate and further influence the rate of maternal death and disability Reasons for induce abortion around the world The majority of induced abortions are due to unintended pregnancies, which result from unprotected sex or contraceptive failure. On the other hand, induced abortion 2

16 can be regarded as an outcome, which is affected by several conditions, such as the affordability of a family to raise a child, the moral idea of local residents among different regions, the socioeconomic status, marital status, education level as well as the mental conditions of the pregnant women(8). In many countries, unmarried and younger women were more likely to have an abortion when their pregnancy was unintentional, because they had to work or go to school.(9) Thus, the different ideas on pregnancy and marriage could affect women s decision on whether to seek an induced abortion when unintended pregnancy happened. Studies carried out in Australia and Sweden presented that economic factors including household income and work status, were the most frequently reported reasons for induced abortion(10). Only one-tenth of women would suffer from the mental health problem like depression and anxiety after induced abortions, and this was the conclusion from a review in 1992(11). However, other articles (12) stated that women with previous mental diseases would have a higher risk to have difficulties after induced abortions compared with women without mental diseases. Further, pressure from the male partner - the male partner does not want a baby at the moment, could be another significant factor that related to women s negative emotion after induced abortion(13). To some extent, induced abortion can not only be attributed to accidental pregnancy, women s background and characteristics should be taken into consideration, because these demographic characteristics could have an impact on women s attitudes, understanding, and motivation on induced abortion.(9) 3

17 2.2 Situation in China The number of induced abortion in China has reached up to million in 2012, which almost accounts for a quarter of the total number of induced abortions globally. What is worse, a large proportion of induced abortions in China are multiple abortions (twice or more) (14). The high induced abortion rate among Chinese women may be associated with their sexual behavior. Confucianism, the backbone of Chinese culture, has influenced people for thousands of years. It not only involves a religion, more importantly, it has great impacts on an ethical or moral norm system. To be specific, in traditional concepts of Chinese culture, a girl who is pregnant before marriage would bring disgrace to the whole family and she would be considered to be shamed. Situation of pregnancy before marriage in China has changed a lot during different time periods. In the past, relationship between unmarried men and women was relatively conservative, premarital pregnancy was not common. However, since 1980s, with the development of Chinese economy, Chinese culture is widely influenced by Western. The relationship between unmarried men and women became less restriction than before. Besides, school and family planning organizations did not pay more attention on contraceptive education for young peoples. In this case, there came a sharp increasing rate of premarital sex, premarital pregnancy, as well as the induced abortion (14). Pervious study suggested that Chinese women had a low rate(15) of contraceptive use, especially among young women. And women had their first sexual intercourse younger than 20 years may have a high rate of non-contraceptive use, which increased 4

18 the risk of unwanted pregnancy. Education level is another important factor related to contraceptive use because women with low education level may lack of knowledge about contraceptive methods and the importance of contraceptive use(16). In China, there are a special population named migrant workers, who are people born in rural areas but work in prosperous cities. Unmarried, young women take up a substantial proportion of this population. According to the census in Beijing, 1997, around 45% of migrant women workers stayed in the city for more than half a year.(17) However, many of them know little about contraception and safe sex activities; low contraceptive use rate and high unprotect sexual behavior rate among them may lead to an increase in unintended pregnancy and induced abortion, as well as reproductive tract infections(18). Contraceptive failure is a very significant reason for unwanted pregnancies. One study carried out in Zheng Zhou suggested that approximate 72% of 1093 pregnant women could attribute to contraceptive failure(15). Emergency contraceptive (EC) is an effectiveness method to prevent unwanted pregnancy when contraceptive failure occurs, however, even women realize their contraceptive is failed, less of them would choose EC timely. This phenomenon can come down to the incomplete education system of sex education.(15) In addition, whether the usage of contraceptive method is correct and consistent is another element that affects the success of contraceptive. In China, condoms and contraceptive drugs are available as nonprescription products at pharmacies. Residents obtain contraceptive products usually without professional advice and guidance, only rely on introductions which are too simple and incomplete 5

