Preterm Birth And Abortion PowerPoint Presentation

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PRETERM BIRTH AND ABORTION Mary L Davenport, MD, FACOG Magnificat Maternal Health Program July 31-August 3, 2013 Medical Women’s International Association Seoul, Korea © 2013

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Disclosure There are no commercial products mentioned in this lecture nor is support being supplied by any vendor, agency, or governmental grant or agent.

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Preterm Birth and Abortion Introduction Frequency of preterm birth Risk factors Biological pathways Studies on preterm birth and abortion Meta-analyses Recent studies Medical vs surgical abortion Conclusion

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Preterm Birth: World-wide 15,000,000 preterm births annually world-wide; one in 10 world-wide Leading cause of newborn death Second cause of death (after pneumonia) of children under 5 Fourth Millennium Goal: reducing mortality rate in children under 5 by two thirds between 1990 and 2015; preterm birth is a big factor Assessing gestational age in low-resource settings difficult; low birth weight used as proxy Back S et al. Bull World Health Organ, 2010

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Preterm Birth: under 37 weeks Extremely preterm < 28 weeks Very preterm 28-32 weeks Moderate to late preterm 32 to <37 weeks

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60% of preterm births occur in Sub-Saharan Africa and Southern Asia Nour N. “Preterm delivery and the MDG.” Rev Obstet Gynecol, 2012.

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South Africa More than eight out of ten births are preterm – less than 37 weeks. WHO 2012, The Global Action Report on Preterm Birth

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Preterm Birth: High vs Low Income Nations High income nations 50% of 24 week babies survive 90% of <28 week babies survive Low resource nations 50 % survival does not occur until 32 weeks 90% of <28 babies die within a few days Nour N. “Preterm delivery and the MDG.” Rev Obstet Gynecol, 2012.

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In the USA we have come a long way…. Patrick Bouvier Kennedy August 7-9, 1963 Born by cesarean section at 34 ½ weeks gestation 2.11 Kg (4 lb10 ½ oz) Died of hyaline membrane disease Accelerated research in surfactant, CPAP, respiratory therapies 2013: Survival nearly 100% at 32 weeks gestation

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Preterm Birth: USA 210,000 births annually 12% of all births are preterm 2% are Very Preterm Births (<32 weeks) Leading cause of neonatal death At risk for lifelong respiratory, visual, cognitive complications Preterm birth has risen 20 % in past two decades Estimated annual cost $26 Billion Average cost $51,600 per infant March of Dimes, Peristats. Hamilton B et al. CDC Vital Statistics Reports, 2012. Behrman,E et al. Preterm Birth: Consequence, Causes and Prevention. 2007

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Kangaroo Care

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Morbidity of Preterm Birth Very low-birth (VLBW) weight costs 28 times (RR) term ($280,146 versus $9,803)1,2,3 Low-birth weight costs 4 times (RR) term ($38,367 versus $9,393)1,2,3 Cerebral palsy increases by 147 times in VLBW compared to term (> 37 weeks)4 1Petrou S, Mehta Z, Hockley C, Cook-Mozaffari P, Henderson J, Goldacre M. Pediatrics 2003;112(6):1290-1297 2Luke B, Bigger H, Leurgas S, Siesma D. The cost of prematurity: a case-control study of twins vs. singeltons. AM J Publ Health. 1996;86(6):809-814. 3Infant Health in America:Everybody’s Business. Hartford, CT:CIGNA Corp 2000 4Himpens E, Master PT, Van den Broeck C, Oostra A, Calders P, Vanhaesebrouck P. Prevalence, type, distribution of cerebral palsy in relation to gestational age: a meta-analysis review. Develop Med & Child Neuro 2008;50:334-340.

