By I. Korda.. Many drugs may used in the pregnancy are found to be harmful in nature.. Drug Transfer to the Fetus may be by Passive diffusion Facilitated.

By I. Korda.

Many drugs may used in the pregnancy are found to be harmful in nature..

Drug Transfer to the Fetus may be byPassive diffusionFacilitated diffusionActive transportPlacental surface areaPlacental metabolism

Drugs can be harmful for the unborn fetusAcross PlacentaMolecular weightLipid solubilityIonization Protein binding

Congenital Malformations3-4% of all babies are born with a major

birth defect

Of these, 50% are of unknown cause

Consider teratogen exposure andrealize genetics plays a role

TERATOGENSA substance, organism, physical agents or

deficiency state capable of inducing abnormal structure or function such as:

Gross structural abnormalitiesFunctional deficienciesIntrauterine growth restrictionBehavioral aberrations

Teratogenic FactorsTime of exposureDevelopmental stage during

exposureMaternal dose and durationMaternal pharmacokineticsGenetic factors/phenotypesInteractions between agents

Teratogenic agents

1) Drugs and chemicals

2) Infectious agents

3) Radiation

4) Other

periods of pregnancy, when the fetus is most susceptible to the damaging effects of

drugs:

1. Up to 11 days from the moment of conception.  2. On the 11th day prior to the third week, when the fetus

begins the period of organogenesis.  3. Between 4 and 9 weeks of when the danger of fetal growth

retardation, but teratogenic practically does not occur.  4. The fetal period (9th week before birth). In this period, the

growth of structural defects usually do not occur, but may be in breach of postnatal functions and various behavioral abnormalities.

Multifetal gestation :

CAUSES :Increasing maternal

ageIncreasing parityNutritional factorsPituitary

gonadotropinInfertility therapyAssisted

reproductive therapy

Fraternal Twin

Fertilization of two separate ova

“double – ovum”, or dizygotic

monozygotic (MZ) twins

Identical TwinsTwins arise from

single fertilized ovum

“single-ovum”, monozygotic

Have increased incidence of discordant malformations

Determination of ZygosityUltrasoundCan determine zygosity as early as the first trimesterDizygotic: presence of two separate placentas and a thick –

generally 2mm or greater – dividing membrane (“twin – peak” sign)

Monozygotic: membrane generally less than 2mm in thickness and reveals only 2 layers. ( “T” sign) 

Placental ExaminationVisual examination of the placenta and membranesPlacenta should be carefully delivered to preserve the attachment

of the amnion and chorion to the placenta

Infant Sex and ZygosityTwins of the opposite sex are almost always dizygotic

Diagnosis of Multiple FetusesIn women with a uterus that appears large for

gestational age, the following possibilities are considered:

Multiple fetuses Elevation of the uterus by a distended bladder Inaccurate menstrual history Hydramnios Hydatidiform mole Uterine myomas A closely attached adnexal mass Fetal macrosomia (late in pregnancy)

Diagnosis of Multiple FetusesUltrasonography Separate gestational

sacs can be identified early in twin pregnancy

Two fetal heads or two abdomens should be seen in the same plane, to avoid scanning the same fetus twice and interpreting it as twins.

Diagnosis of Multiple FetusesRadiologic ExaminationNot useful and may lead to an

incorrect diagnosis

Biochemical TestAmounts of chorionic

gonadotropin in plasma and in urine, on average, are higher than those found with a singleton pregnancy, but not so high as to allow a definite diagnosis of multiple fetuses

Superfetation An interval as long as or longer than a

menstrual cycles intervenes between fertilizations.

Requires ovulation and fertilization during the course of an established pregnancy

Not yet proven in humans Superfecundation

Fertilization of two ova within the same menstrual cycle but not as the same coitus, nor necessarily by sperm from the same male.

Maternal AdaptationNausea and vomiting in

excess of that characterizing singleton pregnancies.