19 for users to know how to use condoms and pills. Thus, users misunderstanding on introductions would influence the effective use of contraception. The advanced medical technologies such as sonography and amniocentesis can help doctors and parents know the baby sex before childbirth, but it also creates sex-selective abortion, especially in rural area in China. However, different from other Asia countries like South Korea where has a same tradition on preference for male child, China has the one-child policy, which may make the sex-selection abortion of female fetuses become more serious since The male to female sex ratio at birth had reached up to 1.22:1 until 1993(19). In consideration of the imbalance sex ratio which would create many social problems, the Chinese Ministry of Health proposed an urgent notice on strictly forbidding use of medical technology to perform prenatal sex determination in 1989(20), however, such behaviour can not be eliminated(19). Data provided by Demographic and Reproductive Health Survey of China suggested that until 1997, approximate 27 percent of rural women had experienced one or more abortion since they wanted a male baby.(21) The strictly implemented one-child policy is one of the most important factors for the increased induced abortion rate in China. Chinese government published the policy on 13 March, 1982, which advocated late marriages and late childbirth, fewer and healthier births. There are two channels to implement this policy: one is unmarried young people marry at a mature age; the other is married couples adopt scientific contraceptive methods to achieve birth control. Apart from the one-child policy, the 6

20 life stress makes young people tend to get married or give birth at a later age, especially in metropolis like Guangzhou, Shanghai, and Beijing. However, delayed marriage among young people does not mean delayed sexual activities. Unmarried females account for a high proportion among abortion women because of unplanned pregnancies usually caused by irregular sexual life and non-standard contraceptive measure use. Under the one-child policy, married women who already have one child and got pregnant unplanned would be forced to have an abortion. Moreover, the tradition of preferred male child combined with the medical technology that can help to distinguish the sex of fetus may make many women choose to have an abortion if they know they conceive a baby girl. 2.3 Different types of induced abortion WHO defined induced abortion as using artificial methods to remove an immature fetus or embryo from the uterus, and to achieve the purpose of terminating an unintended pregnancy. According to the gestation age, induced abortion can be divided into early abortion (gestation age less than 12 weeks) and medium induction (gestation age between 12 and 24 weeks). Medical and surgical methods are the most common methods to achieve the termination of pregnancy. Medical abortion is suitable for gestation age within 7 weeks, thus it is only appropriate for women with regular menstruation. Mifepristone (Ru 486) combined with prostaglandin becomes the most common and more effective treatment for terminating early pregnancy. Compared with surgical abortion, medical abortion can 7

21 avoid pain and complications such as perforation of uterus, uterine infection, which can be caused by operation. Currently, mifepristone misoprostol combination regimen is widely used around the world because it can achieve up to 98% effectivity to terminate pregnancy before 9 weeks gestation age.(22) However, there is 0.5% to 2% incidence of incomplete abortion, which is one of the most common complications of medical abortion. Women with incomplete abortion have to encounter further surgery. Surgical abortions include suction-aspiration or vacuum aspiration, dilation and curettage (D&C), dilation and evacuation (D&E). Vacuum aspiration can be used as a process of induced abortion in the first trimester, and as a further surgery when medical abortion has failed.(23) Vacuum aspiration is applied on the first-trimester (up to 12 weeks gestational age) abortions with or without cervical dilation. Due to the short time of less than 15 minutes for the vacuum aspiration procedure and the low cost, it is almost always processed outpatient. The only difference between manual vacuum aspiration (MVA) and electric vacuum aspiration (EVA) is the former uses a manual syringe and the later uses an electric pump, and they have the same level of suction thus they are equally effective and safe.(24) Dilation and curettage (D&C) is commonly used to diagnose or treat abnormal uterine bleeding, and also used for induced abortions due to incomplete miscarriage. D&C requires patients to undergo a general anesthesia, which would increase the risks of complications. Thus, D&C has been gradually replaced by safer and cheaper methods of medical abortion or non-invasive method, which was usually used for the 8

22 first-trimester abortion. World Health Organization suggested D&C could only be used as a kind of method for abortion when MVA is infeasible(25). Dilation and evacuation (D&E) could only be used for terminating the unwanted pregnancies when gestational age goes up to 12 weeks, which is defined as second-trimester. Abortions in second-trimester account for nearly 11% of the total number of induced abortions. There are two major steps in the procedure of D&E: first is to dilate the cervix, and second is to remove the fetus from the uterus. The whole operation process requires patients being under a local anesthetic or general anesthesia. During the D&E surgery, endometrial and cervical may be affected by different degrees of damages, such as uterine wall would turn into thinner after the surgery. Therefore, postoperative patients need a relative long time for recovery.(26) 2.4 Consequences of induced abortion and multiple induced abortions Consequences of induced abortion Abortion, especially surgical abortion, would cause various kinds of short-term complications and long-term sequelae on patients. Postabortal hemorrhage, intrauterine adhesion caused by infection, or uterine perforation because uterine wall damages during the operation(27) were the common typical short-term complications. Studies also suggested that induced abortion could increase the risk of low-birth-weight or preterm birth in the subsequent pregnancy(28). The incidence of complications after safe abortion shows a declined tendency, however, unsafe abortions that we mentioned above account for a large proportion of all induced 9

