Obstetric & Gynecology Hospital of Fudan Universtity Multiple pregnancy Kang Yu Obstetric & Gynecology Hospital of Fudan Universtity 2013-10-15

Multiple Pregnancy Incidence Twins：1:100 Triplets：1:10,000 Quadruplets：1:1,000,000 Quintuplets：1:100,000,000

Classification Dizygotic twins：2/3 influenced remarkably by race, heredity, maternal age, parity, and especially fertility treatment Monozygotic twins：1/3 independent of race, heredity, age, and parity

Dizygotic twins Two ovum, two sperm Different gene： appearance: different or alike gender：same or different Placenta： two placenta fuse to one placenta, twin peak, no communicated blood vessel

Monozygotic twin One ovum, one sperm same gene： appearance: same gender：same

Classification of monozygotic twin dichorionic diamniotic twins: 18～36% monochorionic diamniotic twins: 65% monochorionic monoamniotic twins: <1% 4 to 8 days Postfertilization 0 to 4 days 9 to 13 days >13 days Conjoined twins

Case One Shi ××, 26 years old Chief complaint：gravida 1 para 0, 27 weeks of gestation, found dyspnea one week and prostration three days. Present history：last menstrual period (LMP):12, June, 2011. estimated date of conception(EDC):19, March,2012. Urine chorionic gonadotrophin(HCG) was positive at thirty-seven days of gestation and the morning sickness was severe. One sac was found through altrasound in the first trimester. Regular prenatal examination was not perform. Twin pregnancy was found at 25 weeks of gestation. Dyspnea one week and prostration three days. Physical examination：T:36.8°C, P 98 counts per minute，R 18 counts per minute，BP 100/65mmHg

Ultrasound results： Fetus A: BPD(biparietal diameter)-HC(head circumference)-AC(abdominal circumference)-FL(femur length): 75-268-256-52mm, estimated weight 1454g, AFV(amniotic fluid volume):26cm, bladder was visible, no abnormal doppers. Fetus B: BPD-HC-AC-FL:65-236-206-44 mm, estimated weight 832g, AFV:1cm, bladder was visible, no abnormal doppers. AFI: 127-98-102-134, 461. no twin peak, amniotic separation was found.

Question 1:Diagnosis Gravida 1 Para 0, 27 weeks of gestation, twin pregnancy Monochorionic Diamniotic Twins(MC/DA) TTTS(stage 1)

Twin-Twin Transfusion Syndrome (TTTS) Blood is transfused from a donor twin to its recipient sibling The donor becomes anemic and its growth may be restricted The recipient becomes polycythemic and may develop circulatory overload manifest as hydrops Donor twin is pale, and its recipient sibling is plethoric

TTTS Anastomoses in monochorionic diamniotic placenta：arterio-arterial,venous –venous,arterio-venous Only arterio-venous anastomoses will result to TTTS.

Quintero staging system Stage I: polyhydramnios(>8cm) in recipient / aligodramnios(<2cm) in donor, but urine still visible sonographically within the donor twin's bladder Stage II: urine is not visible within the donor's bladder Stage III: abnormal Doppler studies of the umbilical artery, ductus venosus, or umbilical vein. Stage IV: ascites or frank hydrops in either twin Stage V: demise of either fetus I 羊水过多/羊水过少，供血胎膀胱可见， II 供血胎膀胱不可见， III 供血胎膀胱不可见，且任何一个胎儿出现异常多普勒血流（脐动脉舒张末期峰缺如或逆向，静脉导管逆流或脐静脉搏动） IV 出现胎儿水肿 V 胎儿死亡（一个或两个）

Question 2: Management An amnioreduction of 6.2 L was performed in the recipient sac. Tocolytics (magnesium sulfate）were administered. Follow up: ultrasound weekly Ten days later Ultrasound surveillance： anuria and virtually no amniotic fluid in the donor twin, polyuria and excess amniotic fluid in the recipient, and abnormal umbilical venous and ductus venosus flows in both twins.

Management Termination: Cesarean section premature donor and recipient twin boys were delivered, weighing 895 and 1450 g, with haemoglobin levels of 16.4 and 22.9 g/dl Both infants required mechanical ventilation and administration of surfactant due to respiratory distress syndrome. The donor twin developed acute renal failure and necrotising enterocolitis which required surgery. The recipient developed the polycythaemiae hyperviscosity syndrome which required a partial exchange transfusion. Both children are alive. Check the placenta after delivery: one placenta, two layer of membrane partition that separated twin fetuses , all associated with severe TTTS. In addition, in this case the neonatal criteria of TTTS were valid (a difference of >25% in birth weight, and >5 g/dl Hb).

