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hi everybody this is Chris Morosky in
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this is a short video on preterm birth
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and prematurity I’d like to thank dr.
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Adam Borg eda for his contributions to
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this video the goals and objectives of
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this video are as follows discuss the
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burden of prematurity review the trends
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in Connecticut and national preterm
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birth data understand the risk factors
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and drivers of preterm birth describe
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the tests available to predict preterm
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birth and review the use of progesterone
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to prevent recurrent preterm birth
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preterm birth or prematurity is a single
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most important cause of perinatal
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mortality in the United States it is the
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leading cause of neonatal mortality
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defined as death within the first 28
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days of life in the United States and is
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also the second leading cause of infant
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mortality defined as death in the first
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year of life in the United States
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preterm birth is a major determinant of
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neonatal and infant illness this would
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include neurodevelopmental handicaps
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such as cerebral palsy or mental
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retardation chronic respiratory problems
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intraventricular hemorrhage
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periventricular leukomalacia infection
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retro Lendl fiber aplasia
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necrotizing enterocolitis and neuro
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sensory deficits such as hearing and
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visual prematurity generates enormous
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healthcare costs the average newborn
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hospital charges for a term baby are
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$4,300 vs. 58 thousand dollars for a
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preterm baby the total u.s. Hospital at
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charges for infants days due to
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prematurity in low birth weight or
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almost 12 billion dollars when you
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include maternity and related expenses
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this is often the largest cost to
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employers health care plans as you can
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see infant mortality death in the first
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year of life has decreased in the United
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States since 1915 to 2000 it’s going
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down from proximally one out of ten to
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now one in a thousand live births there
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are multiple reasons for improved
01:57
survival one of these is NICU care we
01:59
now have ventilators total parenteral
02:01
nutrition and surfactant there’s also
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improved obstetrical here we now have
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steroids for lung maturity latency
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antibiotics for preterm premature
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rupture of membranes and we now have
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ultrasounds
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if you look at selected leading causes
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of infant mortality in the United States
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and compare 1996 vs. 2013 what you see
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is that birth defects are down 164 to
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121 per 1000 live births but preterm
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birth and low birth weight is up 99 to
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107 per 100,000 live births SIDS is down
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RDS is down and importantly maternal
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pregnancy complications are very much up
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having gone from 32 to 40 per 100,000
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live births and specifically in
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Connecticut looking at the leading
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causes of infant mortality to our most
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up-to-date data from 2013 you can see
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that Connecticut when compared to the
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United States is very much lower when it
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comes to birth defects preterm birth but
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as higher in SIDS and is about even with
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maternal pregnancy complications preterm
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delivery in Connecticut compared to the
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rest of the United States from 2007 to
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2016 shows that overall our state is
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slightly lower than the national average
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however you can see that both
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Connecticut and the nation have
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approximately nine to ten percent of
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live births that are preterm and when
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broken down by race and ethnicity you
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can see that Asian and Pacific Islanders
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on average from 2013 2015 across the
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nation had an 8.5% preterm birth rate
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white ethnicity had eight point nine
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percent Hispanic ethnicity or race was
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nine point one percent American Indian
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and Alaskan native was ten point five
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percent and black women had a 13.3%
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preterm birth rate what this shows is
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that in the United States the preterm
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birth rate among black women is 49
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percent higher than the rate among all
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other women there are various different
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types of preterm births there is
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spontaneous preterm birth which is the
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spontaneous onset of labor and
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contractions which lead to delivery of
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the infant there’s preterm premature
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rupture of membranes where the water
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breaks prior to the onset of labor and
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then there’s medical intervention or
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what we call indicated preterm birth and
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while the suggests distinct pathways
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many of the risk factors for all three
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are similar what you can see is that
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over time there’s been changes in the
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etiology of preterm birth the
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graphs look at preterm birth from 1989
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to 2001 looking at the graph on the left
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you can see that for the most part all
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preterm births ruptured membranes
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medically indicated and spontaneous
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preterm births seem to be changing
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slightly when you superimpose them on
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themselves and the right graph what you
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can see is that the medically indicated
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preterm births have greatly gone up over
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that time period while all preterm
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births spontaneous preterm births and
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ruptured membranes causing preterm birth
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have either stay the same or slightly
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gone down what this suggests is that
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there may be some changes in the health
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of our mothers over that period of time
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looking at some of the risk factors for
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preterm birth
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if previous preterm birth presents a
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probability of 30 percent of preterm
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birth or subsequent pregnancy greater
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than two previous preterm births
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increases this to 70 percent twin
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gestation x’ has a probability of
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preterm birth of 50% and triplets are
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higher this approaches 75 to 95 percent