23 abortions, which seriously threatens women s reproductive health and life. Many young women regard induced abortion as conventional remedial measure, so they seek abortion frequently (twice or more), which is irresponsible for their health. Since women get pregnant, many systems of their bodies would be subtly changing to prepare for pregnancy. Nevertheless, terminating a pregnancy by having an abortion surgery would make the endocrine level of body drop dramatically without a gradual adaptive process, which would be a potential harm to the body. Multiple abortions (two or above) would increase the risk on organ function decline or premature aging. The different degrees of complications are related to women s age, gestational duration at induced abortion, technology they receive for the abortion, they have the abortion outpatient or inpatient, etc. Furthermore, vacuum aspiration is one of the most common methods of induced abortion, the speed, vigor, extent of cervical dilation, and the time of the procedure lasting would create minor and major complications.(29) Women having an abortion in different pregnancy trimesters also create various complications, for example, women undergoing the most common method such as vacuum aspiration or D&E during the first-trimester would have a lower complication rate compared with the second-trimester (30). According to previous studies, women at a young age, or lived in rural area, or abortion surgery were non-vacuum methods such as hysterotomy, D&C, presented higher risks for complications, and bleeding presented more seriously on women with induced abortion when their gestation age was more than 8 weeks (22). Moreover, women living alone or with low socioeconomic status were at a higher risk of 10

24 complications after two weeks of an abortion.(31) In many African countries, unsafe abortion is the first consideration for women with unwanted pregnancy because induced abortion is strictly restricted. Up to 30% of maternal deaths in these countries are related to clandestine abortion. Sepsis was the most significant side effect compared with other side effects caused by induced abortions(32). In addition to African countries, the case fatality rate presented by Ghanan, Barnes-Josiah et al. showed that septic abortion was three times higher than other induced abortion-related complications (33). Furthermore, women with prior induced abortions would increase the risk of ectopic pregnancy.(34) Ectopic pregnancy is a relatively dangerous disease that threats women s fertility and life. The embryo can not implant into women s uterus due to induced abortions leading to the womb trauma, thus the embryo would stay in other places instead of uterus. The more women have induced abortions, the higher the chance to develop ectopic pregnancy Complications of induced abortion We conclude the complications of induced abortion as three stages according to the timing of complication occur: 1) Intra-operative complications: Uterine bleeding (more than 200 ml) and uterine perforation are the most common complications during operation, in addition, some women may emerge many syndromes together including low blood pressure, 11

25 sweating, heartbeats accelerating during surgery, we call it abortion syndrome (35). 2) Postoperative complications: Sometimes incomplete induced abortions are caused by leakage suck or failed to suck embryonic organization out, so women have to undergo a further surgical because the pregnancy is still developing. Postoperative vaginal bleeding for 15 days or more is another common complication after surgery; pathogenic bacteria infection can cause endometritis, annex inflammation, pelvic inflammatory and intrauterine adhesions, which would become the risk factors of adverse outcomes in the following pregnancy if complete response does not present. 3) Subsequence pregnancy complications: women who have experienced multiple induced abortions will have a higher rate in spontaneous abortion during late period. Some women will suffer from infertility after repeated induced abortions. Adverse pregnancy outcomes like preterm, perinatal death of fetus or prenatal and/or postpartum hemorrhage of gravida will also be higher in women with multiple induced abortions. 3. Low Birth Weight Low birth weight (LBW) is considered as the main element related to the mortality and morbidity of infants(36). Nearly two-third of all neonatal deaths can be attributed to LBW(37). According to data provided by World Health Organization, babies born less than 2,500 g in 1982 took up approximately 16% (20 million) of all

