MULTIPLE PREGNANCY doc

Two independent mechanisms may lead to multiple gestation: segmentation of a single fertile ovum identical, monovu-lar, or monozygotic or fertilization of separate ova by different sperm

DEFINITIONS, ASSOCIATION, INCIDENCES AND IMPORTANCE

Multiple pregnancy involves more than one embryo (fetus) in any one gestation Two independent mechanisms may lead to multiple

gestation: segmentation of a single fertile ovum (identical, monovu-lar, or monozygotic) or fertilization of separate ova by different

spermatozoa (fraternal or dizygotic) multiple pregnancy.

In the development of twins (the most frequent higher-order

ges-tation), monozygotism is constant ( ⬃2.3–4/1000 deliveries), whereas

dizygotism has certain predispositions Dizygotic twinning is

inher-ited as a recessive autosomal trait via the female descendants The

father’s being a twin has little influence on the rate of twinning in

his offspring Race is of special importance: blacks have the

great-est incidence of dizygotic twins (about 50/1000 births in Wgreat-estern Nigeria), whites are intermediate, and Asians have the fewest (⬃1–2/1000 births in Japan) Other factors influencing dizygotism

include greater maternal height or weight, increasing maternal age (peaks at 35–45 years), and white mothers of blood group O or A

In developed countries, two of the major causes of multiple gestation

are cessation of oral contraception and artificial ovulation

induc-tion The latter is of particular concern for higher-order multiple

gestations (triplets and above) are increasingly common (1.2- to 2-fold increase in developed countries) as a result of assisted re-productive technologies (ART) Although these pregnancies are not

at significantly increased risk from the ART, they are at exceptional

risk for immature or premature delivery and other morbidity and mortality associated with higher-order multiple gestations.

In the heterogeneous population of the United States, slightly 30% of twins are monozygotic, and nearly 70% are dizygotic

(Fig 12-1) In such a population, a useful estimate of the natural

fre-quency of multiple gestation is that twinning occurs ⬃12 per 1000

births (1:88) Each increase in birth number may then be estimated

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MULTIPLE PREGNANCY

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by raising the ratio 1:88 to the exponential of the birth number mi-nus 1 For example, triplets occur 1:88(31 2) 1:7744; quadru-plets occur 1:8833 1:681,472

In multiple births, males predominate (but more die early) About 75% of twins are of the same gender Both are males in ⬃45% of cases, and both are females in ⬃30%

Maternal morbidity and mortality are much higher in multiple than in singleton pregnancy There is increased frequency and

sever-ity of anemia; increased occurrence of urinary tract infection; more

preeclampsia-eclampsia, hydramnios, and uterine inertia

(overdis-tention); and a greater chance of hemorrhage (before, during, and

after delivery)

The perinatal mortality rate of twins is 4–6 times higher—and for triplets much higher again—than for singletons because of prematu-rity and associated difficulties Indeed, as the number of fetuses rises,

their average size and length of gestation decrease Twins are deliv-ered, on average, at ⬃36 weeks, triplets at ⬃32 weeks, and quadru-plets at 30 weeks Moreover, intrauterine growth retardation

(IUGR) is more common in all multiple gestations (as opposed to

sin-gletons) Congenital abnormalities of all organ systems are as high as

18% among twins (considering both monozygotic and dizygotic)

Other perinatal risks of multiple gestations include abnormal

presen-tation and position, hydramnios, hypoxia because of cord prolapse

(⬃4%, 5 times more common in multiple pregnancy), placenta

pre-via, and premature separation of the placenta after the first twin or

operative manipulation Collision, impaction, and interlocking of twins

are additional critical but uncommon complications (Figs 12-2, 12-3, and 12-4) Because of maternal and perinatal risk, many authorities

FIGURE 12-1. Placental variations in twinning (After Potter.)

recommend that no less than qualified obstetricians care for twins and that maternal–fetal consultation be utilized Additionally, triplet and higher birth order risk is such that maternal–fetal specialists should be involved in, or provide their care

FIGURE 12-2. Locked twins.

