Bangladesh J Obstet Gynaecol, 2013; Vol. 28(2) : 92-99 Review Article Prenatal Management of Compromised SHAMSUN NAHAR BEGUM (HENA)1, NAZNEEN KABIR2, FAHIMA AKHTER3

Abstract: Compromised are those who are at increased risk in intrauterine life due to various factor resulting in increased mortality & morbidity. Fetal compromise in is difficult to assess. Diagnostic skills for fetal diseases have improved enormously, but therapeutic approaches remains limited. “The Fetus should be considered as a separate individual and fetal medicine now needs to move into phase of evidence based management. Due to relative rarity of fetal disorder, a multicentre study is needed and this is the challenge for the next decade of fetal medicine. Keywords: Compromised fetus, Antenatal surveillance, fetal medicine.

Introduction: fetal blood transfusion are the best examples of Fetal tachycardia,Reduced baseline variability, preventive, transplacental and invasive treatment Complicated variable decelerations, Late developed for more than a decade. Most significant decelerations, Prolonged decelerations may be advance in recognition of fetus as a separate individual 2 associated with fetal Compromse and require having their own right . further action. The features very likely to be associated It is also evident that fetal outcome is better in at risk with significant fetal compromise and require fetus than to low risk one because of increased materno- immediate management, which may include urgent fetal surveillance. Antepartum unexplained fetal death is birth are prolonged bradycardia( < 100bpm for > 5 by far the commonest cause of death after 20 wks of minutes), absent baseline variability, sinusoidal gestation comprising nearly 40% of deaths in this pattern,complicated variable decelerations with period3. So the main challenge in pregnancy care is to reduced baseline variability, late decelerations with improve fetal surveillance in low risk in order reduced variability. There is no research evidence to identify the potentially compromised fetus. The evaluating the benefits or risks associated with the emphasis in fetal care is now no longer exclusively on short term use of maternal facial oxygen therapy in survival but on the quality of that survival4. 1 cases of suspected fetal compromise . Fetal Compromisation in pregnancy are due to genetic, compromise in pregnancy is difficult to assess. Many chromosomal & congenital anomaly of fetus, maternal cases have no obvious cause and management has diseases, drugs, infection, endocrine, immunologic to be aimed at determining the optimum time of & idiopathic causes. In late pregnancy uteroplacental delivery. dysfunction (maternal disease, placental factor), fetal Antenatal Surveillance of at risk fetuses has become anomaly (chromosomal / structural), Congenital the standard of care for high risk obstetrical population. infection, Rh- isoimmunization, multiple gestation, postdated pregnancy and premature rupture of Fetal compromisation in intrauterine life is due to membrane( PROM) are the important factors. maternal, fetal, placental and idiopathic causes. Diagnostic skills with fetal disease have improved All these factor may results in , premature enormously, but therapeutic approaches remain delivery, intrauterine growth restriction (IUGR), limited. Peri-conceptional folate, maternal steroids and intrauterine death (IUD) and birth asphyxia.

1. Professor & Head, Department of Obs. & Gynae, Sir Salimullah Medical College Mitford Hospital, Dhaka 2. Professor & Head, Department of Obs. & Gynae, IInstitute of Child & Mother Health, Dhaka 3. Medical Officer, Department of Obs. & Gynae, Sir Salimullah Medical College Mitford Hospital, Dhaka Prenatal Management of Compromised Fetus Shamsun Nahar Begum (Hena) et al.

