High-Order Multiple Gestations John P. Elliott, MD

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High-Order Multiple Gestations
John P. Elliott, MD
Infertility treatments have produced an increase in multiple gestations with twins accounting for 3.3% of births in the United States in 2002. Over that same time period, premature
deliveries increased from 10.7% in 1992 to 12.1% in 2002. High-order multiple gestations
have also increased, and virtually all of those deliver prematurely. Clinicians are facing the
challenge of managing these complicated pregnancies. Neonatal outcome will primarily
depend on the gestational age at delivery and the birth weight of the babies. Care is
directed at aggressively and proactively preventing preterm delivery. Ultrasound assessments are made frequently to assess fetal anatomical abnormalities, nuchal translucency,
fetal growth, cervical length, amniotic fluid, and biophysical profile. Stress reduction and
activity reduction will decrease uterine activity, and tocolytic drugs are employed to
decrease background contractions to reduce preterm labor (PTL). Fetal fibronectin testing
helps predict risk of PTL, and magnesium sulfate tocolysis is used in aggressive dosing to
arrest PTL if it occurs. Outcomes are presented and discussed. Successful outcomes are
not only possible, but probable.
Semin Perinatol 29:305-311 © 2005 Elsevier Inc. All rights reserved.
KEYWORDS multiple gestation, high order multiple gestation, twins, triplets, quadruplets
T
he incidence of multiple gestation has increased dramatically in the last 25 years. The reasons for this increase
include the choice of many women to delay childbearing
while advancing their careers and, more importantly, new
technologies and advances in reproductive medicine that
overcome infertility.1 The incidence of multiple births increased from 2.4% of all births in 1992 to 3.3% (38% increase) in 2002 in the United States.2 Over that same time
period, the preterm birth rate in the US increased from 10.7%
of live births to 12.1%.1 Approximately 94% of multiple gestations are twins, which deliver preterm about 55% of the
time. Thus, the majority of the increase in premature delivery
noted from 1992 to 2002 is due to the increase in multiple
gestations. Preterm delivery (PTD) places the babies at risk
for short- and long-term morbidity and mortality. Intraventricular hemorrhage (IVH), periventricular leukomalacia
(PVL), cerebral palsy, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and respiratory distress syndrome (RDS) are complications of prematurity that can result
in permanent injuries, including cerebral palsy, mental retardation, chronic lung disease, and loss of vision and hearing.
Department of Obstetrics and Gynecology, Banner Good Samaritan Medical
Center, Phoenix, AZ.
Address reprint requests to John P. Elliott, MD, Department of Obstetrics
and Gynecology, Banner Good Samaritan Medical Center, 1111 E. McDowell Road, Phoenix, AZ 85006. E-mail: [email protected]
bannerhealth.com
0146-0005/05/$-see front matter © 2005 Elsevier Inc. All rights reserved.
doi:10.1053/j.semperi.2005.08.001
Multiple gestation contributes disproportionally to the PTD
rate. The National Vital and Health Statistics report1 documents that in 2002 there were 6898 triplet deliveries (0.2% of
all liveborn deliveries), 434 quadruplets (0.01%), and 69
quintuplets (0.001%). These pregnancies are considered
high-order multiple (HOM) gestations. Garite and coworkers3 demonstrated in a large database of newborns (51,388)
from Pediatrix Medical Group that gestational age-specific
mortality and survival without significant morbidity are similar for singleton, twins, and triplets, establishing that the
determining factor affecting neonatal outcome is prematurity. Outcome was determined by the gestational age at delivery, with twins or triplets having a greater chance of delivering prematurely. This chapter will present information
about HOM pregnancies and recommendations for management, which must address issues of fetal growth and prematurity prevention.
There are four factors that will affect outcome in HOM
gestations. The height of the mother influences the weight of
the babies as reported by Blickstein and coworkers,4 who
documented heavier birth weight and a lower risk of delivering very low birth weight triplets if maternal height was
taller than 165 cm. In unpublished data from our practice,
there is a greater gestational age at delivery if the maternal
height is 5 feet, 3 inches or greater.
