Chapter 1. Overview of Obstetrics
BS. Nguyễn Hồng Anh
Te science and clinical practice o obstetrics ocuses on human
reproduction. Te specialty promotes the health and well-being
o the pregnant woman and her etus through quality perinatal
care. Such care entails recognition and treatment o complications, supervision o labor and delivery, initial care o the newborn, and management o the puerperium. Postpartum care
promotes health and provides amily planning options.
Evidence-based medicine dominates the modern practice o
obstetrics. As described by Williams in this textbook’s rst edition, we too strive to present the scientic evidence or current
obstetrical care. Still, high-quality data do not support most
recommendations (Brock, 2021). Tus, much o our practice
stems rom expert-based opinions and historical experiences
(Society or Maternal-Fetal Medicine, 2021). o help bridge
knowledge gaps, we also rely on authoritative sources such as
the American College o Obstetricians and Gynecologists and
the Society or Maternal-Fetal Medicine, as well as agencies
such as the Centers or Disease Control and Prevention (CDC)
and National Institutes o Health (NIH).
VITAL STATISTICS
Te importance o obstetrics is demonstrated by the use o
maternal and neonatal outcomes as an index o health and
lie quality among nations. Intuitively, indices showing poor
obstetrical and perinatal outcomes could be assumed to reect
medical care deciencies or the entire population.
Te National Vital Statistics System o the United States
collects statistics on births and deaths, including etal deaths.
Legal authority or collection resides individually with the 50
states; two regions—the District o Columbia and New York
City; and ve territories—American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, and the Virgin Islands. Te
standard birth certicate includes inormation on medical and
liestyle risks, labor and delivery actors, and newborn characteristics. Importantly, the current death certicate contains a
pregnancy checkbox (Hoyert, 2020).
■ Definitions
Standard denitions are encouraged by the World Health Organization as well as the American Academy o Pediatrics and the
American College o Obstetricians and Gynecologists (2019a).
Uniormity allows data comparison between states or regions and
between countries. Still, not all denitions are uniormly applied.
For example, uniormity is incomplete among states regarding birthweight and gestational age criteria or reporting etal
deaths (American College o Obstetricians and Gynecologists,
2020a). Not all states ollow this recommendation. Specically,
28 states stipulate that losses beginning at 20 weeks’ gestation
should be recorded as etal deaths; eight states report all products
o conception as etal deaths; and still others use a minimum
birthweight o 350 g, 400 g, or 500 g to dene etal death. o
urther the conusion, the National Vital Statistics Reports tabulates etal deaths rom pregnancies that are 20 weeks’ gestation
or older (Centers or Disease Control and Prevention, 2020a).
Tis is problematic because the 50th percentile or etal weight
at 20 weeks approximates 325 to 350 g—considerably less than
the 500-g denition. In act, a birthweight o 500 g corresponds
closely with the 50th percentile or 22 weeks’ gestation.Overview of Obstetrics 3
CHAPTER 1
Denitions recommended by the National Center or
Health Statistics and the CDC are as ollows:
Perinatal period. Te interval between the birth o a neonate
born ater 20 weeks’ gestation and the 28 completed days
ater that birth. When perinatal rates are based on birthweight, rather than gestational age, recommendations dene
the perinatal period as commencing at the birth o a 500-g
neonate.
Birth. Te complete expulsion or extraction rom the mother o
a etus ater 20 weeks’ gestation. As described above, in the
absence o accurate dating criteria, etuses weighing <500 g
are usually not considered births but rather are termed abortuses or purposes o vital statistics.
Birthweight. Neonatal weight determined immediately ater delivery or as soon thereater as easible. It should be expressed
to the nearest gram.
Birth rate. Te number o live births per 1000 population.
Fertility rate. Te number o live births per 1000 emales aged
15 through 44 years.
