بسم الله الرحمن الرحیم In the name of God

Multiple Gestation RAZIEH D.FIROUZABADI (MD) FELLOWSHIP IN ART RAZIEH D.FIROUZABADI (MD) FELLOWSHIP IN ART SHAHID SADOUGHI UNIVERSITY OF MEDICAL SCIENCE

Multiple gestations have become one of the most common high-risk conditions

A- most common: -the number of twins delivered in the United States has risen over 80% - Twins now represent approximately 3% of all live birth -Triplets and higher-order births; * improbabilities according to the Hellin-Zeleny hypothesis * increased 470% over the same time period (triplets1 in every 500 deliveries)

B-high-risk condition : - perinatal morbidity and mortality -greater risk of dying before their first birthday -increased risk of long-term mental and physical handicaps -increased risk of growth restriction -other complications : higher rates of congenital anomaly, twin-to-twin transfusion, monoamnionicity, cord prolapse, placental abruption, placenta previa,intrapartum asphyxia birth trauma * higher health care costs *preterm *LBW

Epidemiology and Zygosity A-Monozygotic (MZ) twins : *both fetuses arise from single fertilized ova *both fetuses are genetically identical * random event *incidence :3 to 4 per 1,000 live birth *use of assisted reproductive technology (ART)

B-Dizygotic (DZ) twinning: *result from multiple ovulation with fertilization by separate sperm *incidence : variable *factors are known to affect the incidence: 1-personal or family history 2- delayed childbearing 3-use of ART 4-Maternal race 5-higher BMI 6-recent discontinuation of hormonal birth control agents

Placentation A-Dizygotic (DZ) twinning: * will always be diamniotic, dichorionic *Two complete placental units *membrane separating: four layers

B-Monozygotic (MZ) twins: *the placentation depends on the time at which twin division occurs: 0-3: two amnion and two chorion 3-8:diamniotic, monochorionic 8-13:monoamniotic, monochorionic >13:monochorionic, monoamniotic placentation + physical attachment of the fetuses

16-36% 60-70% 1%

determining zygosity of the infants *Examination of the placenta(s) and a detailed description of its dividing membrane A-there is no dividing membrane: monoamniotic, monochorionic B-there is dividing membrane microscopic appearance: 1-two layers: diamniotic, monochorionic 2-four layers : diamniotic, dichorionic IF apposite sex : DZ same sex : DZ OR MZ

Prenatal Diagnosis The risk of aneuploidy related to: *primary zygosity : - DZ twins each fetus has an independent risk for aneuploidy the aneuploidy risk is related to maternal age -MZ twins will have the same karyotype (with rare exception ) their aneuploidy risk also will be related to maternal age

*secondary the mode of conception ! The percentage of naturally conceived DZ twins will vary somewhat with maternal age and ethnicity in the United States: MZ DZ natural 33% 67% reproduction 7% 93%

the chance of having at least one affected live-born twin at term is twice the maternal age associated risk. risk of having at least one affected live-born twin at term is the same as her age-associated risk DZ Unfortunately, since her twins are MZ, this risk actually is the risk of both fetuses MZ

1-zygosity 2-screening *genetic analysis of both fetuses(ONLY) *noninvasive ultrasonic determination of chorionicity and fetal sex *Second-trimester multiple-marker screening: -unconjugated estriol -hCG -MSAFP *first-trimester serum screening: -free B- hCG -PAPP-A -nuchal translucency (NT) multiple-marker screening generally has been used in twin pregnancies, although with a decreased sensitivity for aneuploidy and a higher false- positive rate compared with its use in singletons

Maternal Complications Women who are pregnant with multiples are more likely to be hospitalized antenatally for both an increased frequency and severity of pregnancy-related complications *higher plurality and the more extreme maternal adaptation(majority of these complications) *maternal characteristics: -older maternal age - nulliparity -increased pregravid BMI -conception by ART