26 million infants, and more than 90% of the LBW infants were born in developing countries.(36) The World Health Organization defined LBW as child's birth weight less than 2,500g, despite the gestational duration. Preterm birth (a short gestation period, less than 37 complete weeks of gestation) and small for gestational duration (retarded intrauterine growth) are the main reasons that cause LBW. Furthermore, mother's life habit such as smoking or drinking, malnutrition during pregnancy would also increase the risk of babies with LBW. Three terms are divided by different gestational age of LBW infants: 1) Preterm low birth weight infants (born before 37 complete weeks of gestation) 2) Term LBW babies (gestational age between 37 and 42 complete weeks) 3) Post-term LBW fetus (born after 42 weeks) Infants' birth weight between 1000 and 1499g is defined as "very low birth weight" and birth weight between 500 and 999g was called "extremely low birth weight", which also belongs to the LBW. LBW is not only a threat on the development of infant period, but also a risk factor that affects the life quality in the adulthood stage. Neuron-developmental problems are closely associated with LBW. Babies born with Low birth weight would have a higher risk in getting respiratory tract infections in babyhood, and learning disorders, behavior problems would occur when they grow up. Babies born with low weight may need more frequent hospital visits than normal birth weight babies. No doubt, this will increase the financial and emotional burdens for their families. 13

27 3.1 Risk factors: LBW as an adverse outcome of pregnancy, is associated with many factors, such as maternal nutrition, prior LBW history, smoking or drinking during pregnancy, antenatal care. The major risk factors of LBW are differed from women under different socioeconomic status, racial, etc Genetic factors -Sex of infants Baby s sex is not linked with any other factors, thus its association with gestational age and intrauterine growth restriction should be unconfounded, and the measurement on sex can be without any subject bias. Most of the previous studies presented there was no significant difference between male and female babies on the birth weight. Only few studies showed a significant association between sex and birth weight(38, 39) -Racial/ethnic origin In order to detect whether the birth weight varies in different population groups, racial/ethnic origin is necessary to be investigated. Cause people live in different countries or regions would have different body shape like height and weight, and the socioeconomic status is also different among different population groups, such as education, family income, jobs, and lifestyle such as calorie intake, vitamin consumption as well. Through relevant studies that compared Canada with Europe, France with North African, and Blank with Whites in U.S, it was demonstrated a 14

28 slight connection on premature with population groups.(38, 40, 41). Research carried out by Yudkin et al.(42) in Israel presented a difference in birth weight between women in North African countries and Western Israeli, or Asian countries. In Singapore, the mean birth weight of infants who delivered by Indian women would be lower than those delivered by Chinese or Malaysian mothers.(43) Demographic and psychosocial factors -Maternal age It can take up two years from menarche for a girl s body to develop a regular menstrual cycle; therefore, compared with adult, girls during this period would have a lower weight-for-height. Besides, women older than 35 reveal damaged intrauterine growth or gestational duration.(36) Thus, maternal age could be considered as a risk factor that is related to LBW or premature. However, neither studies carried out in developing countries(44) nor developed countries(45) showed a significant association between maternal age and birth weight. In contrast, women aged older than 35 presented higher rates in LBW and prematurity during their first and second trimester.(38) Young age may not be a direct factor which affects birth weight through linking with body development, nutrition, drinking and smoking, etc. -Socioeconomic status Socioeconomic status we mentioned above contains education level, working condition, and family income. Minority women in developed nations are more likely low in socioeconomic status 15

29 and antenatal care utilization, and high in smoking rate and genital tract infection. In addition, women with low socioeconomic status in developing countries may lack nutrition during pregnancy. -Marital status Marital status is closely connected with socioeconomic status. Single women, for example, unmarried teenagers or women whose male partner are absent during gestation period, would present a higher risk in having a low birth weight babies(46-48). -Psychological distress during pregnancy Previous studies suggested a positive association between major life events and premature delivery.(49) Emotional change, like stressful, anxious, will bring metabolic disorders that are related to appetite of pregnant women, further reduce the absorption of nutrition, thus, the development of fetus in uterine will be affected. Moreover, premature delivery could be produced by imbalance of hormonal or catecholamine caused by anxiety-mediated Obstetric factors -Birth or pregnancy interval Inadequate inter-pregnancy interval cannot let physical return to a normal level, which may lead to an adverse pregnancy outcome in subsequence. Study conducted among Blacks and Whites in the USA suggested that inter-pregnancy interval less than six month would increase the risk in LBW in the following pregnancy(50). -Prior induced abortion 16