Live birth. Te term used to record a birth whenever the newborn at or sometime ater birth breathes spontaneously or
shows any other sign o lie such as a heartbeat or denite
spontaneous movement o voluntary muscles. Heartbeats are
distinguished rom transient cardiac contractions, and respirations are dierentiated rom eeting respiratory eorts
or gasps.
Stillbirth or etal death. Te absence o signs o lie at birth.
Early neonatal death. Death o a liveborn neonate during the
rst 7 days ater birth.
Late neonatal death. Death ater 7 days but beore 29 days.
Stillbirth rate or etal death rate. Te number o stillborn neonates per 1000 neonates born, including live births and stillbirths.
Neonatal mortality rate. Te number o neonatal deaths per
1000 live births.
Perinatal mortality rate. Te number o stillbirths plus neonatal
deaths per 1000 total births.
Inant death. All deaths o liveborn inants rom birth through
12 months o age.
Inant mortality rate. Te number o inant deaths per 1000
live births.
Low birthweight. A newborn whose weight is <2500 g.
Very low birthweight. A newborn whose weight is <1500 g.
Extremely low birthweight. A newborn whose weight is <1000 g.
erm neonate. A neonate born any time ater 37 completed
weeks’ gestation and up until 42 completed weeks’ gestation
(260 to 294 days). Te American College o Obstetricians
and Gynecologists and Society or Maternal-Fetal Medicine
encourage specic gestational age designations (2019a). Early
term reers to neonates born at 37 completed weeks up to
386/7 weeks. Full term denotes those born at 39 completed
weeks up to 406/7 weeks. Last, late term describes neonates
born at 41 completed weeks up to 416/7 weeks.
Preterm neonate. A neonate born beore 37 completed weeks
(the 259th day). A neonate born beore 34 completed weeks
is early preterm, whereas a neonate born between 34 and 36
completed weeks is late preterm.
Postterm neonate. A neonate born any time ater completion o
the 42nd week, beginning with day 295.
Abortus. A etus or embryo removed or expelled rom the uterus
in the rst hal o gestation—20 weeks or less, or in the absence
o accurate dating criteria, born weighing <500 g.
Induced termination o pregnancy. Te purposeul interruption
o an intrauterine pregnancy that has the intention other
than to produce a liveborn neonate and that does not result
in a live birth. Tis denition excludes retention o products
o conception ollowing etal death.
Direct maternal death. Te death o the mother that results
rom obstetrical complications o pregnancy, labor, or the
puerperium and rom interventions, omissions, incorrect
treatment, or a chain o events resulting rom any o these
actors. An example is maternal death rom exsanguination
ater uterine rupture.
Indirect maternal death. A maternal death that is not directly
due to an obstetrical cause. Death results rom previously
existing disease or a disease developing during pregnancy,
labor, or the puerperium that was aggravated by maternal
physiological adaptation to pregnancy. An example is maternal death rom complications o mitral valve stenosis.
Late maternal death. Death o a woman rom direct or indirect
obstetrical causes more than 42 days but less than 1 year ater
the pregnancy’s end.
Nonmaternal death. Death o the mother that results rom accidental or incidental causes not related to pregnancy. An
example is death rom an automobile accident or concurrent
malignancy.
Pregnancy-associated death. Te death o a woman, rom any
cause, while pregnant or within 1 calendar year o termination o pregnancy, regardless o the duration and the site o
pregnancy.
Pregnancy-related death. A pregnancy-associated death that
results rom: (1) complications o pregnancy itsel, (2) the
chain o events initiated by pregnancy that led to death, or
(3) aggravation o an unrelated condition by the physiological or pharmacological eects o pregnancy and that subsequently caused death.
Maternal mortality ratio. Te number o maternal deaths that
result rom the reproductive process per 100,000 live births.
Used more commonly, but less accurately, are the terms maternal mortality rate or maternal death rate. Te term ratio
is more accurate because it includes in the numerator the
number o deaths regardless o pregnancy outcome—or
example, live births, stillbirths, and ectopic pregnancies—
whereas the denominator includes the number o live births.