Aim of early detection of at risk fetus is to reduce the • Inhibin A incidence of perinatal morbidity & mortality, as 25- • Maternal hexosaminidase test 75% risk condition are amenable to prenatal modification prior to irreversible damage4. Ideally • Fetal cells in maternal circulation assessment of fetal wellbeing should start before onset The triple screen includes maternal serum AFP of fetal compromise. Optimal time to initiate testing (MSAFP), serum â-hCG, and unconjugated depends on-risk factor & previous obstetric history. (uE3); the addition of inhibin A results in the quadruple Initiate testing at early gestation in pregnancy with screen. The panel findings, along with , multiple risk factor is recommended. Common high can suggest a number of fetal abnormalities, depending risk maternal condition demanding fetal surveillance on the results pattern. Maternal weight, race, and are hypertension, diabetes, iso-immunization, multiple pregnancies may affect the risk calculation. chronic renal disease, SLE, congestive heart disease, According to ACOG, quadruple screening detect 67% haemoglobinopathies & hyperthyroidism. of trisomy 18, 80% of trisomy 21, and 80%-85% of Methods of fetal surveillance- neural tube defects (NTD) and/or abdominal wall includes screening and diagnostic defects. The addition of the first trimester PAPP-A tests, which are performed at different stages of and nuchal translucency tests increases detection gestation and have different risk-benefit profiles. rates of trisomy 18 to 79% and trisomy 21 to 85%. However, these additions do not improve detection Screening tests should be safe and minimally invasive, rates for the other conditions5. performed in ,low-risk populations to detect conditions in which a timely intervention can alter outcomes. B. Prenatal diagnostic tests Diagnostic tests are required to confirm a positive Prenatal diagnosis of fetal disorders and structural screening result. malformations is becoming increasingly important for several reasons. Approximately 3% of all pregnancies Prenatal screening tests are for various fetal result in the delivery of a baby with a genetic disorder metabolic, chromosomal, and anatomic defects. Until or birth defect. Minor malformations are found in an recently, pregnant women older than 35 were counseled additional 7%-8% of neonates. to proceed directly to diagnostic tests rather than to undergo screening tests first because of elevated risk. Diagnostic tests are indicated when the risk of chromosomal anomaly are present or suspected (eg, The American College of Obstetricians and advanced maternal age, suggestive fetal Gynecologists (ACOG) in 2007 issued prenatal testing ultrasonographic findings). by recommendations that include offering screening tests trained professionals in a timely and sensitive fashion to all pregnant women, regardless of age. is an essential adjunct to prenatal diagnosis. A. Prenatal Screening Test First-trimester diagnostic test- B. First-trimester screening test –Beta human • Fetal ultrasonography- chorionic gonadotropin (â-hCG): Lower value may indicate ectopic pregnancy or threatened abortion Fetal ultrasonography in the first trimester is the most reliablemethod of dating a pregnancy, reliably • Pregnancy-associated plasma protein-A diagnose anatomic abnormalities such as NTDs and (PAPP-A): measured in maternal blood at abdominal wall defects, congenital diaphragmatic 11-13 weeks of gestation. Combined with b- hernia, limb abnormalities, and cardiac defects, hCG (decreased PAPP-A levels and increased screening for nuchal lucency in conjunction with PAPP- b-hCG levels) and ultrasonography for nuchal A measurements to diagnose trisomy 216,7,8. translucency, more than 80% of trisomy 18 and 21 can be detected. • Chorionic villus sampling- Prenatal diagnosis prior to 12 weeks’ gestation for Second-trimester screening tests- detection of a chromosomal anomaly, DNA molecular • Maternal serum alpha-fetoprotein (MSAFP) diagnosis of classic genetic disorders, detection of • Serum â-hCG defects in lysosomal enzymes or mucopoly- • Unconjugated estriol (uE3) saccharidoses and. 21-hydroxylase deficiency causing 93 Bangladesh J Obstet Gynaecol Vol. 28, No. 2 congenital adrenal hyperplasia 9,10. Preimplantation • Advanced maternal age (>35 y) biopsy: in a fetus of parents with substantial risk of a • Previous offspring with chromosomal anomalies known genetic disorder and in women with repeated or birth defects miscarriages due to chromosomal translocation9,10,11,12. • Parental balanced translocation, inversion • Early (manifests as recurrent • Coelocentesis: pregnancy loss) Second-trimester diagnostic test- • Midtrimester amniocentesis • Suggestive fetal ultrasonographic findings • Percutaneous umbilical blood sampling or · Positive maternal screening test findings cordocentesis • Mother having a disease or exposed to drugs, • Late chorionic villus sampling medications, or infections • Fetal muscle and liver biopsy • Mendelian genetic trait in the parents Fetal well-being in the third trimester- • Molecular DNA diagnosis (cystic fibrosis, fragile • Amniocentesis X) • (NST) • test: NST with assessment of • Enzymatic activities in villi, amniocytes, or both volume (AFV), fetal breathing Treatments for fetal disorders- movements, fetal activity, and fetal muscle tone Fetal medicine is a complex undertaking that involves • a multidisciplinary team for prenatal diagnosis and • Doppler velocimetry: fetal umbilical arterial blood fetal therapy. Several issues, including ethical and flow velocity or resistance to flow legal considerations, are particular to fetal medicine; • Modified biophysical profile(MBBP) fetal treatment centers may provide solutions to many • Fetal kick count of these. A multidisciplinary team in fetal medicine Fetal kick count, non stress test & modified generally consists of the following members: biophysical profile are the screening test. • obstetrician BPP & CST is a back up test in case of abnormal • maternal-fetal medicine specialist MBPP. Doppler velocimetry is complementary to BPP. • geneticist or genetic counselor Antepartum monitoring of fetal heart rate is the most widely used method for fetal assessment in late • neonatologist pregnancy which is a poor predictor of fetal health • pediatric surgeon and is associated with a threefold increase in perinatal • obstetric sonologist death13. Assessment of high risk pregnancies by umbilical artery Doppler ultrasonography • Relevant pediatric subspecialists (eg, cardiologists, approximately half the perinatal death rate7. cardiothoracic surgeons, neurosurgeons, urologists) Radiologic studies- Magnetic resonance imaging (MRI): Important adjunct Ethically, the fetus as an individual is thought of in to ultrasonography5. different, the lack of legal clarity further confounds decision making. Important facts are : Computed tomography (CT) scanning: Limited applications in prenatal diagnosis • Maternal beneficence and autonomy versus fetal beneficence and autonomy Fetal magnetocardiography: Prenatal detection of a prolonged QT interval or Wolff-Parkinson-White • Vagaries of the legal status of the fetus as an syndrome Indications for Diagnostic Tests- individual. Conditions that increase the risk of chromosomal • Identifying viable and previable fetuses as anomaly include the following: candidates for treatment 94 Prenatal Management of Compromised Fetus Shamsun Nahar Begum (Hena) et al.