Diagnosis TTTS (Prenatal) monochorionicity same-sex gender hydramnios defined if the largest vertical pocket is > 8 cm in one twin and oligohydramnios defined if the largest vertical pocket is < 2 cm in the other twin umbilical cord size discrepancy cardiac dysfunction in the recipient twin with hydramnios abnormal umbilical vessel or ductus venosus Doppler velocimetry significant growth discordance There have been dramatic changes in the criteria used to diagnose and classify varying severities of TTTS. Classically, weight discordancy and hemoglobin differences in monochorionic twins were calculated, however, it was soon appreciated that in many cases, these were later clinical findings.

Diagnosis (Postnatal) Examination in placenta, chorionic membrane, amniotic membrane Examination in neonate： Discordance in hemoglobin: ≥5g/dl Discordance in body weight : ≥15-20% 产后检查胎盘及羊膜囊间隔确定为单绒毛膜妊娠 双胎体重相差≥20％ 血色素相差＞5g/dL 双胎之小胎儿贫血 性别相同 单绒毛膜胎盘有血管吻合支 体重相差≥20％ 大胎儿羊水过多；小胎儿羊水过少，或固定胎（stuck twin） Bruner and Rosemond, 1993

Pregnancy Complications Kang Yu Obstetric & Gynecology Hospital of Fudan Universtity 2013-10-15

Pregnancy Complications Heart Diseases Hepatitis Diabetes Anemia … Appendicitis Cholecystitis Intestinal obstruction

Heart diseases in pregnancy

Clinical significance of heart disease in pregnancy Interaction between heart disease and pregnancy Mother: heart failure; infective endocarditis; hypoxia and cyanosis; thrombenbolism Baby: miscarriage, still birth, fetal growth restriction, fetal and newborn distress, preterm delivery Increased caesarean section rate

Heart diseases in pregnancy Can I have a baby? What is the risk for me and my baby? What should I do during the course of pregnancy? By which way should I delivery my baby? Any special thing to be paid attention to after birth?

Can I have a baby? NO YES Mild Cardiac function I～II Severe Cardiac function Ⅲ一Ⅳ History of heart failure Pulmonary hypertension Right-to-left shunts Severe arrythmia Active rheumatic heart disease Acute Myocarditis, endocarditis >35y with long history of cardiac disease YES Mild Cardiac function I～II No history of heart failure No complication

During Pregnancy Determine whether or not the pregnancy should be continued NO: induced abortion before 12 weeks YES: Intensive care during pregnancy Early diagnosis and treatment of congestive heart failure

During pregnancy Heart failure ---- prevention Limited physical activity Control of body weight: increase <12Kg (<0.5Kg / month) Limited salt intake: <4-5g/day Prevent risk factors: infection, anemia, arrhythmia, hypertensive diseases Dynamic observation of cardiac function

During Pregnancy Heart failure---early diagnosis Development of dyspnea and palpitation on exertion Heart rate >110 bpm; breath rate >20/min Nocturnal cough Persistent basilar rales

During pregnancy Treatment of heart failure Digoxin Diuretics Vessel dilating agents Termination of pregnancy: C-S Timing Termination after heart failure is controlled C-S when heart failure could not be controlled

Intrapartum management Pattern of delivery Cesarean section Vaginal delivery Heart function I-II Very good obstetrical condition Vaginal delivery---- prevent heart failure First stage: intensive care and sedation Second stage: shorten the course Third stage: Add pressure on abdomen prevent postpartum hemorrhage

Puerperium management Intensive care during the first 3 days Prevent infection Breast feeding Sterilization

Viral Hepatitis in Pregnancy

Viral Hepatitis in Pregnancy Interaction between pregnancy and hepatitis Diagnose, Differential diagnosis and treatment Pathway of maternal – fetal infection and prevention

Impact of pregnancy on viral hepatitis Heavier liver burden Compromised defending ability of liver More complicated and severe condition in pregnant patients

Impact of hepatitis on pregnancy Early Pregnancy Serious pregnancy reaction Abortion Malformation Late pregnancy Hypertension Postpartum hemorrhage Preterm delivery, fetal death, stillbirth

Impact of hepatitis on pregnancy Maternal - fetal infection HBV Intrauterine Intrapartum—main route of transmission Fetal swallowing in genital tract Mother blood leaking into fetal circulation Postpartum: breastfeeding, salivary

Differential diagnosis Intrahepatic cholestasis of pregnancy （ICP） Happen during late pregnancy Pruritus Jaundice Cholic acid fetal death

Differential diagnosis Acute fatty liver of pregnancy Late pregnancy, acute and severe hepatic disfunction, fat filled hepatic cell HELLP syndrome Hypertension, hemolysis, BPC, elevated liver enzyme Hyperemesis gravidarum Light liver dysfunction, negative virus marker Drug induced hepatitis History of drug intake