Maternal Complications 1-Cardiovascular Risks 2-Hematologic Abnormalities 3-Metabolic Disorders 4-Pregnancy-Induced Hypertension or Preeclampsia 5-Placental Abruption 6-Hydramnios 7-Urinary Tract Infection 8-Postpartum Hemorrhage

Cardiovascular Risks major physiologic changes significant expansion of the plasma volume and cardiac output adaptational value absence of underlying cardiac disease well tolerance However *the common use of tocolytic therapy: -pulmonary edema -myocardial ischemia -potentially lethal maternal tachyarrhythmias * the common iatrogenic fluid overload *the occasional infection all will generate significant additional cardiovascular demand risk of postpartum cardiomyopathy (especially among older gravidas with higher-order multiple) multiple pregnancy was an independent and significant risk factor for admission to an intensive care unit

Hematologic Abnormalities Increased red blood cell volume expansion is unable to keep pace with plasma volume expansion physiologic hemodilution Hb & Hct *first trimester decline beginning *second trimester reaching a nadir *third trimester gradually rising

Hematologic Abnormalities in either the first or third trimester; Hemoglobin levels < 11 g/dL serum ferritin < 12 mg/dL IDA to 36% of multiple gestations 21% two- to threefold higher than in singletons The average hemoglobin concentration for women pregnant with twins is 10 g/dL at 20 weeks gestation ! *consumption of heme-rich animal protein *60mg/d Fe *1mg/d folic acid

Metabolic Disorders Women who are pregnant with multiples have lower fasting and postprandial glucose levels, exaggerated insulin responses to eating, and higher levels of B2-hydroxybutyrate than women pregnant with singletons These differences suggest: more rapid depletion of glycogen stores metabolism of fat between meals and during an overnight

Metabolic Disorders several placental hormones(human placental lactogen) anti-insulin effects Gestational diabetes (a disorder of relative insulin deficiency) Multiples pregnancy placental mass increased two- to three fold among multiples premature labor -B2 adrenergic agents -corticosteroids insulin resistance and hyperglycemia

Pregnancy-Induced Hypertension or Preeclampsia *it is frequently encountered in multiple gestations: -singletons ……….7% -twins …………….14% -triplets …………..21% -quadruplets …….40% *twins to have a 4-fold higher risk of preeclampsia and a 14-fold higher risk if the woman is primigravid

Pregnancy-Induced Hypertension or Preeclampsia *preeclampsia frequently occurs( in multifetal gestations): -earlier -more severe -more atypical:Hypertension is not always the presenting sign, nor is proteinuria universally present The most common presentation among these higher-order multiples was laboratory abnormalities consistent with HELLP

Placental Abruption *Twin pregnancies have an approximately threefold increased risk of abruption *Abruption occurs most frequently in the third trimester and also is a significant risk immediately after vaginal delivery of the first infant *Conformational changes in the uterine shape that occur between deliveries can predispose to a sheering off of the attached placenta,

Hydramnios *Hydramnios occurs in 2% to 5% of twin gestations, and twins account for approximately 8% to 10% of all cases of hydramnios *Hydramnios may develop as a consequence of TTTS with the cotwin experiencing both growth restriction and oligohydramnio *The development of idiopathic acute hydramnios with maternal respiratory embarrassment also has been reported in multiples

Urinary Tract Infection *Women with multiples have a 1.4-fold increased risk of developing urinary tract infection during pregnancy *This complication is thoughtto be a consequence of increased urinary stasis due to the gravid uterus *These infections usually involve only the lower urinary tract because the incidence of pyelonephritis is not significantly increased

Postpartum Hemorrhage * In the British study, the risk of postpartum hemorrhage among : -singletons ……… 1.2% - twins …………….6% - triplets ………… 12% -quadruplets ……..21% *In a British population-based study of postpartum hemorrhage, multiple pregnancy was associated with more than fourfold increased risk

Postpartum Hemorrhage *predisposing factors: -Overdistention of the uterus uterine atony -risk for retention of placental tissue -surgical or mechanical trauma to the genital tract -pharmacologic effects of medications such as magnesium sulfate(which is frequently used to manage both preeclampsia and preterm labor