Fetal disorders that require treatment are- puncture or a combination of intraperitoneal and intravascular transfusions can be used. • Neural tube defects • Congenital adrenal hyperplasia Congenital adrenal hyperplasia Since the differentiation of external genitalia begins • Thyrotoxicosis at 7 weeks’ gestation, the mothers of all fetuses at • Hypothyroidism risk (those with a previously affected child) are given • Methylmalonic acidemia dexamethasone (0.25 mg PO qid) at 7-9 weeks. • Multiple carboxylase deficiency Thyrotoxicosis • Lung prematurity Fetal thyrotoxicosis is usually seen in infants of mothers with Grave disease or autoimmune thyroiditis. • Maternal human immunodeficiency virus (HIV) The diagnosis is made with cordocentesis. infection Maternal treatment with propylthiouracil (initial dose • Immune hydrops 300 mg/d PO, then titrate according to effect) or • Fetal thrombocytopenia methimazole is associated with a good fetal outcome.

• Fetal hemoglobinopathies, immune deficiency Hypothyroidism diseases, inborn errors of metabolism Fetal hypothyroidism is linked to maternal • Congenital heart disease hyperthyroidism, use of radioactive iodine, drugs, and excessive maternal iodine intake. • Certain fetal arrhythmias (eg, sustained supraventricular extrasystoles, atrial flutter), Fetal status is evaluated at ultrasonography and by supraventricular tachycardias, and congenital direct cordocentesis. complete heart block Intra-amniotic L-thyroxine initiated at 34 wk of gestation In-utero treatment- has been shown to cause regression of fetal goiters and normalization of hormone levels. Fetal anaemia and Immune hydrops- Causes of fetal anaemia are Rh isoimmunization, ABO Methylmalonic acidemia incompatibility, Fetal infection, haematological Prenatal cyanocobalamin has been empirically disorder. There is hepatosplenomegaly, dilated portal administered orally to the mother at a dose titrated to vein, polyhydramnios, placentomegaly, increase flow achieve high maternal plasma B12 levels and normal in portal vein & ductus venosus diagnosed by USG. maternal urinary methylmalonic acid excretion.