Parity is an important influence on gestational age at delivery. Patients with a history of one or more term deliveries
305
J.P. Elliott
306
Table 1 Effect of Parity on Gestational Age at Delivery in High
Order Multiple Gestations
Author
Gest. Age Difference
Parous > Nulliparous
Ron-El, et al (1981)5
Gonen, et al (1990)6
McKeown, et al (1952)7
Elliott, et al (1992)8
Aina-Mumuny, et al (2004)9
2 week
2 week
1 week
1.4 week
3 week
have an advantage in carrying a HOM gestation. Table 1
summarizes data from five publications5-9 that reported outcome data based on parity. One to three weeks extra time was
achieved by the parous women. Unfortunately, in our practice, 92% of our HOM gestations were nulliparous, negating
that advantage.
The most important factor that affects gestational age at
delivery is the number of live fetuses (Table 2). This fact is
illustrated by a report by Collins and Bleyl10 that reported
outcome data on 71 quadruplet pregnancies. The mean gestational age at delivery was reported to be 31.4 weeks, but if
all pregnancies that did not deliver 4 live babies were excluded from the analysis, the mean gestational age at delivery
dropped to 29.7 weeks. The excluded pregnancies delivered
at a gestational age that corresponded to the expected age for
the number of live babies.
The final influence on outcome is placentation. The safest
type of placentation has 1 placenta for each sac and baby
(dichorionic/diamniotic). Blastocyst transfer can result in
twinning of 1 or more embryos that will be beyond day 3 of
embryonic life when the twinning occurs, which will result in
monochorionic/diamniotic placentation. Anytime there are 1
or more monochorionic placentas, the risk of twin--twin
transfusion syndrome (TTTS) is added to the risks of the
HOM gestation. Acute, severe TTTS develops in about 15%
of monochorionic diamniotic twins. Heyborne and colleagues11 reported a diagnosis of TTTS in 3 of 96 (3.1%) of
monochorionic/monoamniotic twin pregnancies. In our experience, TTTS occurs in HOM pregnancies slightly later
(22-27 weeks) than in monochorionic/diamniotic twin gestations (16-24 weeks), and responded better to intervention
with therapeutic amniocentesis.
Management of HOM Gestation
Prenatal care of a patient carrying a HOM pregnancy will
differ in many respects from a low-risk singleton woman.
Once a HOM gestation has been diagnosed by ultrasound,
the couple is vulnerable. They did not expect to have so many
embryos successfully growing, and they are certainly overwhelmed by this reality. Frequently, the reproductive endocrinologist will suggest multi-fetal pregnancy reduction of
one or more embryos to leave twins. Although multi-fetal
pregnancy reduction is certainly an option, there also needs
to be a balanced discussion about carrying the HOM gestation, including outcome data for mortality and morbidity.
Prompt consultation with a perinatologist who has experi-
ence in caring for HOM pregnancies is important. The couple
needs to get as much information as possible to make an
informed decision for their circumstances. After considering
the medical/obstetric/neonatal risks and the psychosocial/
economic impact on their family, each couple must decide on
multi-fetal pregnancy reduction or carrying their HOM gestation. A perinatologist should be managing these very challenging pregnancies.
At the first prenatal visit, there are a number of important
assessments and management interventions that are initiated.
Ultrasound assessment is important to determine placentation because obstetric complications and management will
differ based on the nature of the placentas and sacs. Signs of
dichorionicity include separate placentas, fetuses of different
gender, ”thick“ membrane, and ”twin peak“ or lambda sign.12
The twin peak sign is an ultrasound finding of a triangular
projection of placental tissue between the layers of dividing
membrane at the junction of the two placentas. Early ultrasound evaluation correctly identifies placentation in over
90% of multiple gestations. If placentation cannot be clearly
established, the assumption should be made that it is monochorionic and the pregnancy managed by default as being at
risk for TTTS. The rare occurrence of monochorionic/monoamniotic placentation adds increased risk of fetal death from
cord entanglement to the risks of HOM gestation. Assessment
of the uterus for the location of the lowest placenta is important. Despite the presence of three, four, or five placentas,
Francois and coworkers13 demonstrated no statistical difference in the incidence of placenta previa in singleton (55/
29,268; 0.19%), twins (3/766; 0.46%), or triplets and quadruplets (1/140; 0.71%).