Monozygotic multiple fetuses are far more likely to be jeopard-ized than dizygotic twins For example, monozygotic twins have

3 times the incidence of serious congenital abnormalities compared

to double-ovum twins Conjoined twins and enhanced early loss of one or both fetuses (probably two thirds of all implanted multiple gestations) result in a single birth Moreover, a parasitic fetus with-out a heart (fetus acardiacus, complicating ⬃1%) is also a potential problem of monozygous twinning Other unique monozygotic com-plications include placental vascular shunts resulting in the twin-to-twin transfusion syndrome (to some degree complicates 5–35%), in which the smaller but cardiomegalic twin pumps its arterial blood into the lower pressure venous system of the larger, plethoric, and macrosomic twin Cord abnormalities, more common in monozy-gous twins, include two-vessel cords and velamentous cord inser-tion (7% incidence) Cord entanglement in a single monoamniotic sac may occur, and this leads to a ⬃50% loss Monozygotic twins are smaller and are more likely to die in utero than dizygotic twins This may be because a single (monochorionic) placenta is less ef-ficient than a fused dichorionic placenta

The time of segmentation is crucial to the outcome of monozy-gotic fetuses Division before the morula and differentiation of the

FIGURE 12-4. One vertex and one breech presentation.

FIGURE 12-5. Amniotic membranes of twins.

trophoblast (day 5) lead to separate or fused placentas with two chorions and two amnions Division after trophoblastic differentia-tion but before amnion formadifferentia-tion (5–10 days) is the pattern of two thirds of all monozygotic twins This results in a single pla-centa, a common chorion, and two amnions Division after amnion differentiation (10–14 days) leads to a single placenta with one chorion and one amnion Division
14 days results in incomplete twinning Division just before that (8–14 days) may lead to con-joined (Siamese) twinning

Monozygotic multiple gestations share the same genetic features (e.g., blood group, histocompatibility, and basic karyotypes) There-fore, skin grafting and organ transplantation are possible and be-come the ultimate test of monozygotic vs dizygotic twinning Monozygotic twins are termed identical, but they often have con-siderable phenotypic variation Dizygotic (fraternal) twins may be

of the same or different genders and bear only the resemblance of brothers or sisters They may or may not have sufficiently similar genetic features to serve as organ donors for each other

Examination of the placenta and membranes assists in zygosity determination At delivery, careful inspection and dissection of the

placenta(s) and membranes, particularly the membraneous T-septum

or dividing membrane between the twins, may reveal microscopic evidence of the probable type of twinning Monozygotic twins have

a thin septum made up of two amniotic membranes only (no chorion and no decidua) Indeed, ⬃1% of monozygotic twins are monoam-niotic By contrast, dizygotic twins have a thick septum composed

of two chorions, two amnions, and intervening decidua (Fig 12-5)

In some circumstances, it is necessary to resort to definitive genetic testing to determine monozygosity or dizygosity The early diagno-sis of twins is mandatory, and assessment of the placenta is the key

CLINICAL FINDINGS

The clinical suggestions of multiple pregnancy include the following:

● A uterus larger than expected for the duration of pregnancy (
4 cm than anticipated);

● Excessive maternal weight gain not explained by eating or edema;

● Hydramnios;

● Iron deficiency anemia;

● Maternal reports of increased fetal activity;

● Eclampsia-preeclampsia;

● Uterus containing 3 large parts or multiple small parts;

● and simultaneous auscultation or recording of two fetal hearts varying
8 beats per min and asychronous to the maternal heart

LABORATORY FINDINGS

Commonly encountered laboratory findings in multiple pregnancy

include: abnormal elevation of maternal hCG and/or

alpha-fetoprotein, moderate reduction in Hct (also Hgb and RBC count, i.e., iron deficiency anemia), blood volume increased over normal pregnancy values, and an increased incidence of glucose intoler-ance Cervicovaginal secretion of fetal fibronectin (Ffn) is a sensi-tive predictor of preterm delivery in twins, but has low specificity Thus, Ffn is best used in conjunction with other criteria (e.g., sono-graphic evaluation of cervical length) Currently, there is little Ffn data for higher-order multiples

SONOGRAPHY

Sonography is vital in modern management of multiple gestations.