PREGNANCY RATES IN THE UNITED STATES
According to the CDC, the ertility rate o women aged 15
to 44 years in the United States in 2019 was 58 live births
per 1000 women. Tis rate began slowly trending downward
in 1990 and has now dropped below that or replacement
births to sustain the population level. Tis indicates a population decline. Te birth rate decreased or all major ethnic and
racial groups, or adolescents and unmarried women, and or4 Overview
Section 1
those aged 20 to 24 years. For women older than 30 years, the
birth rate rose slightly. Almost hal o newborns in 2019 in the
United States were minorities: Hispanic—25 percent; AricanAmerican—15 percent; and Asian—4 percent (Martin, 2021).
Te total number o pregnancies and their outcomes in
2019 are shown in Table 1-1. According to the Guttmacher
Institute (2019b), 45 percent o births in the United States
are unintended at the time o conception. But, the overall proportion o unintended births has declined since 2008. Unmarried women, black women, and women with less education or
income are more likely to have an unplanned pregnancy.
OBSTETRICAL CARE MEASURES
Several indices are used to assess obstetrical and perinatal outcomes as measures o medical care quality. As noted, the perinatal mortality rate includes the number o stillbirths and neonatal
deaths per 1000 total births. In 2016, this rate was 6 deaths
per 1000 births (Fig. 1-1). Tis rate has been unchanged or
several years (Gregory, 2018). Rates o etal death at 28 weeks’
gestational age or more have declined since 1990, whereas rates
or those between 20 and 27 weeks are static.
O infant deaths, the rate approximated 6 deaths per 1000
live births in 2018 compared with nearly 7 in 2001 (Centers
or Disease Control and Prevention, 2020b). Te our leading
causes—congenital malormations, preterm birth, low birthweight, and maternal pregnancy complications—accounted or
almost hal o all inant deaths. Neonates born at the lowest gestational ages and birthweights add substantively to these mortality rates. For example, 17 percent o all inant deaths in 2018
were in those born preterm and with a low birthweight (Centers or Disease Control and Prevention, 2020d). O particular interest are neonates with birthweights <500 g, or whom
neonatal intensive care can now be oered (Chap. 45, p. 785).
O maternal deaths, rates dropped precipitously in the United
States during the 20th century. Pregnancy-related deaths are so
uncommon as to be measured per 100,000 births. Te CDC
maintains data on pregnancy-related maternal deaths in its
Pregnancy Mortality Surveillance System (PMSS). Its latest
report described 3410 pregnancy-related deaths between 2011
and 2015 (Petersen, 2019b). Approximately 5 percent were
early-pregnancy maternal deaths due to ectopic gestation or
abortive outcomes. Te deadly obstetrical triad o hemorrhage,
preeclampsia, and inection accounted or a third o all deaths
(Fig. 1-2). Tromboembolism, cardiomyopathy, and other cardiovascular disease together accounted or another third. Other
signicant contributors were amnionic uid embolism (5.5
percent) and cerebrovascular accidents (8.2 percent). Anesthesiarelated deaths were at an all time low—only 0.4 percent. Similar
TABLE 1-1. Total Pregnancies and Outcomes in the
United States in 2019
Outcome Number or Percent
Total births 3,747,540
Cesarean deliveries 31.7%
Primary cesarean delivery 21.6%
Vaginal birth after cesarean 13.8%
Preterm births (<37 weeks) 10.0%
Low birthweight (<2500 g) 8.0%
Very low birthweight (<1500 g) 1.4%
Induced abortions 862,320
Data from Guttmacher 2019b; Martin, 2021.
8 6 4 2 0
Perinatal
Rate per 1000 births
Late fetal
6.0
2.9 3.1
Early neonatal
FIGURE 1-1 Perinatal, late-fetal, and early-neonatal mortality rates
per 1000 births in the United States in 2016. (Data from Gregory, 2018).