Other assessments and interventions would include cigarette smoking, alcohol or recreational drug usage, and prescription medications that should be avoided in pregnancy
(eg, ACE inhibitors). Other areas of inquiry include questions
regarding domestic violence, which may involve up to 8% of
pregnant women and age-related risk of chromosomal abnormalities. Biochemical assessment of genetic risk is not
available for triplets or quads. First trimester nuchal translucency measurements will not differ from singleton assessment and prenatal invasive testing offered for fetuses with
abnormal measurements. Second trimester genetic ultrasound assessment for “minor markers” associated with aneuploidy may also allow selective sampling of individual fetuses
if invasive procedures [chorionic villus sampling (CVS) or
amniocentesis] are to be avoided. The risk of three or four
amniocenteses is not currently known, but twin amniocenTable 2 Approximate Gestational Age at Delivery
No. of Live Born Babies
Mean Gest. Age
at Delivery
Singleton
Twins (Spontaneous)
Twins (Reduced)
Triplet
Quadruplets
Quintuplets
40 weeks
36-1/2 weeks
35-1/2 weeks
33 weeks
29-1/2 weeks
29 weeks
High-order multiple gestations
tesis may be associated with a greater than 1% risk of miscarriage.
HOM gestations need to be assessed for stress factors in the
patient’s life, including heavy work, prolonged standing,
high emotional or intellectual stress, heavy lifting or straining, or perhaps caring for one or two young children in the
home. As these activities often precede preterm labor, it is
important to reduce or eliminate the majority of them wherever possible. In addition, the mother should eliminate activities that cause fatigue, minimize standing, lifting, and bending, and plan increased periods of rest. Because the commute
to/from work may be stressful, working at home may help if
that is possible. Sexual activity is permissible up to 20 weeks,
and beyond, if the couple desires to continue. However, the
male ejaculate contains prostaglandin compounds that may
initiate contractions, so it is wise to use a condom after 20
weeks to reduce any possible stimulation of contractions.
The next aspect of information-sharing involves a discussion of the physiologic and psychologic stresses of a HOM
pregnancy. Every organ system in the mother’s body will be
affected by the physiologic changes of her special pregnancy.
She may already be experiencing nausea and vomiting (frequently encountered in multiple gestations). Uterine distention occurs early and becomes extreme beyond 30 weeks.
Backache, pressure, heartburn, constipation, hemorrhoids,
headaches, leg cramps, constant fetal movement, pelvic pressure, and urinary frequency often make the mother miserable. Psychologic stresses will also take their toll on the
mother, as well as her partner and children, if any are in the
home. Anxiety about the risk to her babies, guilt about not
carrying her share of the household chores (other children,
cleaning, cooking, washing, working), depression, sleep deprivation, and physical stresses are all extreme in HOM gestations. These eventualities must be discussed with the patient early on so that preparation can be made to minimize
their effects. The ability to discuss their feelings with others
who have experienced a HOM pregnancy is extremely important. There are two large support groups for multiple
gestations. Mothers of Supertwins (MOST) can be reached at
[email protected], phone (631) 859-1110; and The Triplet Connection can be contacted at www.tripletconnection.
org, phone (435) 851-1105.
The next part of the first prenatal visit should shift to
describing the proactive approach that the physician will take
to give the patient the best possible chance for a good outcome. It is not appropriate to be passive in caring for a triplet
or quadruplet gestation. The most important and frequent
risks include: preterm labor which occurs in 76% to 90% of
HOM gestations,14,15 pregnancy-induced hypertension (PIH)
in 35% of triplets15 and 72% of quadruplets,15 preterm premature rupture of the membranes (PPROM) in 20%,14,15 anemia in 25%,14,15 gestational diabetes (7% in triplets, 19% in
quads),14,15 and incompetent cervix in 14%.15 Small for gestational age (birth weight ⬍10th centile for a singleton gestation) and intrauterine growth restriction (IUGR) (birth
weight ⬍3rd centile for a singleton gestation) occur, respectively, in about 20% and 9% of triplets14 and 10% and 1% of
quads.15 Our proactive approach includes aggressive weight
307
gain, modified bed-rest at 20 weeks (which usually means
stopping work), cervical length assessment every 1 to 2
weeks from 18 to 24 weeks, fetal fibronectin testing (fFN)
starting at 24 weeks, home uterine activity monitoring
(HUAM) at 20 weeks, office visits every 1 to 2 weeks, monitoring for PIH, ultrasound follow-up of fetal growth, and
biophysical profile (BPP) assessment of fetal acid-base status.
The purpose of each of these interventions is explained to the
patient initially and then re-explained in detail when they are
instituted.