Management Rest Nutrition Protection of liver function Prevent infection and further damage Fluminant hepatitis

Management Delivery C-S is preferred Vitamin K1 20-40mg im several days before delivery Prevent postpartum hemorrhage Fulminant hepatitis: C-S 24 hours after active treatment

Management Pureperium Prevent from damaging liver function Breast feeding: Stop if HBsAg, HBeAg, anti-HBc, HBV-DNA positive

Diabetes complicating pregnancy

Diabetes complicating pregnancy Gestational diabetes mellitus (GDM) and overt diabetes complicating pregnancy Diabetes  pregnancy Screening and diagnosis Management of women complicating diabetes during pregnancy

Gestational diabetes mellitus GDM >90% Incidence: 2.9% (1.5-14.0%) Type 1 is characterized by lack of insulin (a production problem) Type 2 is characterized by plentiful insulin that is not able to do its job effectively (a function problem – i.e., lack of response, hence the term “insulin resistance”) Gestational diabetes mellitus GDM >90%

Impact of pregnancy on diabetes Insulin resistance and insufficiency Increased glucose demands---hypoglycemia Insulin overdose after delivery

Maternal and fetal effects Maternal effects Hypertensive disorders （高血压） Infection （感染） Ketoacidosis （酮症酸中毒） Spontaneous abortion （自发流产） Polyhydramnios （羊水过多） Dystocia （难产） and C-S owing to macrosomia （巨大儿） Recurrent GDM （再次妊娠时复发）

Maternal and fetal effects Macrosomia （巨大儿） Fetal growth restriction （胎儿宫内生长受限） Spontaneous abortion & Preterm delivery （自发流产和早产） Malformation （胎儿畸形）

Maternal and fetal effects Neonatal effects Respiratory distress （呼吸窘迫） Hyperinsulinemia Pulmonary Surfactant  Delayed pulmonary maturation Hypoglycemia （低血糖）

Diagnosis----GDM History: family, previous pregnancy, present pregnancy Screening: 50-g oral glucose challenge test （24-28 weeks） Confirmed diagnosis OGTT: 75/100-g oral glucose tolerance test

The 50 gr. GCT (Cutoff >140 mg/dl, 7.8mmol/L) Sensitivity: 93.3% Specificity: 38.2% Positive Predictive Value: 78.6 % Negative Predictive Value : 70.0 %

Method Criteria (mmol/L) Diagnostic criteria for GDM---OGTT Method Criteria (mmol/L) FPG 1 hr. 2 hr. 3 hr. WHO (75 g) 5.6 10.3 8.6 6.7 Diagnosed when 2 or more values are abnormal FPG: Fasting plasma glucose

Diagnosis—Overt diabetes polydipsia （多饮）, polyuria （多尿）, unexplained weight loss，ketoacidosis Random plasma glucose >200 mg/dL(11.1 mmol/L); fasting glucose>126mg/dL (7 mmol/L)

Management Purpose Maintain glucose level within normal range Minimize fetal and maternal complication Lower peripartum fetal and neonatal mortality

During pregnancy Diet To provide the necessary nutrients for the mother and fetus To control glucose levels To prevent starvation 30-35kcal/kg of ideal body weight 55% carbohydrate 20% protein 25% fat 3 meals and 3 snacks daily Intensified monitoring Fasting glucose <3.3-5.6mmol/L Postprandial glucose <6.7mmol/L

During pregnancy Drug treatment: Insulin only Individualized

Assessment of mother Glucose / ketone monitoring （监测血糖/酮体） Retinal photograph (眼底) Renal function （肾功能） Glycated Haemoglobin （糖化血红蛋白）

Assessment of fetal well-being Daily fetal movement counting NST AFV or biophysical profiles

Delivery WHEN? after 38 completed weeks Before 38 weeks when Fetal lung muturation Before 38 weeks when Unsatisfied glucose control Maternal complication: infection, severe preeclampsia; vascular diesease Fetal distress or FGR Caution in the use of corticosteroids

Delivery HOW? Diabetes itself is not the indication for C-S C-S when indicated: macrosomia, compromised placenta function, etc. Stop subcutaneous insulin 3 hours before operation

Delivery Vaginal delivery Close monitoring Glucose monitoring: >5.6mmol/L (100mg/dL) Control the whole course within 12 hours

Postpartum Insulin dose decrease 1/2 -1/3 after delivery Encourage follow up with health care provider to have OGTT (6 weeks to 6 months 75 g OGTT) weight management, postpartum visit with a registered dietitian Encourage breastfeeding Monitoring occasionally with meter Future pregnancy

Neonatal management Treated as preterm baby 25% glucose intake 30 minutes after delivery Prevent complications

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