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Long-term impact of Preterm Birth on Survivors Nour N. “Preterm delivery and the MDG.” Rev Obstet Gynecol, 2012

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Risk factors for preterm birth Previous preterm delivery Uterine distension Cervical trauma Infection Placental issues Abdominal surgery during pregnancy Fetal anomaly Chronic diseases Demographic: maternal age (< 18 or > 40 ), black race, genotype Low interconceptional interval Social: nutrition, smoking, substance abuse Psychosocial: anxiety, depression, stress Occupational: physical exertion, standingnet Genetic Abortion??? Robinson J et al. “Risk factors for preterm birth,” UptoDate. 2012

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WHO: “Born Too Soon”, 2012 WHO “The Global Action Report on Preterm Birth report on PTB” in 2012 No mention of abortion as a risk factor on page 20 of report. In fact, no mention of abortion at all as a PTB risk factor in the world or as an explanation for rising PTB rates WHO 2012, “The Global Action Report on Preterm Birth”, p 20.

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Preterm labor: biological pathways QUIESENCE Progesterone, prostacyclin (PGI2), nitric oxide, relaxin, and parathyroid hormone-related peptide contractions These substances increase cAMP Inhibit release of calcium from intracellular stores Inhibit MLKC ACTIVATION Increased levels of CAP’s (contraction-associated proteins); cytokines; Activated by myometrial stretch Leads to activation of CRH (corticotropin-releasing hormone) and withdrawal of progesterone Increased levels of prostaglandins Behrman,E et al. Preterm Birth: Consequence, Causes and Prevention. National Academies Press, 2007

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Biological pathways to preterm birth: Inflammation Gene-environment interactions may be responsible for pathology; genetic polymorphisms may play a role in inducing a harmful inflammatory response Caucasians: Factor V Leiden (FVL) was significantly associated with PTB (OR 2.6, 95% CI 1.31-5.17) African-Americans: significant associations with polymorphisms in the maternal interleukin IL-12 gene and the fetal IL-2RB receptor Holst D et al. Eur J Obstet Gynecol Reprod Biol. 2008 Velez DR et al. PLoS One. 2008 Velez DR et al. Am J Obstet Gynecol. 2009.

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ACOG, WHO and the medical community have disregarded the link between abortion and preterm birth. 135 studies* have demonstrated an association between abortion and preterm birth No studies show lower rate of preterm birth after abortion Studies from diverse locations world-wide Most pronounced association with very preterm birth and multiple abortion Some ethnic groups are disproportionately impacted: Africans and African Americans *as of February,2013

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Meta-analysis by Shah, et al 2009 Screened 834 papers Excluded 765 for lack of data and objectivity; retrieved 69 citations 37 included studies 18 studies with Low Birth Weight (LBW) 22 studies for preterm birth (PTB) 3 studies for small for gestational age (SGA)

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Meta-analysis by Shah, et al 2009 18 LBW Studies No abortions vs induced abortions No abortion vs 1 IAB 18 studies 280,529 patients OR 1.35 [1.20-1.52] No abortions vs > 1 IAB 5 studies of 18 49,347 patients OR 1.72 [1.45-2.04]

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Meta-analysis by Shah, et al 2009 22 PTB Studies No abortions vs induced abortions No abortion vs 1 IAB 22 studies 268,379 patients OR 1.36 [1.24-1.50] No abortions vs > 1 IAB 7 studies of 22 158,421 patients 1.93 [1.38-2.71]

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Meta-analysis by Swingle, et al 2009 Meta-analyses of literature 1995-2007 Pro-abortion and pro-life authors 7,891 titles, 349 abstracts, 130 papers 30 abortion and 26 SAB papers included Analyzed data from 12 induced and 9 SAB papers

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Meta-analysis by Swingle, et al 2009 12 studies used to calculate common OR’s for induced abortion 1 induced abortion 1.25 OR [1.03-1.48] increased risk preterm birth < 37 weeks > 1 induced abortion 1.51 OR [1.21-1.75] increased risk preterm birth < 37 weeks

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Meta-analysis by Swingle, et al 2009 4 studies available for common OR’s for induced abortion < 32 weeks (very preterm birth) Common OR 1.64 [1.38-1.91] Increased very preterm delivery rate of 64% Similar to other literature’s findings