20
15
10
5 0
Hemorrhage
Preeclampsia
Infection
Cardiovascular
Cardiomyopathy
Thromboembolism
Stroke
Percent
Cause of pregnancy-related deaths
10.7
6.6
12.7
15.5
11.5
9.6
8.2
FIGURE 1-2 Some causes of and their contributions to pregnancyrelated maternal deaths in the United States from 2014–2017. (Data
from Centers for Disease Control and Prevention, 2020c).Overview of Obstetrics 5
CHAPTER 1
causes were reported or selected cohorts by MacDorman and
associates (2017).
Te pregnancy-related maternal mortality ratio was 17 deaths
per 100,000 live births in 2017 (Fig. 1-3). Te cause o this
rise during the last 30 years may simply be that more women
are dying, however, other actors explain this increase (Joseph,
2017). First, the number o pregnant women with severe
chronic health conditions, which place women at higher risk,
is greater (Centers or Disease Control and Prevention, 2020c).
Second, the increased proportion o births to women older than
40 years contributes to higher mortality rates (Petersen, 2019b).
Another is an articial elevation caused by the International
Statistical Classication o Diseases, 10th Revision (ICD-10),
implemented in 1999. Additionally, improved reporting o
maternal mortality contributes to the rise (MacDorman, 2016,
2017). Last, implementation o the pregnancy checkbox on the
death certicate was associated with an increased identication
o maternal deaths (Rossen, 2020). Tus, ater accounting or
the checkbox, predicted maternal mortality rates did not change
signicantly rom 1999 through 2017.
Another consideration is the obvious disparity o higher
mortality rates among black, Hispanic, and white women as
shown in Figure 1-4. Racial disparities stem rom health-care
availability, access, or use (Petersen, 2019a). Te maternal mortality rate is also disparately high in rural compared with metropolitan areas (Maron, 2017).
Importantly, many maternal deaths are considered preventable. In one report, up to a third o pregnancy-related deaths
in white women and up to hal o those in black women were
deemed preventable (Berg, 2005). One evaluation o an insured
cohort reported that 28 percent o 98 maternal deaths were
preventable (Clark, 2008). Tus, urther eorts are imperative
or obstetrics and described on page 6.
■ Severe Maternal Morbidity
Tis is dened as unintended events o labor and delivery resulting in serious short- or long-term consequences to a woman.
Indicators serve as one measure to guide prevention (Table 1-2).
Te American College o Obstetricians and Gynecologists and the
Society or Maternal-Fetal Medicine (2016) have provided lists o
suggested screening topics or this purpose.
o study severe maternal morbidity (SMM), the CDC analyzed more than 50 million maternity records rom 1998 to
2009 (Callaghan, 2012). Tey reported that 129 per 10,000
women had at least one indicator or SMM (able 1-2). Tus,
or every maternal death, approximately 200 women experience
severe morbidity. As shown in Figure 1-5, SMM rates have
increased during the past 15 years, and this trend is attributed
to better documentation and a rise the blood transusion rate.
Tese numbers are greatest in smaller hospitals with <1000
deliveries annually (Hehir, 2017). Last, as with mortality rates,
19
17
15
13
11
9 9
2000 2004 2008 2012 2016
Year
Pregnancy-related deaths
per 100,000 lives
FIGURE 1-3 Trends in pregnancy-related maternal mortality in
the United States from 1999–2017. (Data from Centers for Disease
Control and Prevention, 2020c).
Black
0
15
30
45
American
Indian
White Hispanic/
Latino
Pregnancy-related deaths
per 100,000 live births
FIGURE 1-4 Pregnancy-related mortality ratio by race/ethnicity in
the United States from 2014–2017. (Data from Centers for Disease
Control and Prevention, 2020c).