30 Induced abortion procedure leads to different degrees of cervical dilation and/or uterine trauma; furthermore, multiple induced abortions would exacerbate endometrial damage on women and then increase the risk of preterm birth and LBW outcomes Smoking or environmental tobacco smoke (ETS) exposure during pregnancy Cigarette smoking during pregnancy may cause intrauterine growth restriction of fetal (36, 51, 52), and shorten the duration of pregnancy which leads to premature delivery(53), and finally elevate the neonatal mortality and morbidity rate. Even EST is not an active maternal behavior; women exposed in passive smoking would inhale the same amount of toxins compared with smokers. This will further influence the fetus development in uterine, which have a close relationship with the high risk of LBW(54). The Millennium Survey carried out in UK among 18,819 babies suggested that from 2002 to 2010, approximately 13% of all the babies exposed to ETS when they were in their mothers belly and almost 40% infants experienced maternal smoking. The birth weight of infants with ETS exposure and maternal smoking were significant lower than babies without(55). Other studies showed that women who experienced ETS exposure during pregnancy would increase the risk of LBW into 1.5 to four times compared with women had no history in EST exposure. In addition, maternal smoking was considered as a factor causing LBW through an influence on intrauterine growth restriction(56) Prenatal care Lack prenatal care usually happened on women with low socioeconomic status, 17

31 because of economic factors, poor women tend to give up seeking antenatal service or inconsistently use such care. Previous studies showed women undergoing prenatal care had a lower risk on the incidence of low birth weight babies delivery than women who did not. Moreover, low birth weight babies would have a better perinatal survival rate and were less likely to get respiratory distress or cerebral diseases if their mother had a regular prenatal care attendance rate(57). Many low birth weight infants are premature birth, a well pregnancy management is useful for detecting the reasons for LBW in an early period. Further, to achieve an early identification and/or intervention(58). 3.2 Consequences of LBW LBW is the major factor for the mortality and later morbidity of infants. Infections and nutritional diseases account for 10% neonatal deaths in the first day after birth. In most developed countries, infants who die during the first month after birth take up three-fourth of the mortality in the first year(59). Many of the surviving LBW babies, especially very low birth weight, will suffer from a lifetime serious health conditions, such as the cerebral palsy, blindness, hearing problems and learning disabilities(60). Children born with very LBW would have 25 times as high as normal weight children to get cerebral palsy(61). The survival rate can be improved through neonatal intensive care, however, the high incidence of neurodevelopment disorders becomes the major threat that affects the life quality of adulthood and childhood of infants who are born with LBW. 18

32 Previous study investigating children who were born with ELBW (extremely low birth weight) in the 1990s in USA suggested that ELBW significant increased the risk on chronic conditions. Apart from cerebral disease or respiratory system disease that occur in babyhood, cognitive disability and social adaptive dysfunction would along with the development of the childhood and adulthood(62). Other than disease burden LBW cause, it will take 1 million to save each infant whose birth weight is between 500 to 600 g(63), and the cost is only for survival. Upbringing payment and later treatment fees become a heavy financial burden for most families with LBW babies. Overall, LBW is a significant factor closely related to fetal mortality and morbidity. From public health prospective, the heavy disease and financial burden caused by LBW will bring many negative effects on health systems and human beings. Therefore, urgent actions should be taken to deal with this important public health problem. 4. Preterm status The definition of preterm birth is the gestational duration of baby at birth between complete 28 and 37 weeks. Gestational age less than complete 28 weeks, we call it extremely early preterm birth (XPBs). Premature labor has been considered as a major reason for neonatal mortality and long-term morbidity. As one of the vital factor was related to LBW, almost 70% LBW babies were born before 37 gestation weeks(64). 4.1 Preterm related to mortality and morbidity 19

33 It was reported that both mild (gestational age between 34 and 36 weeks) and moderate (baby was born at 32 to 33 gestation weeks) preterm labor had a relative high relative risk (RR) for postneonatal death because of infection(64). Other article showed that preterm LBW babies accounted for 30% of infants mortality(65). 4.2 Risk factors Premature delivery is related to mother s physiology factors: women with low socioeconomic status tend to have a higher risk on preterm labor Genetic factor: According to previous epidemiologic studies, the rate of preterm birth was more likely to occur on Black people, and women with the history of preterm birth often had family or race tendency(66). The recent study reported that premature delivery was a polygenetic diseases, which was controlled by multiple genes and vulnerable to environmental factors(67) Previous preterm labor history: The risks on preterm birth of women with preterm history were 3 times higher than women with term birth experience. And one-third of women with two consecutive preterm delivery history would reoccur the third time preterm labor(68) Previous abortion history: It was reported that abortion history was one of the important risk factors for placental presentation(69); abortion could cause damage on the lining of the womb, which affected the ability of embryos to attach to the uterus, so the position of the placenta 20