Maternal blood volume expansion is greater

Increased in cardiac out of 20%

Blood loss for twin delivery via NSD

935 ml

Pregnancy OutcomeAbortionMalformation

- Defects resulting from twinning itself. This category includes conjoined twinning, acardiac anomaly, sirenomelia, neural-tube defects, and holoprosencephaly.- Defects resulting from vascular interchange between monochorionic twins. Vascular connections may also conduct dramatic blood pressure fluctuations, causing defects

such as microcephaly, hydranencephaly,

intestinal atresia, aplasia cutis, or limb amputation.- Defects that occur as the result

of crowding.Low birth weightPreterm birth

Conjoined TwinsPosterior (pygopagus)

Anterior (thoracopagus)

Conjoined TwinsCephalic (craniopagus) Caudal (ischiopagus)

Twin reversed-arterial-perfusion (TRAP) sequence

It is a rare (1 in 35,000 births) but serious complication of monochorionic, monozygotic multiple gestation.

In the TRAP sequence, there is usually a normally formed donor twin who has features of heart failure as well as a recipient twin who lacks a heart (acardius) and various other structures.

Caused in the embryo by a large artery-to-artery placental shunt, often also accompanied by a vein-to-vein shunt.

The perfusion pressure of the donor twin overpowers that in the recipient twin, who thus receives reverse blood flow from its twin sibling.

Acardiac Twinacardius acephalus -

Failure or disrupted growth of the head

acardius myelacephalus - partially developed head with identifiable limbs

acardius amorphous - failure of any recognizable structure to form

Twin to Twin TransfusionBlood is transfused from a donor

twin to its recipient sibling such that the donor becomes anemic and its growth may be restricted, whereas the

Recipient becomes polycythemic and may develop circulatory overload manifest as hydrops.

Donor twin - pale, recipient sibling – plethoric

Fetal consequences:circulatory overload with heart

failure Occlusive thrombosis is also much

more likely to develop in this setting.

Polycythemia may lead to severe hyperbilirubinemia and kernicterus

Pathophysiology:

Presence of solitary, deep arteriovenous channels within the capillary beds of the villous tissue.

Velamentous umbilical cord insertion may contribute to the development of unequal fetal blood volumes because the membranously inserted cord can be easily compressed, restricting blood flow to one twin.

Diagnosis:postnatal diagnosis:

- weight discordancy between twins of 15 – 20%- hemoglobin level difference of 5 g/dL or greater

Typically presents in the midtrimester when the donor fetus becomes oliguric due to decreased renal perfusion.

Develops oligohydramnios, and the recipient fetus develops severe hydramnios, presumably due to increased urine production.

Virtual absence of amnionic fluid in the donor sac prevents fetal motion, giving rise to the descriptive term stuck twin.

Hydramnios–oligohydramnios combination can lead to growth restriction, contractures, and pulmonary hypoplasia in one twin, and premature rupture of the membranes and heart failure in the other.

Management

Without treatment, the donor or "pump" twin has been reported to die in 50 to 75 percent

Methods of in utero treatment of acardiac twinning: goal is interruption of the vascular communication between the donor and recipient twins.

Managementamnioreduction septostomylaser ablation of vascular anastomoses

selective feticide

Discordant Twins

Size inequality of twin fetuses, which may be a sign of pathological growth restriction in one fetus, is calculated using the larger twin as the index.

As the weight difference within a twin pair increases, perinatal mortality increases proportionately.

Restricted growth of one twin fetus usually develops late in the second and early third trimester and is often asymmetrical.

Earlier discordancy is usually symmetrical and indicates higher risk for fetal demise.

The earlier in pregnancy discordancy develops, the more serious the sequelae.

PathologyIn monochorionic twins, discordancy is usually

attributed to placental vascular anastomoses that cause hemodynamic imbalance between the twins.

Dizygotic fetuses may have different genetic growth potential, especially if they are of opposite genders.

DiagnosisWeight of larger twin minus weight of

smaller twin, divided by weight of larger twin.

Most useful index of size discordancy - ultrasonographic assessment of twin discordancy: abdominal

circumference superior to head circumference, femur length, or transverse cerebellar diameter

ManagementUltrasonographic monitoring of growth within a twin

pair has become a mainstay in the management. Other ultrasonographic findings, such as

oligohydramnios, may be helpful in gauging fetal risk. Depending on the degree of discordancy and the

gestattional age, fetal surveillance may be indicated, especially if one or both fetuses exhibit growth restriction.

Delivery is usually not performed for size discordancy alone, except occasionally at advanced gestational ages.

Death of One FetusPrognosis for the surviving twin depends on the gestational

age at the time of the demise, the chorionicity, and the length of time between the demise and delivery of the surviving twin.