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Two studies from 2012 Watson, et al: very preterm births (20- 31⁶ weeks) Case control study from Australia; 603 cases and 796 controls from 2002-2004 Findings: Terminations 1 abortion OR 2.11 (1.3,3.4) p<0.002; AOR 2.02 (1.2,3.3) p<0.004 > 1 abortion OR 4.4 (1.9,9.1) p<0.001; AOR 3.50 (1.6,7.9) p<0.002 SAB’s 1 SAB OR 2.06(1.4,3.1) p<0.001; AOR 2.03(1.4,3.1) p<0.001 > 1 SAB OR 3.01(1.8,5.0) p<0.001; AOR 2.82(1.7,4.8) p<0.001 Watson LF, Rayner JA, Forster D.. Midwifery 2012

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Two studies from 2012 Watson, et al: Conclusions Two groups of risks Lifestyle factors – being single, separated or divorced, smoking and drug use, as well as a history of pregnancy termination Pre-existing medical conditions–prior preterm birth, a history of miscarriage, bleeding in prior pregnancies, and diabetes “Our aim is that by presenting the findings summarised together, the data may be helpful for those providing care to women antenatally, particularly when taking medical histories in early pregnancy or in pre-pregnancy clinics.” i.e. Elective abortion is HIGH RISK factor for PTB and need to be AWARE as physicians and patients!

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Two studies from 2012 Klemetti, et al: preterm birth Nationwide register-based outcomes of first births in Finland; records linked to outcomes 1996-2008; 300,858 first time mothers Controlled for comorbidities: maternal age, marital status, socioeconomic position, urbanity, smoking, reproductive history; method, timing and indication of abortion Increased odds for very preterm birth (<28 weeks)seen in all the subgroups exhibited a dose–response relationship: One IA 1.19, two IA’s 1.69; three IA’s 2.78 Increased odds for preterm birth (<37 weeks) and low birth weight (<2500 g and <1500 g) were seen among mothers with three or more IAs: 1.35 (1.07–1.71) < 37 weeks , 1.43 (1.12–1.84) < 2,500 g, 2.25 (1.43–3.52) < 1,500 Klemetti R, et al. Human Reproduction, 2012.

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Two studies from 2012 Klemetti, et al: preterm birth Conclusions: “In terms of public health and practical implications, health education should contain information of the potential health hazards of repeat IAs, including very preterm birth and low birth weight in subsequent pregnancies.” “Health care professionals should be informed about the potential risks of repeat IAs on infant outcomes in subsequent pregnancy.”

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Two studies from 2012 Klemetti, et al: preterm birth Final Thought by researchers: “Observational studies like ours, however large and well-controlled, will not prove causality.” Same thing said by tobacco research.

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Bradford Hill Criteria Developed to draw causal inference from epidemiological association In 1964, the US Surgeon General applied the newly developed Bradford Hill criteria for causality to the cigarette lung cancer link epidemiologic studies to warn the public Tobacco-lung cancer link known since the 1940’s A response to politicized “tobacco science”

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Criteria for drawing a causal inference from epidemiological association: abortion and preterm birth fulfill many criteria Timing: abortion occurs before preterm birth Dose effect: risk is higher with more exposure Consistency of effect: demonstrated in many populations Strength of association: more association with very preterm birth Biological plausibility: abortion leads to chronic inflammation and cervical incompetence

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More medical abortions: An important trend 44,000,000 abortions world-wide in 2008 Medical abortion – mifepristone and misoprostol or misoprostol alone - is increasing as a proportion of all abortions internationally – legal and clandestine USA: 17% of all nonhospital abortions, 25% of abortions < 9 weeks in 2008 European countries: medical abortions as percentage of abortions: Scotland 2012 77%, Sweden 2011 75%, Denmark 2011 56%, Finland 2011 89% International perspectives on global and reproducitve health; Vol 38, no 1. March 2012

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Changes in association of abortion and preterm birth: Scotland 1980-2008 Historical cohort study of 732,719 first births >24 weeks Preterm delivery <37 weeks declined over time Surgical without use of cervical pre-treatment decreased from 31% to 0.4%; medical abortions increased from 18% to 68% during this period Previous abortion associated with preterm birth most prevalent 1980-1983 (OR 1.32 [1.21–1.43]) ; overall OR (1.12 [1.09–1.16]) Oliver-Williams C et al. PLoS Medicine, 2013

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Changes in association of abortion and preterm birth: Scotland 1980-2008 Oliver-Williams C et al. PLoS Medicine, 2013

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Changes in association of abortion and preterm birth: Scotland 1980-2008 Headlines – “Modern methods of abortion not associated with preterm births.” “Maternal abortion no longer associated with preterm birth.” Authors: “We speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth.” Is this really true? Other studies show no difference in PTB between medical and surgical abortion.