Certain medications are prescribed routinely in our practice. Prenatal vitamins once a day and folic acid 1 mg/d are
continued from preconception. Ferrous sulfate 325 mg/d is
started after the first trimester. Baby aspirin 81 mg/d and
calcium supplementation 2000 mg/d (four Tums® have 2000
mg of calcium) are started at about week 15, as they may
lessen the risk of PIH developing. Colace is started at 100 mg
(once or twice a day) for stool softening. We also recommend
magnesium supplementation at 1.2 g/d and zinc supplementation at 45 mg/d, as preterm labor is associated with a low
serum magnesium level and zinc levels may be related to
PPROM.
At 18 weeks, the patient should have a targeted ultrasound
examination to assess carefully the anatomy of each fetus to
determine whether any identifiable malformations exist that
may present special needs for intervention, either in utero or
in the NICU. Careful attention should also be paid to the
cervix. A vaginal ultrasound examination should be performed to assess cervical length and any evidence of funneling. Even nulliparous patients with a HOM gestation are at
risk of a functionally incompetent cervix. This is probably
due to increased levels of relaxin, a hormone that causes
softening and dilation of the cervix,16 as well as downward
pressure from the expanding uterine contents. The two circumstances producing the highest levels of relaxin in pregnancy are multifetal pregnancy and ovarian stimulation to
cause multiple follicles to mature. Such infertility manipulations are frequent in HOM gestations. Follow-up cervical
length ultrasound examinations should be done every 2
weeks (between 18 and 24 weeks) if cervical length is greater
than 3 cm, or more frequently if it is less than 3 cm. Cervical
shortening should prompt careful assessment for uterine
contractions. If contractions are documented, treatment
should be initiated with tocolytic drugs, preferably with a
terbutaline pump for continuous parenteral administration
of the drug.17 If uterine activity is not occurring, strong consideration should be given to cervical cerclage.
Further ultrasound assessments are routinely indicated for
fetal growth every 3 to 4 weeks. Routine assessment of fetal
well-being in all HOM pregnancies is indicated beginning at
the 32nd week. It is difficult at best and often impossible to
use electronic FHR monitoring to assess fetal status, so BPP
testing is equally appropriate. Elliott and Finberg reported on
the utility of BPP testing in HOM pregnancies, and recommended routine testing twice a week starting at 32 weeks for
normally progressing pregnancies.18 BPP should be started
earlier if there is a small-for-gestational age fetus or if PIH is
diagnosed.
308
It is important to note that abnormal placentation affects
the need for ultrasound assessment in multiple gestation,
including HOM pregnancies. In particular, monochorionic
twins, or less commonly, monochorionic triplets, are at risk
of developing acute, severe TTTS.19 This complication occurs
most frequently in the second trimester when discordant fetal
size and extremes of amniotic fluid volume (polyhydramnios
in the recipient sac and oligohydramnios in the donor sac)
can develop very quickly (10 days to 2 weeks).20 Making the
diagnosis in a timely manner allows appropriate intervention
to be initiated. Two treatments that have improved outcome
in TTTS include aggressive therapeutic amniocentesis20 and
laser ablation of anastomotic vessels on the chorionic plate.21
It is important that fetal size and amniotic fluid volume be
assessed every 2 weeks from 16 to 26 weeks in pregnancies
containing one or more monochorionic placentas.
Office visits should be every 2 weeks after 18 weeks. At
ⱖ20 weeks, a digital cervical examination is added at each
visit to assess for cervical dilation, which is sometimes difficult to assess with ultrasound. The patient is also asked about
signs/symptoms of preterm labor. These would include:
cramping, pelvic pressure, backache, contractions, change in
vaginal discharge, pressure sensation in the inner thighs, or a
feeling that things are just not right.