Early demise such as a "vanishing twin" does not appear to increase the risk of death in the surviving fetus after the first trimester.

Later in gestation, the death of one of multiple fetuses could theoretically trigger coagulation defects in the mother.

Management decisions should be based on the cause of death and the risk to the surviving fetus.

Majority of cases of a single fetal death in twin pregnancy involve monochorionic placentation.

Antepartum Management of Twin Pregnancy

Delivery of markedly preterm infants be prevented.

Failure of one or both fetuses to thrive be identified and fetuses so afflicted be delivered before they become moribund.

Fetal trauma during labor and delivery be avoided.

Expert neonatal care be available.

Antepartum Surveillance

Assessment of amnionic fluid volume - associated oligohydramnios may indicate uteroplacental pathology and should prompt further evaluation of fetal well-being.

The nonstress test or biophysical profile is commonly used in management of twin or higher-order multiple gestation.

Doppler evaluation of vascular resistance - Increased resistance with diminished diastolic flow velocity often accompanies restricted fetal growth.

Delivery of Twin FetusesComplications of labor and

deliverypreterm labor, uterine contractile

dysfunctionabnormal presentation,

prolapse of the umbilical cordpremature separation of the

placentaimmediate postpartum

hemorrhage

Recommendations for intrapartum management

include:An appropriately trained obstetrical attendant should remain with

the mother throughout labor. Continuous external electronic monitoring or, if the membranes are ruptured and the cervix dilated, simultaneous evaluation of both the presenting fetus by internal electronic monitoring and the remaining sibling(s) by external monitors, is typically used.

Blood transfusion products should be readily available.An intravenous infusion system capable of delivering fluid rapidly

should be established. In the absence of hemorrhage or metabolic disturbance during labor, lactated Ringer or an aqueous dextrose solution is infused at a rate of 60 to 120 mL/hr.

An obstetrician skilled in intrauterine identification of fetal parts and in intrauterine manipulation of a fetus should be present.

Vaginal Delivery of the Second Twin

As soon as the presenting twin has been delivered, the presenting part of the second twin, its size, and its relationship to the birth canal should be quickly and carefully ascertained by combined abdominal, vaginal, and at times intrauterine examination.

If the fetal head or the breech is fixed in the birth: moderate fundal pressure is applied and

membranes are ruptured. digital examination of the cervix is repeated to

exclude prolapse of the cord. Labor is allowed to resume, and the fetal heart

rate is monitored. With reestablishment of labor there is no need

to hasten delivery unless a nonreassuring fetal heart rate or bleeding develops.

If contractions do not resume within approximately 10 minutes, dilute oxytocin may be used to stimulate contractions.

Vaginal DeliveryWhen the first twin is cephalic,

delivery can usually be accomplished spontaneously or with forceps.

As in singletons, when the first fetus presents as a breech, major problems are most likely to develop if:- fetus is unusually large and the after coming head is larger than the capacity of the birth canal.- Fetus is sufficiently small so that the extremities and trunk are delivered through a cervix inadequately effaced and dilated to allow the head to escape easily.- umbilical cord prolapses.

Vaginal Delivery of the Second Twin

If the occiput or the breech presents immediately over the pelvic inlet but is not fixed in the birth canal

Presenting part can often be guided into the pelvis by one hand in the vagina while a second hand on the uterine fundus exerts moderate pressure caudally.

Alternatively, an assistant can maneuver the presenting part into the pelvis using ultrasonography for guidance and to monitor heart rate.

It is essential to have an obstetrician skilled in intrauterine fetal manipulation and an anesthesiologist skilled in providing anesthesia to effectively relax the uterus for vaginal delivery of a noncephalic second twin to obtain a favorable outcome.

Cesarean DeliveryIn general, cesarean delivery is the method of choice when the first twin is noncephalic.It is important to place patients in a left lateral tilt

so as to deflect the uterine weight off the aorta to avoid hypotension.

The uterine incision should be large enough to allow atraumatic delivery of both fetuses.

It is important that the uterus remain well contracted during completion of the cesarean delivery and thereafter.

Remarkable blood loss may be concealed within the uterus and vagina and beneath the drapes during the time taken to close the incisions.

Thanks for attention!!!