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Oliver-Williams C et al. PLoS Medicine, 2013

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Medical and surgical abortion: China 1998-2001 Compared birth outcomes in women with one prior medical or surgical abortion vs no abortions 4,925 women with no history of induced abortion 4,931 women with one mifepristone-induced abortion 4,800 women with one previous surgical abortion Lost to follow up <1% No significant differences comparing medical and surgical abortion in risk of preterm delivery (28-37 weeks), frequency of low birth weight Chen A et al. Am. J. Epidemiol. 2004

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Medical vs surgical abortion: Finland 2000-2009 All primigravid women with one prior induced abortion and singleton delivery Population-based register study Medical (n = 3441) or surgical (n = 4853) abortion; total 8294 No statistically significant difference in risk of preterm birth with medical vs surgical abortion 4.0% risk with medical abortion 4.9% risk surgical abortion Mannisto J et al. BJOG. 2013

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Mifepristone and misoprostol are highly pro-inflammatory

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Medical abortion: high failure rate Studied all Finnish women undergoing abortion < 9 weeks gestation 2000-2006 42,619 abortions: medical 22,368 and surgical 20,251 Adverse events four times higher with medical abortions; 20% vs 5.6% Rate of hemorrhage 15.6% Surgical (re)evacuation 5.9% of medical abortions; 1.9% of surgical abortions (P<.001) Niinnimaki, M. et al. Obstet Gynecol. 2009.

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China: Repeated medical abortions and the risk of preterm birth in the subsequent pregnancy Cohort study of 7 hospitals in Chendu 2006-2009 Delivery outcomes known in 18,323 1 surgical abortion 40% increase PTB 3 or more surgical abortions 62% increase in PTB Combined medical surgical abortion increase of 212% (20% of medical IAB had surgical evacuation) 69% increase in PTB with surgical evacuation < 7 weeks 360% increase in PTB with med-surg abortion < 7 weeks Liao H et al. Arch Gynecol Obstet . 2011.

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Israel: Clinical, surgical and histopathologic outcomes following failed medical abortion Medical-surgical abortions are associated with significant necrosis and inflammation 104 surgical abortions vs 104 medical-surgical abortions Inflammation quantified by immunohistochemical stains for T and B lymphocytes and macrophages; necrosis evaluated morphologically Abnormal findings more frequent in the med-surg group; 10.9% vs 1.9% Most frequent abnormality in the case group was the presence of intimately adherent products of conception, necessitating sharp curettage “The long term consequences of curettage following failed medical abortion warrant further investigation.” Fuchs N et al. Int J Gynaecol Obstet. 2012

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Conclusions Induced abortion increases preterm birth rates substantially in latest large studies and meta analyses; 135 studies now with statistical significance (February, 2013) Medical abortion does NOT eliminate risk of preterm birth Preterm birth increases risk for cognitive, visual and other deficits substantially; cerebral palsy by 147 times Health care-neonatal costs increased by billions Patients, governments and health care organizations need to know consequences and costs related to induced abortion

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With thanks to Byron C. Calhoun, MD, FACOG, FACS, MBA Professor and Vice Chair, Obstetrics and Gynecology West Virginia University-Charleston Charleston, West Virginia, USA