The benefit of bed-rest is very difficult to establish. Goldenberg and colleagues reviewed the literature and concluded
that bed-rest is of no benefit in any obstetric circumstance.22
It is my belief that, whereas bed-rest alone will not prevent
preterm delivery, it may decrease the frequency of uterine
contractions. It is widely appreciated that the more contractions that are occurring the greater the possibility that preterm labor (PTL) will occur. Garite and coworkers demonstrated an increase in contractions 48 hours before PTL to a
mean of 3.5/h, and further to 5.5/h in the 24 hours before the
onset of PTL.23 In our patients with HOM gestations, administration of betamethasone caused PTL in those patients
whose background uterine activity was ⱖ3.5 contractions/
hour, although it did not initiate PTL if the contractions were
less than 3.5/hour when the steroids were given.24 We believe
that 3.5 contractions/hour represents a threshold value that
increases the likelihood of PTL. In our practice, modified
bed-rest is prescribed to lower the background contraction
frequency to reduce the likelihood of PTL. Modified bed-rest
includes time spent recumbent in bed, on a couch, on a
recliner chair, or outdoors in a chaise-lounge. The patient can
go to the bathroom ad libitum and shower once a day. Mild
ambulation for 15 to 30 minutes can be added for individual
patients. Tocolysis may also be needed to keep the background contractions fewer than 3.5/hour.17
The role of contraction monitoring in the management of
patients at risk of PTL remains controversial. In theory, detection of uterine contractions is important in attempting to
detect PTL early. If a patient calls her physician with a complaint of cramping or contractions, the initial evaluation includes placing the patient on a contraction monitor in the
hospital. However, the use of a more sensitive tocodynamometer in the outpatient setting evokes intense feelings in
practitioners about the clinical utility of the same technology
J.P. Elliott
that is used in the hospital. In either event, the monitor will
not prevent PTD, whereas it might allow detection of PTL at
an earlier stage to allow appropriate intervention possibly to
prevent PTD.25 The vast majority of articles evaluating home
uterine activity monitoring (HUAM) support the concept that
daily interaction with the patient by a specially trained nurse
with or without a tocodynamometer affords better outcomes
than typical standard management with weekly office evaluations.26 Dyson and coworkers27 later reported no difference
in twins followed by weekly nursing contact, daily nursing
contact, or HUAM.
In HOM gestations, it is important to keep background
uterine contractions to ⱕ3.5/h. The HUAM can be utilized to
assess this background activity, in addition to picking up
active PTL in a more timely manner. Outpatient management
of HOM gestations is not only appropriate but is psychologically beneficial for the patient and her family.28-30
Fetal fibronectin testing is a useful laboratory test to predict risk of PTD in patients at risk. In singleton pregnancies at
risk of PTD, Peaceman and colleagues demonstrated a PTD
rate of ⬍1% within 2 weeks of a negative fFN test.31 This is
very reassuring. A positive fFN is associated with approximately a 17% risk of PTD in the next 2 weeks. The significance of fFN in HOM gestations is less well understood. In
unpublished data for our practice, a negative fFN in a HOM
gestation is associated with a 6% risk of PTD in the next 2
weeks, whereas a positive test has almost a 50% risk of delivery over the same period. A positive fFN should prompt
closer monitoring of contractions, steroid administration if
that has not yet been given, and weekly office visits. Aggressive tocolysis should be initiated when labor occurs.
Another routine recommendation in our practice is the use
of hydrotherapy. The patient is encouraged to stand in a
swimming pool (if available) for 20 to 30 minutes a day. A spa
or Jacuzzi is also appropriate, with the legs as deep as possible. The water is very soothing both physically and psychologically, especially as the mother gets into the third trimester. The physiologic benefits of hydrotherapy include a
beneficial effect on peripheral edema, which occurs in almost
all HOM gestations. Head-out immersion is useful in increasing the intravascular volume, which in turn increases blood
flow to the placentas. Strong32 reported an increase in amniotic fluid volume in placental insufficiency in five patients
utilizing this therapy.
Although I believe that prevention of PTL should be the
goal of management, there will be patients who develop PTL.
PTL in a multiple gestation is very difficult to control with
tocolytic drugs once it has started. The increased renal clearance of drugs in multiple gestations due to increased blood
flow to the kidneys necessitates increased dose of tocolytic
drugs in acute PTL. Elliott and Radin33 published data showing that higher doses of MgSO4 had to be administered to
achieve therapeutic serum levels in HOM gestations compared with singleton pregnancy. It is important to remember
that therapeutic serum levels are necessary for the tocolytic
drug to be successful. Frequently, too little drug is administered to achieve a therapeutic effect, and when contractions
do not stop, the drug is declared a failure and discontinued
High-order multiple gestations
309
when really the dosage only needed to be increased to treat
the patient successfully. A prospective study by Cox and
coworkers34 illustrates the danger of giving too little drug and
then declaring that the drug is ineffective at preventing PTD.
