PRETERM BIRTH AND ABORTION

Mary L Davenport, MD, FACOGMagnificat Maternal Health Program July 31-August 3, 2013 Medical Women’s International Association Seoul, Korea © 2013

Disclosure

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

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

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

Preterm Birth: under 37 weeks

•Extremely preterm < 28 weeks•Very preterm 28-32 weeks•Moderate to late preterm 32 to <37

weeks

60% of preterm births occur in Sub-Saharan Africa and Southern Asia

Nour N. “Preterm delivery and the MDG.” Rev Obstet Gynecol, 2012.

South Africa

More than eight out of ten births are preterm – less than 37 weeks.

WHO 2012, The Global Action Report on Preterm Birth

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.

In the USA we have come a long way….

Patrick Bouvier KennedyAugust 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

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 infantMarch of Dimes, Peristats.Hamilton B et al. CDC Vital Statistics Reports, 2012. Behrman,E et al. Preterm Birth: Consequence, Causes and Prevention. 2007

Kangaroo Care

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):1290-12972Luke 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 20004Himpens 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 .

Long-term impact of Preterm Birth on SurvivorsVisual impairment

Blindness or high myopia after retinopathy of prematurity

Increased hypermetropia and myopia

Hearing impairment (5%–10%)

Chronic lung disease of prematurity (40%)

Reduced lung function

Increased rates of asthma

Long-term poor cardiovascular health and noncommunicable disease

Increased blood pressure, diabetes, pre-eclampsia

Growth failure in infancy, accelerated weight gain in adolescence

Neurodevelopmental effects

Specific learning impairments, dyslexia, reduced academic achievement

Moderate and severe cognitive impairment

Motor impairment

Cerebral palsy

Psychiatric and behavioral sequelae

Attention deficit hyperactivity disorder

Increased anxiety and depression

Nour N. “Preterm delivery and the MDG.” Rev Obstet Gynecol, 2012

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

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.

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

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. 2008Velez DR et al. PLoS One. 2008Velez DR et al. Am J Obstet Gynecol. 2009.

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

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)

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]

Meta-analysis by Shah, et al 200922 PTB StudiesNo 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]

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

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

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

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

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!

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.

Two studies from 2012

Klemetti, et al: preterm birthConclusions:•“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.”

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.

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”

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

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

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

Changes in association of abortion and preterm birth: Scotland 1980-2008

Oliver-Williams C et al. PLoS Medicine, 2013

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.

Oliver-Williams C et al. PLoS Medicine, 2013

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

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

Mifepristone and misoprostol are highly pro-inflammatory

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.

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.

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

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

With thanks toByron C. Calhoun, MD, FACOG, FACS, MBAProfessor and Vice Chair, Obstetrics and GynecologyWest Virginia University-CharlestonCharleston, West Virginia, USA

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African Americans is associated with infection and inflammatory response gene variants. Am J Obstet Gynecol. 2009: 200Watson LF, Rayner JA, Forster D. Identifying risk factors for very preterm birth: A reference for clinicians. Midwifery 2012WHO 2012, The Global Action Report on Preterm Birth.Zhou W, Sorenson HT, Olsen J. Induced Abortion and Subsequent Pregnancy Duration. Obstetrics & Gynecology 1999;94.