Areas of utility include: assisting in zygosity determination, detect-ing and assessdetect-ing fetal anomalies, determination of growth, assess-ing amniotic fluid, determinassess-ing well beassess-ing, management of

antena-tal testing, and caring for uncommon complications Therefore, a

standardized approach to sonographic evaluations is useful EARLY SONOGRAPHY

Sonography (no later than the early second trimester) assists in de-termination of chorionicity Multiple pregnancy may be demon-strated by vaginal ultrasonography before 6 weeks, and multiple pregnancy should be routinely detected by other scanning methods

at8 weeks A pitfall of multiple gestation sonography, particu-larly those done at 6 weeks, is both undercounting and over-counting fetuses

Sonographic visualization of the chorion(s) can be assessed as early as 6–7 weeks (after LMP), with dichorionic being visualized earlier Although reliable imaging of the amnion is not usually pos-sible before the 9–10th week This determination is important be-cause of the disproportionate outcomes related to chorionicity and amnionicity Differential findings include: placental masses, septal thickness, “twin peak” sign, as well as fetal gender

At 16–20 weeks, a detailed sonographic anatomic survey screens for congenital anomalies and provides a baseline for further testing

Serial sonographic examinations may vary by chorionicity Sonography for dichorionic pregnancies are often started later (26 weeks v 23 weeks) and subsequently, performed less frequently (4 weeks v 3 weeks) than monochorionic twins, although optimal schedules have not been articulated Serial examinations are useful

in determination of growth patterns, assessing amount of amniotic fluid, determining fetal position, ascertaining placental maturation, and a host of other useful information

Serial songraphic assessment of cervical length as well as screening for cervical funneling is a useful adjunct in management

of multiple gestations Premature cervical shortening and cervical funneling both indicate the potential for premature labor and de-livery

Prior to or at the onset of labor, sonography is useful in plan-ning management (see the discussion that follows)

DIFFERENTIAL DIAGNOSIS

Single large pregnancy, hydramnios, hydatidiform mole, abdominal

or pelvic tumors complicating singleton pregnancy, and compli-cated multiple gestation (e.g., triplets) must all be considered in the diagnosis of multiple gestation.

TREATMENT PREVENTION OF

MULTIPLE PREGNANCY

Currently there are few possibilities for preventing multiple

gesta-tion, but those known follow Use of a barrier type of contracep-tion for the first cycle off oral contraceptives may prevent fertil-ization of multiple ova Administering clomiphere initially, if ovulation is to be induced results in fewer multiple gestations How-ever, dizygous twins still occur in 5%–10% of clomiphene-stimu-lated cycles Avoiding the use of human menopausal gonadotropin therapy unless the proper dosage can be established and daily sonog-raphy is available for ovulation monitoring assists in lowering mul-tiple gestation Selective reduction of fetuses (i.e., selective elimi-nation) is a new and controversial technique of elimination of one

or more fetuses This technique employs ultrasonic-guided methods for reducing the number of fetuses, with the rationale that intact survival of a few is better than nonintact survival of many Initial reports support this approach in selected cases