In our experience acute tocolysis in multiple gestations
frequently requires not only higher dosages but also multiple
drugs (MgSO4, terbutaline, and indomethacin). I limit intravenous fluids to reduce the risk of pulmonary edema, but am
aggressive with all these drugs. The initial bolus of MgSO4 is
6 g and then 3 g/h infusion. I occasionally increase it to as
much as 6 g/h infusion, if necessary, monitoring magnesium
levels to maintain a serum level of 8.5 mg/dL in resistant
cases.33 Serum Mg levels can be checked if tocolysis is not
achieved to determine whether an increase in the dosage
being administered is warranted or if the patient is excessively symptomatic to determine whether the MgSO4 infusion can be reduced. Routine serum Mg determinations are
seldom necessary but can be obtained every 6 hours. Subcutaneous terbutaline can be used as intermittent injection dosing (0.25 mg) or with continuous infusion of a basal rate and
programmed periodic boluses by infusion pump. Indomethacin (100-mg suppositories, every 6 hours ⫻ 6 to 8 doses)
can be added, or alternatively, ibuprofen 600 mg every 6
hours may be used. After 48 to 72 hours with the contractions spaced out to three to five per hour, the patient can be
converted to a terbutaline pump. Oral maintenance tocolysis
is generally ineffective, especially in multiple gestations because of the enhanced renal clearance of the drug. Extended
tocolysis with continuous intravenous MgSO4 or terbutaline
pump17 is more effective in maintaining the pregnancy than
oral agents, especially when the cervix is dilated greater than
or equal to 2 cm or the station is ⫺1 or lower. Both MgSO4
and terbutaline pumps can be used for months with minimal
side effects, but the former is used inpatient, whereas the
latter may be used in the home. The side effects of MgSO4
Table 3 Maternal Morbidity and Obstetrical Complications of
Quadruplet Pregnancy
Variable
Incidence (%)
Antepartum hospitalization
Hyperemesis gravidarum
Hyperemesis gravidarum, TPN required
Gestational diabetes mellitus A1
Gestational diabetes mellitus A2
Anemia (Hct <30%), no antepartum
transfusion required
Anemia (Hct <30%), antepartum
transfusion required
Antepartum bleeding
Placenta previa
Pre-eclampsia
HELLP syndrome
Preterm premature rupture of the
membranes
Preterm labor
Twin-to-twin transfusion syndrome
Chorioamnionitis
100
9.4
3.1
18.8
3.1
Data from Francois and colleagues.40
25
15.6
3.1
0
71.9
12.5
18.8
90.6
3.1
6.3
Table 4 Neonatal Outcomes of Quadruplet Pregnancy
Variable
Incidence (%)
Intrauterine growth restriction
Small for gestational age
Chromosomal abnormalities
Congenital malformations
Respiratory distress syndrome
Transient tachypnea of the newborn
Apnea
Suspected or culture-proven sepsis
Necrotizing enterocolitis
Intraventricular hemorrhage, grades III/IV
Periventricular leukomalacia
Gastroesophageal reflux
Retinopathy of prematurity
Neonatal seizures
Pulmonary hypertension
Neonatal death
0.8
10
0
1.7
32.5
12.5
1.7
7.5
1.7
0
0.8
12.5
6.6
0.8
1.6
0.8
Data from Francois and colleagues.40
include headache, chest pressure, warm flushed feeling, nausea, double vision, and muscle weakness. These all disappear
at 72 to 96 hours of therapy. Extended home management on
terbutaline pump therapy is appropriate in many circumstances.17
There is absolutely no evidence that tocolytic drugs lose
their efficacy at 48 hours. Physicians have a tendency to
decrease drug therapy too soon when the PTL has not resolved, when one should use the drugs aggressively and appropriately to achieve the desired effect. The most feared
complication of tocolytic therapy is pulmonary edema. Pulmonary edema is not caused by the MgSO4, but is related
instead to associated cardiovascular stresses. In unpublished
data from our practice, every patient who developed pulmonary edema had one or more of the following cardiovascular
stressors: fluid overload, hypertension, infection, multiple
gestation, or anemia. If pulmonary edema develops, one
should decrease the dose of MgSO4 and treat with oxygen and
furosemide for diuresis. The drug does not need to be discontinued. The incidence of pulmonary edema is 3% to 5%
in multiple gestations on MgSO4. Complications of terbutaline pump therapy are very rare. Elliott and coworkers35 documented mild transient side effects (tremors, SOB, or chest
discomfort) in 15.5% and serious cardiovascular complications in 12 (0.1%) of 9359 patients treated with terbutaline
pump therapy, with 9 of the 12 being pulmonary edema.