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uterine malformations such as a unicorn
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uterus increased the probability of
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preterm birth to 30% looking at maternal
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age for a risk factor for preterm birth
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in the United States from 2013 to 2015
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you can see that for the age groups of
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less than 20 20 to 29 and 30 to 39 the
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percentage of preterm births was pretty
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much steady around 9 to 10 percent
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however looking at women over 40 years
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old this increased greatly to 14.3%
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looking more closely at multiple
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gestation and preterm birth and the
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Connecticut in the United States you can
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see that singleton pregnancies have a
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preterm birth rate of 7.8% as compared
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to sixty point three percent for
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multiple gestation x’ in this time
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period of 2015 you can see that multiple
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gestation is accounted for 3.5% of the
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live births in the United States and 4.1
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percent of the live births in
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Connecticut tobacco smoking is also a
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risk factor for preterm birth there are
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some very interesting trends for
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Connecticut in the United States from
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2006 to 2017 what we can see is that
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overall the percentage of women smoking
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during
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agency has decreased over time and also
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that Connecticut has had a lower
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percentage of women smoking during
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pregnancy compared to the nation also
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looking at BMI and its association with
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preterm birth it can be seen that a low
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BMI is associated with an increased risk
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for spontaneous preterm birth looking at
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a BMI less than 19 the percentage of
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spontaneous preterm birth is sixteen
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point six percent you can see this drop
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to eleven point three percent for BMI of
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nineteen to twenty four point nine eight
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point one percent for normal BMI of 25
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to 29 point nine seven point one percent
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for obesity at thirty to thirty four
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point nine and down to five point two
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for a BMI over thirty-five going with
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this indicated preterm birth is about
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the same but does seem to be slightly
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higher for the BMI of 30 to 34 point
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nine for a long period of time there are
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no tests available to predict premature
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birth
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there are now two recent advances in
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predicting premature birth
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these are fetal fibronectin and cervical
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length measurement we will look at them
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separately first field of fibronectin
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fetal Carrboro nekton is a intracellular
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matrix of the surveys it can be found in
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between the chorion and the decidua as
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shown in the picture it is secreted with
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cervical changes and if absent from the
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vagina there is a very low risk for
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preterm birth FFN is low from 24 to 34
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weeks gestational age it is helpful for
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symptomatic patients therefore that are
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greater than 24 weeks in gestation the
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value of the FFN really isn’t as
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negative predictive value if an F of n
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is negative there is a 98% chance that
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the patient will not deliver in the next
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two weeks and therefore there’s no need
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to spend additional money or resources
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on that patient
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unfortunately the positive predictive
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value is not as helpful and when the
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test is positive there’s a 50% chance
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that the patient will deliver in the
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next two weeks looking at a graph of f
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FN at 24 weeks and the risk for preterm
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birth it is important to keep in mind
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that the cutoff for the FN being
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positive or negative is important in
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terms of how well it performs in
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predicting preterm birth with the black
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line the cutoff for FF n is zero
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with the redline the cutoff for FN is 1
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to 50 with the blue mind the cutoff is
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50 to 200 and the green line is greater
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than 200 so certainly as the
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concentration of your cutoff for F of n
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increases it is more predictive of the
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risk for preterm birth and that women
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who have such high cut-offs such as the
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Green Line certainly at risk for preterm
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birth in a Cochrane review of studies
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evaluating the use of fetal fibronectin
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testing producing the risk of preterm
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birth what they found was in the top
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graph that using FF n did reduce the
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risk of preterm birth less than 37 weeks
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however in reducing the risk of preterm
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birth less than 32 weeks FF n was not
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successful this can be seen in the
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bottom graph and the use of FF n did not
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improve the gestational age at delivery
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in this Cochrane review now moving on to
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a cervical length measurement in a study
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published by James in the New England
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Journal Medicine in 1996 they correlated
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the length of the cervix with the risk
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of preterm birth and you can see that
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the mean cervical eighth was 3.5
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centimeters and that the risk factor for
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preterm birth was approximately 2 to 3
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percent when the cervix was this long as
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the service gradually became shorter and
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shorter and shorter are moving to the
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left side of the graph the relative risk
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for preterm birth increased greatly in
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fact for a woman with a cervical length
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of one point two centimeters the
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relative risk for preterm birth was over
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14 this led to recommendations to screen
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women with a cervical length measurement
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using a transvaginal ultrasound to
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predict the risk of preterm birth while
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this may not be applied generally across
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all populations certainly all women who
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have risk factors for preterm birth are
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recommended to undergo cervical
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screening what that looks like an
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ultrasound is shown in this picture in
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this first picture the vaginal
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ultrasound probe is pressed too far into
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the vagina and compresses the cervix you
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can see the cervix in the middle of the