TABLE 1-2. Severe Maternal Morbidity Indicators
Acute myocardial infarction
Acute renal failure
Adult respiratory distress syndrome
Amnionic fluid embolism
Cardiac arrest/ventricular fibrillation
Cardiac monitoring
Cardiac surgery
Conversion of cardiac rhythm
Disseminated intravascular coagulation
Eclampsia
Heart failure during procedure
Hysterectomy
Injuries of thorax, abdomen, and pelvis
Intracranial injuries
Puerperal cerebrovascular disorders
Pulmonary edema
Severe anesthesia complications
Sepsis
Shock
Sickle-cell crisis
Thrombotic embolism
Tracheostomy
Ventilation
Summarized from the Centers for Disease Control and
Prevention, 2021.6 Overview
Section 1
there are serious racial and ethnic disparities or SMM, and
black women are disproportionately aected (Creanga, 2014).
■ Near Misses
Lowering medical error rates serves to diminish risks or maternal death and SMM. Te terms near misses or close calls were
introduced and dened as unplanned events caused by error
that do not result in patient injury but have this potential (Institute or Sae Medication Practices, 2009). Tese are more common than injury events, but or obvious reasons, they are more
difcult to identiy and quantiy. Systems designed to encourage
reporting have been installed in various institutions and allow
ocused saety eorts (Clark, 2012; King, 2012; Shields, 2017).
Te World Health Organization (WHO) also implemented
such a system. It has been validated in Brazil and accurately correlates with maternal death rates (Souza, 2012). A similar system in Britain is the UK Obstetric Surveillance System—UKOSS
(Knight, 2005, 2008). In the United States, one is the National
Partnership for Maternal Safety (D’Alton, 2016; Main, 2015).
TIMELY TOPICS IN OBSTETRICS
Various topics have been in the oreront since the 25th edition
o this textbook. Here, we discuss several o these.
■ COVID19 Pandemic
In early 2020, the severe acute respiratory syndrome (SARS)-
CoV-2 virus spread rapidly around the globe, creating the greatest public health crisis since the inuenza pandemic o 1918
(Chap. 67, p. 1187). As o early 2021, the disease caused by
this virus and commonly known as COVID-19 is estimated to
have inected more than 181 million people and caused nearly
4 million deaths (World Health Organization, 2021). Expectedly, the healthcare and political landscapes in the United
States changed dramatically because o the pandemic.
Following the January 2020 declaration o a Global Health
Emergency by the WHO, citywide lockdowns, state-mandated
shelter-in-place orders, and public mask mandates were all implemented to help control early viral spread. Healthcare systems
scrambled to acquire COVID-19 tests and personal protective
equipment or sta. Wards dedicated solely to COVID-19 care
opened in hospitals throughout the nation to handle substantial patient volume. Despite these measures, more than 500,000
individuals—including more than 3000 healthcare workers—
died in the United States in 2020 rom the inection.
Maternity wards were not spared, and traditional models o
prenatal care were transormed. Namely, virtual care and drivethrough prenatal care models aimed to reduce exposure risk to
patients and sta (Holcomb, 2020; urrentine, 2020). Asymptomatic or mild inections were common in pregnancy (Adhikari,
2020). Still, the eects o COVID-19 on pregnancy are not completely understood, and the eect o pregnancy on disease course
is controversial. Management o severe COVID-19 inection in
pregnancy requires interdisciplinary care and an understanding o
pregnancy physiology and viral pathophysiology.
Preventive measures—including mRNA vaccines—have
been shown to be sae and highly eective in disease prevention. However, this critical inormation was delayed ollowing exclusion o pregnant individuals rom initial clinical trials
(Adhikari, 2021; Polack, 2020). In a report describing over
800,000 pregnancies, Chinn and colleagues (2021) ound that
2.2 percent (18,715) o these women had COVID-19. When
compared with women without such inections, these women
had signicantly increased adverse outcomes to include preterm
birth, ICU admissions, intubations and mechanical ventilation,
and maternal deaths. In 2021 the FDA approved COVID-19
vaccines or pregnant women.