Tocolytics are safe and effective when used by experienced
physicians and nurses.
PIH is frequent in HOM gestations, and often HELLP syndrome is present. We will aggressively use dexamethasone to
treat HELLP syndrome when it develops in our HOM pregnancies. We use a dosage regimen of 2 mg of dexamethasone
IV q6 hours ⫻ 2 days; 2 mg IV q8 hours ⫻ 2 days, and then
2 mg q12 hours until delivery. Heller and Elliott36 reported
the successful use of steroids to treat HELLP syndrome in
these circumstances. Although the therapy is not 100% successful, days to many weeks can be gained using this treat-
J.P. Elliott
310
ment, and any gestational gain affects three or four babies,
emphasizing the importance of any lengthening of gestation.
Delivery represents the final obstetrical report card for an
HOM gestation. We deliver our HOM pregnancies by way of
cesarean section, as has been documented to occur in over
90% of patients with triplets.37 Although vaginal delivery is
not inherently a more risky alternative, cord prolapse and
placental abruption may complicate attempted vaginal delivery. Our goal is an elective delivery. We choose 35-0/7 weeks
for delivery of triplets and 34-0/7 weeks for quadruplets and
quintuplets. The reason for this is respect for the physical and
psychologic well-being of the mother and the excellent neonatal outcome of babies born at that gestational age, although
we do not advocate elective earlier delivery of HOM gestations or other pregnancies solely because of overall excellent
neonatal outcome. In general, it is not appropriate to deliver
a patient unless the dangers of leaving the patient pregnant
exceed the risk to the fetus in the nursery. A delivery at 36
weeks is better for a baby than a delivery at 35 or 34 or 33
weeks.36 In our quadruplets, elective delivery occurred in
22.7% of our patients, which was second to PIH (40.3%) as
the reason for delivery.38
In the last 20 years, we have cared for over 500 triplet
pregnancies, over 75 quadruplets, and 6 quintuplets. Francois and colleagues15,38-40 reported our outcome with 32 nonconsecutive quadruplet pregnancies. These were chosen because they were the patients that we were able to get the
medical records of mother and all 4 babies in time to submit
an abstract to the Society of Maternal Fetal Medicine meeting.
Maternal morbidity is given in Table 3, and neonatal outcome
is presented in Table 4. The mean gestation age at delivery
was 32.1 weeks (⫾2.1 weeks) with a range of 26.7 to 34.1
weeks. Six pregnancies (20%) were delivered between 30
and 32 weeks, and 18 (60%) were delivered between 33 and
34 weeks. There was 1 death in these 120 babies, for a perinatal mortality rate of 8.3/1000. Major neonatal morbidity
was rare, with necrotizing enterocolitis in 1.7%, intraventricular hemorrhage (grade III or IV) in 0%, periventricular leukomalacia in 0.8%, and retinopathy of prematurity (grade II
to III) in 6.6%. This low rate of morbidity certainly reflects
the large number of babies born after 32 weeks. Garite and
colleagues3 have provided data that document that the outcome of babies in a multiple gestation is similar to singletons
born prematurely at each week after viability. Thus, it is clear
that delivery at a more advanced gestational age is the key to
successful pregnancy outcome in multiple gestation. Poor
outcome in HOM gestation is a possible result, but it is not
even a common result with our approach to management.
Conclusion
This article provides an overview of HOM gestation and our
suggestions for management. Based on our outcomes, we
advocate an aggressive approach to HOM pregnancy management. Adequate weight gain will help reduce the incidence of low birth weight and IUGR fetuses. Aggressive manipulation of background uterine contractions with bed rest,
psychologic reassurance, and tocolysis with a terbutaline
pump will decrease the incidence of true PTL, and aggressive
tocolysis with MgSo4 and other drugs will decrease PTD.
Treatment of HELLP syndrome with dexamethasone will
prolong pregnancy in those patients developing PIH/HELLP.
Management is directed at delaying delivery until 34 to 35
weeks if at all possible.
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