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screen as the greyish mass in the middle
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of the ultrasound screen with the white
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line running through it representing the
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end of cervical canal as the vaginal
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probe is pulled out slightly from the
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vagina you can begin to see some
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the amniotic fluid near the internal
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offering up as a black triangle with
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some pressure on the fundus of the
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uterus being transmitted through the
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pregnancy down to the cervix you can see
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now a black funneling of the inner
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portion of the cervix the cervical
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length is then measured as the white
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line of the part of the service that is
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closed and this is called the functional
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length of the cervix in this image that
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the cervical length is two point six
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centimeters and this is slightly
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shortened we will end this video by
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discussing progesterone for the
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prevention of preterm birth there is
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recent evidence to suggest that
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progesterone maintains uterine
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quiescence progesterone inhibits the
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production of prostaglandins it also
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inhibits the production of contraction
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associated protein genes such as
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oxytocin and prostaglandin receptors gap
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junctions and ion channels it down
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regulates the production of calcium
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channels and therefore decreases uterine
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contractions looking at some of the
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historical Studies on the use of
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progesterone for the Prevention of
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recurrent preterm birth this goes back
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to the 1970s when pepper Nick and
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colleagues published a placebo
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controlled trial of 99 women in the
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third trimester who were given 17 alpha
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hydroxy progesterone capri and they
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found that this was efficacious for
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preventing preterm birth in 1975 Johnson
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at all published in the New England
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Journal of Medicine that initiating 17
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hydroxy progesterone in the second
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trimester prevented preterm birth from
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1980 there was a study that showed that
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this was not efficacious for preventing
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preterm birth in twins and a 1989
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meta-analysis said that this was still
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unclear more recent studies were
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published in 2003 and the papers shown
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here by Mesa dal as one of the landmark
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studies around progesterone for the
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Prevention of preterm birth this was run
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out of the National Institutes of child
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and health development and the maternal
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fetal medicine University and this was a
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randomized double-blind
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placebo-controlled trial women were
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enrolled at 16 to 20 weeks and were
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either given placebo or
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250 milligrams of 17 hydroxy
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progesterone
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all through weekly injections and the
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primary outcome for the study of a
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spontaneous preterm birth less than 37
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2980 women are eligible for the study
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1039 met entry criteria and 463
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consented for the trial in cutting to
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the chase delivery before 37 weeks was
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greatly reduced by the use of
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progesterone by a total of 34 percent
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delivery before 35 weeks gestational age
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was reduced by 33 percent and delivery
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before 32 weeks gestational AIDS was
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decreased by 42 percent all of these
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results were statistically significant
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in a separate study by dave fonseca at
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all this is also pops in 2003 they
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looked at you do vaginal progesterone in
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a randomized double-blind
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placebo-controlled study out of Brazil
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they looked at 142 high-risk singleton
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pregnancies and these patients were
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either given 100 milligrams of vaginal
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progesterone or placebo daily the
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vaginal suppositories
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contained 100 milligrams of natural
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progesterone and it was applied nightly
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from 24 to 34 weeks what they found was
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that there was again a decreased risk of
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preterm birth less than 37 weeks in the
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progesterone group 28.5% for placebo
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13.8% for progesterone there was also a
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decreased incidence of preterm birth
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less than 34 weeks 18.6% for placebo and
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2.8 percent for progesterone and these
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were significantly different looking at
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the cumulative deliveries you can see
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that the progesterone group had more
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undelivered patients compared to the
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placebo group this again was too
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distantly sniffing in brief summary of
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progesterone
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it appears that randomized studies show
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benefit to using 17 hydroxy progesterone
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in vaginal progesterone in patients with
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a short cervix or with a history of
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preterm birth rain in my studies so far
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showed no benefit in using progesterone
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for patients with twins triplets or if a
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stitch called a cerclage is placed in
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the cervix so importantly what we can do
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as providers and decreasing preterm
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birth is to recommend our patients to
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stop smoking improve their BMI and
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nutrition and take a good history
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spontaneous preterm birth and find women
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with short services and offer them
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progesterone the take-home messages here
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are that all women are at risk for
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preterm labor and birth the rate of
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preterm labor in birth is rising mostly
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due to indicated preterm births we know
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now that 700c progesterone and vaginal
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progesterone may be beneficial in
15:56
certain populations and really everybody
15:58
should just stop smoking so wrapping it
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up I think we did meet our goals and
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objectives they were to discuss the
16:05
burden of prematurity review the trends
16:07
in Connecticut and national preterm
16:08
birth data understand the risk factors
16:10
and drivers of preterm birth describe
16:13
the tests available to predict preterm
16:14
birth and review the use of progesterone
16:16
to prevent recurrent preterm birth thank
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you for watching this video we hope you
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found it helpful good luck with their
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studies and we’ll be seeing you soon in
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class