Knowledge gained during the SARS-CoV-2 pandemic will
undoubtedly shape healthcare moving orward (Cook, 2021).
Indeed, a combined in-person plus audio-only virtual prenatal
care model may most eectively provide services to vulnerable
patients who lack internet access (Duryea, 2021).
■ Maternal Mortality—a Call to Arms
Almost 700 women in the United States die each year rom
pregnancy or its complications, and many deaths are deemed
preventable. As a result, obstetricians and other stakeholders have united to address these tragedies (Chescheir, 2015).
Because maternal deaths are inextricably linked to SMM indicators (see able 1-2), several programs have been designed
by national organization to avoid these events. Noted earlier,
the Pregnancy Mortality Surveillance System (PMSS) collects national pregnancy-related death data to guide prevention eorts. Another, the Alliance or Innovation on Maternal
Health (AIM) program, creates patient safety bundles, which
describe evidence-based best practices or various obstetrical
settings. Te Joint Commission recommends that birthing centers establish protocols and implement simulation eorts (Barbieri, 2015). Moreover, national working groups target specic
risks, such as thromboembolism (D’Alton, 2016).
In addition to pregnancy, the puerperium is a vulnerable period as well. One specic national eort is to establish
0
20
Overall rate of severe maternal
morbidity with blood transfusions
Blood
transfusions
Severe maternal morbidity
40 without blood transfusions
60
80
100
120
140
160
1993
1995
1997
1999
2001
2003
2004
2006
2008
2010
2012
2014
SMM per 10,000 delivery hospitalizations
FIGURE 1-5 Rates of severe maternal morbidity (SMM) per 10,000
delivery hospitalizations. Women who received blood transfusions
account for the greatest fraction of SMM. (Data from Centers for
Disease Control and Prevention, 2021).Overview of Obstetrics 7
CHAPTER 1
dedicated 1-year postpartum ollow-up to ensure ongoing care.
Important targets are medical disorders such as hypertension,
diabetes, other cardiovascular diseases, and their consequences.
o emphasize puerperal care, the concept o a “ourth trimester”
has been introduced (Chap. 36, p. 634). Moreover, legislation—
the MOMMA’s Act—aims to expand Medicaid postpartum
coverage rom 60 days to 12 months (Bailey, 2021). As stated
by Surgeon General Jerome Adams, “We must act now; our
nation and our mothers deserve better.” (Frieden, 2020).
■ Opioid Use Disorder
During 1999 to 2014, the national prevalence o opioid use
disorder in pregnant women rose 333 percent rom 1.5 to 6.5
cases per 1000 deliveries (Centers or Disease Control and
Prevention, 2018). In addition to the complexities o maternal addiction, opioid use has led to an unprecedented increase
in the incidence o the neonatal opioid withdrawal syndrome
(Chap. 33, p. 605). o combat the associated adverse eects on
women and their pregnancies, the American College o Obstetricians and Gynecologists (2019b) has stressed an active role
by obstetricians. Te College recommends universal screening
by questionnaire, as well as care given to aected women by
a multidisciplinary team. Terapeutic use o opioids is curtailed as best possible. reatment o opioid use disorder with
methadone or buprenorphine is challenging and discussed
in Chapter 64 (p. 1150). Despite eorts, a signicant decline
in the prevalence o these disorders in gravidas is not in sight.
■ Advances in Prenatal Genetics
Several technologies help detect etal genetic abnormalities.
Since the last edition, noninvasive prenatal screening that uses
cell-ree DNA (cDNA) has become commonplace in prenatal
care (Zhang, 2019). Another promising technique is chromosomal microarray analysis (CMA) perormed on samples o
chorionic villi or amnionic uid. Tese tests provide sophisticated inormation about gains and losses o DNA segments
as small as 50 to 100 kilobases. However, although the yield
with CMA is superior to that with etal karyotyping, most birth
deects occur in the setting o normal CMA and karyotype
results.