AVOIDING MATERNAL

COMPLICATIONS

IN MULTIPLE PREGNANCY

A thoughtful approach is necessary for the mother with multiple

gestations This plan begins with early diagnosis of multiple

preg-nancy This goal may be achieved by obtaining sonography (ideally

on all and certainly on questionable pregnancies) no later than 12–16

weeks A high-protein, high-vitamin diet; with no limitation of

weight gain assists in prevention of fetal intrauterine growth retar-dation Dietary supplements demonstrated to be useful in multiple

gestations include: a prenatal vitamin per day, folic acid of 1.0 mg

per fetus per day, supplemental iron preparations as indicated by

hemogram and calcium to a total intake of 1500 mg/day

benefi-cially influences birth weight

Because of the number of potential problems, it is common to

examine the patient with multiple pregnancy more often than most

during pregnancy (individualized, but in most cases at least twice

as often) Physical activity is usually limited to ensure adequate

uter-ine blood flow (e.g., cancel regular exercise programs) Frequent rest periods are initiated after the 24th week (e.g., 1 week of bedrest

at 26 weeks and again at 32–33 weeks) Ultrasound examinations and blood counts are obtained more frequently Ultrasound

exami-nations for growth progress may be useful monthly from diagnosis until the 32nd week, when both ultrasonography and BPP on each fetus may be useful on a weekly basis Cervical length sonography may be performed as often as every other week in the latter half of pregnancy

Given the risk, consideration is given to deliver all patients with

multiple pregnancy in a tertiary medical facility if possible

Psy-choprophylaxis is often stressed, and the patient introduced to a sup-port group Additionally, patients find literature concerning multi-ple gestation and preterm birth prevention education helpful At the

time of delivery, increased blood loss may be anticipated

(hemor-rhage is 5 times increased over singletons) Thus, seeking donors acceptable to the patient in advance may be worthwhile In cases where one fetus delivers untenably early (e.g., 22 weeks), some now

recommend delaying delivery of the remaining fetuses (especially

if membranes are intact) in an attempt to decrease morbidity and mortality in the remaining fetuses Although the delayed delivery

of remaining fetuses improves prognosis, there is no consensus re-garding technique or enough cases to demonstrate true statistical relevance In sum, care of the mother with a multiple pregnancy re-quires enhanced sensitivity to, as well as frequent assessment of, maternal symptoms and cervical status

PREVENTION OF FETAL

COMPLICATIONS OF

MULTIPLE GESTATION

Details concerning identifying congenital anomalies are noted pre-viously (see “Imaging”), as are techniques to maximize fetal growth (see “Maternal Care”) Preventing early preterm delivery is an

ob-jective best realized through maximizing maternal antenatal care

(as above) The utilization of fetal fibronectin screening may be use-ful in detection of preterm labor Utilization of home uterine activ-ity monitoring, salivary estriols, and other modalities may be con-sidered Cervical cerclage may delay preterm birth in selected cases Indeed, some now recommend this in triplet and higher-order ges-tations Further study is necessary, however, prior to recommend-ing this approach

Tocolytic drugs to prevent early birth may be effective

(Chap-ter 11); however, these agents must be used with great care in

mul-tiple gestation because of possible maternal pulmonary edema

Ap-propriate fetal therapy is initiated if early delivery is anticipated (Chapter 11)

ASCERTAIN FETAL PROBLEMS

It is important to ascertain fetal problems early Certainly, some of

these may be determined by repeated sonography to screen for fe-tal defects, IUGR, fetus-to-fetus transfusion syndrome, and fefe-tal well-being Antenatal diagnosis is used as indicated The twin-to-twin transfusion syndrome is usually manifest in monozygous twin-to-twins

by discordant fetal growth (a difference of
20%) and one fetus having polyhydramnios while the other has oligohydramnios Indi-vidual testing for pulmonary maturity studies is utilized (if neces-sary) If selective reduction is an option, the patient may be referred

to an appropriate center

LABOR

During labor, special vigilance is warranted Labor is conducted

with full preparations for cesarean section, should the need arise This includes: starting IV lactated Ringer’s solution with a large-bore needle, obtaining a complete blood count, and blood type and crossmatch for a minimum of 2 units packed red blood cells or whole blood Maternal and fetal oxygenation is enhanced by mask

or nasal prong oxygen therapy (7 liters/min) Sonography assists in ascertaining the fetal presentations In practice, this nearly always