34 would stretch to the lower uterine segment, then lead to abortion. -Unhealthy living habits: Jaakkola et al,(70) suggested that women smoking during pregnancy would had 1.2 times higher risk on preterm birth than women did not smoke. Almario et al, reported that there were 3 times more risk of premature birth for women who drank during pregnancy(71). Socio-psychological factors were also suggested to be associated with premature delivery. Preterm birth was more likely to occur on women with a low socioeconomic status(72), which was due to the higher family income or education level women had, the more attention they would pay on prenatal care. The pressure of women during pregnancy would cause disorders of immune system and endocrine system, thus increase the risk of preterm birth(73). 4.3 Preterm birth may have effect on the association between abortion and LBW: Preterm birth is one of the most significant reasons related to LBW. Recently, preterm LBW birth rate has increase to 9% in China(74). Many researches had confirmed that women with previous termination of pregnancy would significantly increase the risk of premature birth. Lumely J studied the relationship between the abortion history and premature birth in both 1993(75) and 1998(76). The 1993 study reported that the prevalence of preterm birth among women with prior induced abortion was much higher than those who were first pregnancies. Moreover, there were above 5 times risk in preterm birth for women who 21

35 had three or more times of induced abortions. Lumley confirmed the dose-response relationship between abortion history and the prevalence of preterm delivery in And this showed a new result that the risk of extremely early preterm birth (XPBs) (infant born with less than 28 week gestation) of women who experienced four or more previous induced abortions would as nine times as high as primigravidas. A study conducted in Bavaria supported previous research, and reported that the Odds ratios (OR) for early preterm births (gestational age less than 32 weeks) with history of previous termination of pregnancy were higher than OR for preterm birth, regardless how many times induced abortion women had(77). In conclusion, surgical abortion including dilation and curettage, or dilation and evacuation is commonly used in clinical process, which can inevitable create cervical impairment or/and endometrial damage, thus increase the risk on adverse pregnancy outcome, and affect the fertility of women. Chapter 2 Research gaps and objectives of this study It was reported by Weijin Zhou et al(28), women with 2 or more induced abortions were significantly associated with LBW, but the result did not adjust for potential confounders. Brown et al.(59) confirmed this result in 2007, that women with prior induced abortion had an significant higher risk not only in LBW but also in preterm birth, compared with women without induced abortion history, and along with the increasing number of induced abortions, the risk on LBW and premature will increase. Earlier studies showed that multiple induced abortions could increase the risk of 22

36 giving birth to a very low birth weight baby up to three-folds(78). However, research conducted in Washington State showed an opposite result that the association between the number of induced abortions and LBW was non-significant(79). We did not find any direct study on the relationship between LBW and the number of induced abortion histories in Chinese-language literature. One of the indirect systematic review suggested that medical abortions showed a significant lower rate in the complications compared with surgical abortions in subsequent pregnancies, but there was no significant difference on preterm birth or LBW in both medical abortion and surgical abortion(80). Another study which investigated the risk factors of LBW suggested that women with induced abortion history combined with other factors such as maternal age older than 35 years old, smoking during pregnancy, BMI above 28 before pregnancy, would have a positive association with preterm LBW. In addition, women living in rural area, maternal light weight before pregnancy and women with induced abortion history would significantly increase the risk of term LBW(81). As described in the above sections, there is limited knowledge about the association of multiple induced abortion and LWB available in China. Even fewer studies have investigated the effect of preterm birth on this association. Thus, in this study, we aimed to: 1) investigate the association between multiple induced abortion history and LBW in Chinese population; 2) compare the difference on the risk of LBW between women with different times of induced abortion and women without induced abortion; 3) explore the effect of preterm birth on the association between multiple induced 23