As knowledge o the human genome has expanded, the
role o specic DNA sequence abnormalities has gained attention. As an example, evaluation o etal skeletal dysplasia may
include panels o tests in which next-generation sequencing
is used to identiy mutations in specic genes. Whole exome
sequencing (WES) analyzes all coding regions o DNA, which
together account or 1.5 percent o the genome. In pregnancies with structural etal abnormalities, and in which CMA and
karyotype results are normal, WES has identied clinically signicant abnormalities in approximately 10 percent o etuses
(Lord, 2019; Petrovski, 2019). In one series o etuses with
unexplained nonimmune hydrops, WES detected diagnostic
genetic variants in nearly 30 percent (Sparks, 2020).
Although promising, WES technology at this time is not
recommended or routine use in prenatal diagnosis (American
College o Obstetricians and Gynecologists, 2020b). Limitations
include high rates o genetic variants o uncertain signicance,
long turnaround times, and high costs. Comprehensive counseling is needed because WES may detect or suspect a nding
that is unrelated but medically actionable. Genomic tests are
reviewed in Chapter 16 (p. 324), and elements o counseling
are discussed in Chapter 17 (p. 334).
■ Placenta Accreta Spectrum
Since our last edition, the cesarean delivery rate has been static
and approximates 32 percent. However, rates o pregnancies
complicated by placenta accreta spectrum (PAS) have grown
substantially. An incidence as high as 1 case in 300 deliveries
has been cited (American College o Obstetricians and Gynecologists, 2018). Sequelae o these dangerous syndromes are
discussed in Chapter 43 (p. 765). o address these risks, specialized accreta surgical teams at tertiary care centers and greater
antepartum transer to these centers are both on the rise. As
one prevention, national eorts have worked to avoid the primary cesarean delivery. However, despite these eorts, PAS will
likely continue as a signicant risk or SMM.
■ Progestogens to Prevent Preterm Birth
Progesterone derivatives to orestall preterm birth have been
studied or decades. One—intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC)—was approved by the U.S.
Food and Drug Administration (FDA) under the accelerated
approval process and contingent on demonstration o efcacy in a second trial. Te drug is marketed as Makena, and
subsequent, observational studies, described in Chapter 45
(p. 795), have led to questions o its efcacy (Nelson, 2021).
In 2019, results o the conrmatory trial o Makena
e fcacy—the PROLONG trial—ailed to show its benets
compared with placebo or prevention o birth beore 35 weeks
(Blackwell, 2020). Later in 2019, an FDA Advisory Committee
voted 9 to 7 to withdraw interim accelerated approval. Analyses by the committee included cross-study comparisons and
subgroup analyses that did not show 17-OHPC benets (Fig.
45-6, p. 796). In late 2020, the FDA Center or Drug Evaluation and Research (CDER) recommended drug withdrawal
rom the market.
Subsequently, obstetricians became polarized regarding “o
label” use o the drug because it appears safe (Chang, 2020;
Greene, 2020; Sibai, 2020). Despite ndings rom the PROLONG trial and the FDA’s CDER, both the American College o Obstetricians and Gynecologists (2021) and the Society
or Maternal-Fetal Medicine (2020) continued to endorse
17-OHPC use. Tis, however, is with the proviso that “uncertainty regarding benet” be shared with the patient during
decision-making. Last, the EPPPIC Group (2021) perormed
a metaanalysis o randomized trials evaluating progestogens
or preterm birth prevention. Although not statistically signi-
cant, they concluded progestogens, which include 17-OHPC,
reduced births at less than 34 weeks. Te FDA’s CDER (2021)
continues to recommend withdrawal o 17-OHPC rom the
market. At this time, however, thousands o women continue
to receive 17-OHPC despite its questionable efcacy.
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