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References Back S et al. Bull World Health Organ, 2010 Behrman,E et al. Preterm Birth: Consequence, Causes and Prevention. National Academies Press, 2007 Calhoun BC. Abortion and Preterm Birth: Why Medical Journals Aren’t Giving Us the Truth. IORG Briefing Paper. 2012. Calhoun BC, Shadigian E, Rooney B. Induced abortion: cost consequences of an attributable risk for preterm birth and its impact on informed consent and medical malpractice. J Repro Med 2007;52. Chen A, YuanW, Meirik O, Wang X. Wu S, Zhou L, Luo L, Gao E, and Cheng Y. Mifepristone-induced early abortion and outcome of subsequent wanted pregnancy. Am. J. Epidemiol. 2004. Vol. 160, No. 2 Fuchs N, Maymon R, Ben-Ami I, Mendlovic S,Schneider D, Pansky M, Halperin R . Clinical, surgical, and histopathologic outcomes following failed medical abortion. Int J Gynaecol Obstetrics. 2012;117. Hamilton B et al. CDC Vital Statistics Reports, 2012 Hill AB. The environment and disease: Association or causation? Proceed Roy Soc Medicine – London1965:58. Himpens E, Master PT, Van den Broeck C, Oostra A, Calders P, Vanhaesebrouck P. Prevalence, type, distribution of cerebral palsy in relation to gestational age: a meta-analysis review. Develop Med Child Neurol. 2008. Vol 50. Holst D, Garnier Y. Preterm birth and inflammation- the role of genetic polymorphisms. Eur J Obstet Gynecol Biol. 2008:1.

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References Infant Health in America: Everybody’s Business. Hartford, CT:CIGNA Corp 2000 International perspectives on global and reproductive health. 38:1. 2012. Klemetti R, Gissler M, Niinimaki M, Hemminki E. Birth outcomes after induced abortion: a nationwide register-based study of first births in Finland. Human Reproduction, 2012 Liao H, Wei Q, Duan L, Ge J, Zhou Y, Zeng W. Repeated medical abortions and the risk of preterm birth in subsequent pregnancies. Arch Gynecol Obstet 2011;289. Luke B, Bigger H, Leurgas S, Siesma D. The cost of prematurity: a case-control study of twins vs. singletons. AM J Publ Health. 1996:86. Männistö J, Mentula M, Bloigu A, Hemminki E, Gissler M, Heikinheimo O, Niinimäki M. Medical versus surgical termination of pregnancy in primigravid women—is the next delivery differently at risk? A population-based register study. BJOG 2013:120 McCaffrey M. Abortion’s impact on prematurity. Family North Carolina, 2013. March of Dimes. Peristats, as found at: http://www.marchofdimes.com/peristats/Peristats.aspx Niinimäki M, Pouta A, Bloigu A, Gissler M, Hemminki E, Suhonen S, Heikinheimo O. Immediate complications after medical compared with surgical termination of pregnancy. Obstet Gynecol. 2009 ;114. Nour N. Preterm delivery and the MDG. Rev Obstet Gynecol, 2012;5. Oliver-Williams C, Fleming M, Monteath K, Wood AM, et al. Changes in Association between Previous Therapeutic Abortion and Preterm Birth in Scotland, 1980 to 2008: A Historical Cohort Study. PLoS Med 2013; 10.

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References Petrou S, Mehta Z, Hockley C, Cook-Mozaffari P, Henderson J, Goldacre M. Pediatrics 2003;112. Rooney B, Calhoun B. Induced abortion and risk of later preterm births. J Am Phys Surg. 2003;8. Robinson J et al. Risk factors for preterm birth. UptoDate. 2012. 8:2 Shah PS, Zao J. Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analysis. BJOG 2009;116 Swingle HM, Colaizy TT, Zimmerman MB, Morriss FH. Abortion and the risk of subsequent preterm birth: A systematic review with meta-analyses. J Repro Med .2009; 54. Velez DR, Fortunato SJ, Thorsen P, Lombardi SJ, Williams SM, Menon R. Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. PLoSOne. 2008:3. Velez, DR, Fortunato S, Thorsen P, Lombardi SJ, Williams SM, Menon R. Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants. Am J Obstet Gynecol. 2009: 200 Watson LF, Rayner JA, Forster D. Identifying risk factors for very preterm birth: A reference for clinicians. Midwifery 2012 WHO 2012, The Global Action Report on Preterm Birth. Zhou W, Sorenson HT, Olsen J. Induced Abortion and Subsequent Pregnancy Duration. Obstetrics & Gynecology 1999;94.