37 abortion and LBW. Chapter 3 Method This is a case-control study. Two experienced registered nurses helped collect the data in the NICU department, Nan Fang hospital, Guangzhou during December 2011 to June During the data collection period, 817 infants were admitted into the hospital, while 809 of them were recruited in our study based on the following inclusion and exclusion criteria: 3.1 Inclusion criteria: 1) Live-born singleton infants who have completed weeks gestational age. We restricted the gestational duration between 34 and 41 weeks due to infants born with a gestational age less than 34 weeks were more likely to have a lower birth weight. In order to avoid bias caused by gestational duration on birth weight, babies born before 34 gestation weeks would be excluded from this study. The inter-pregnancy interval of their mother had to be more than 6 months for the reason that maternal physical function needed at least 6 months to return to a normal level(28). 3.2 Exclusion criteria: 1) Medical abortion and spontaneous abortion The purpose of this study is to investigate induced abortion that may cause 24

38 cervical dilation and/or uterine trauma due to artificial factors. In contrast, medical abortion is a high effective and safe procedure that may not need further cervical dilation or uterine curettage. 2) Infant birth weight less than 450g or greater than 7000g (n=2) 3) Gestational age at birth above 41 weeks or before 34 weeks (n=2) 4) Twins or multiple births (n=2) Twins or multiple births have a high rate in low birth weight and premature. 5) Mothers' inter-pregnancy interval less than 6 months (n=1) 6) Maternal age older than 45 or younger than 18years old (n=1) Figure 1 Disposition of all subjects (n=817) recruited in the study LBW infants:408 Normal weight infants:409 Birth weight less than 450g: 2 Gestational age at birth before 34 weeks: 1 Gestational age at birth after 41 weeks: 1 Twins: 2 Maternal inter-pregnancy interval less than 6 months: 1 Preterm: 341 Full-term: 61 Maternal age older than 45 or younger than 18 years old: 1 Preterm: 26 Preterm: Data collection: This study was approved by the Ethics Committee of Nan Fang Hospital. Finally, eight babies were excluded from this study. We had 402 LBW babies in case group and 407 normal weight babies in control group. The following information was 25

39 collected mainly based on computerized history record of babies in NICU and maternal conditions in obstetrics: 1) Birth weight and LBW: Birth weight less than 2500 g was defined as LBW 2) Induced abortion: Women with one or without induced abortion Women with multiple induced abortions (two or more) 3) Preterm status: gestational age before 37 completed weeks was defined as preterm birth 4) Demographic factors: Sex Birth order of infant Maternal age (35 years old or younger, more than 35) Marital status (married, unmarried) Antenatal care during pregnancy (no, irregular, regular) Inter-pregnancy interval with last induced abortion Maternal previous diseases As socioeconomic status of the family was not recorded in the computerized history records, this factor was not included in this study. Sample size calculation and power: Based on a study conducted in the United States(79), to achieve 80% power and 5% type 1 error, with the proportion of LBW in women with none or one induced 26

40 abortion was 0.05, in women with two or more induced abortion was 0.08, the sample size needed was As we have included 809 subjects in our study (50.3% were control), we calculated that the power of our study was Statistic analysis: We used SPSS 13.0 for the data analysis, and used Stata for sample size and power calculation. Our statistic analysis under the significant level is Descriptive statistics: Distributions of all factors, number (%) for categorical variables and mean (standard deviation, SD) for continuous variables 3.6 Univariate analysis: Chi-square test for categorical variables: (sex of infants, antenatal care during pregnancy, number of induced abortions) T-test for continuous variables (gestational age of infants at birth, birth weight of infants, maternal age) Binary logistic regression was used to calculate odds ratios and 95% confidence intervals (CI) between abortion and LWB 3.7 Multivariate logistic regression analysis: 27

41 Potential confounders including sex, birth order of infants, maternal age and previous disease, antenatal care during pregnancy, inter-pregnancy interval after last abortion were analyzed by multivariate logistic regression. The first was the crude model between number of induced abortions and LBW, without adjusting any factors. The second was LBW regression on number of induced abortion with adjusted for all confounders including sex, birth order of infants, maternal age and previous disease, antenatal care during pregnancy, inter-pregnancy interval, except preterm status. The third was the second regression model and added preterm status into adjustment. The fourth was preterm status regression on the number of induced abortions with adjustment except LBW. The fifth was the LBW regression on preterm status, adjusted for all variables except for the number of induced abortions. According to the literature review, we did not find the effect of preterm birth on the association between abortion history and LBW, so we hypothesized that preterm birth as a mediator factor. Therefore, there would be three causal pathways for number of abortion effect on LBW: 1. Abortion causes LBW directly, without causing preterm 2. Abortion causes preterm, which leads to LBW, but abortion does not cause LBW. 3. Abortion has a direct effect on LBW, and also an indirect effect through preterm. 28