Screening for maternal antibody titer, fetal monitoring Multiple carboxylase deficiency by serial ultrasound and Doppler assessment of the This disorder is caused by a deficiency of velocity of blood flow in the middle cerebral artery holocarboxylase synthetase starting at 16-18 weeks’ gestation and repeated every Maternal biotin supplementation may prevent neonatal 1-2 weeks until 35 weeks’ gestation of at risk fetuses complications. is needed Serial amniocentesis (10 day to 2 week intervals) with Lung maturity induction measurement of bilirubin, beginning at 18 weeks, and Maternal corticosteroid therapy, used to induce lung determine when the result is abnormal from the maturity and surfactant synthesis in the fetus, has Queenan and Liley charts. been proven effective in significantly reducing respiratory distress syndrome (RDS) in the neonatal Serial cordocentesis is indicated for severely affected period. Controlled studies have shown a reduction from fetuses for direct measurement of hematocrit (Hct), 20.2% to 11.2%. Betamethasone (12 mg IM 24h for 2 reticulocyte count, and bilirubin. doses) or dexamethasone (6 mg IM q12h for 4 doses) Intrauterine transfusions can be performed as indicated is recommended for fetuses at less than 34 weeks’ based on the results of the diagnostic tests. Direct gestation. In 2009 a multicenter, randomized, placebo- intravascular transfusions through umbilical vein controlled trial had shown that the benefit of a single

95 Bangladesh J Obstet Gynaecol Vol. 28, No. 2 rescue course of steroids given prior to 33 weeks’ Fetal anomaly gestation outweighs the fetal/neonatal risks. Major structural anomaly occur in 2-3% of all Maternal HIV infection: pregnancies. It contributes about 20-30% of perinatal Maternal administration of zidovudine (AZT), started morbidity & mortality. Advance in ultrasound at 14 weeks’ gestation, continued throughout technology have contributed greatly in improvement pregnancy, and given intravenously during labor, of fetal outcome by diagnosing and evaluation of fetal followed by treatment of the neonate for the first 6 anomaly at appropriate time. weeks, has been documented to decrease the rate of Following are options for fetal therapy to manage vertical transmission from 25% to 8%. various fetal malformations:

Fetal thrombocytopenia- • Termination of the pregnancy Maternal thrombocytopenia has many causes, many • Elective cesarean delivery of which do not place the fetus at risk of bleeding. • Preterm delivery Fetal hematopoietic stem cell transplantation • Prenatal medical treatment Hematopoietic stem cell (HSC) transplantation in utero • Prenatal invasive is an attractive theoretical option for the treatment of congenital disease that can be diagnosed antenatally There is change in overall approach in managing and improved by engraftment of HSCs. pregnancy with fetal anomaly. The emphasis is no longer on termination but on rapid karyotyping and Diseases theoretically amenable to HSC tertiary referral to fetal medicine centers for intrauterine transplantation are hemoglobinopathies such as sickle fetal management. Golden period for cell disease and thalassemias, immune deficiency is 20-24 wks of gestation. Methodical supervision of diseases, and inborn errors of metabolism. all fetal organs by TIFFA (Targeted imaging for fetal Congenital heart disease anomaly) is indicated at risk condition. In high risk The precise diagnosis of congenital heart lesions with condition TVS at 13-14 wks for early anomaly scan is the aid of newer echocardiographic techniques has recommended by some authorities at present. created the potential for prenatal surgery or High risk situations for fetal anomaly screen are interventional catheterization. increased maternal age, diabetes, consanguinity, drug history, x-ray exposure, history of previous fetal Fetal arrhythmias anomaly. Other factors are clinical / laboratory findings Most fetal arrhythmias are benign, and 90% are atrial of small or large for date pregnancy & screen positive extrasystoles. . USG prompter for anomaly scan are Supraventricular tachycardias abnormal liquor, single umbilical artery & minor These must be treated if they are sustained and marker ( eg.echogenic bowel). Benefit of associated with hydrops or upon evidence of left atrial anomaly scan is to reassure the parent and counsel preexcitation and a small foramen ovale. for termination in lethal anomaly, need for additional test and therapeutic procedure in non-lethal anomaly. Digoxin is the first-line drug. Propranolol, Drawback of anomaly scan is that all anomaly not procainamide, and quinidine have also been used. recognizable sonologicaly and minor marker may Congenital complete heart block unstable the couple ( eg.,Choroid cyst) & operator This is associated with major congenital heart disease expertise directly interfere interpretation. in approximately 50% of cases. Intrauterine growth restriction (IUGR)- Diagnoses have included left atrial isomerism, IUGR refers to a condition in which the fetus is unable physiologically corrected transposition, atrioventricular to achieve its genetically determined potential size. canal defects, and ventricular septal defects. This The clinicians challenge is to identify IUGR fetuses group has a high incidence of congestive heart failure whose health is endangered in utero because of hostile or cyanosis and requires postnatal permanent intrauterine environment and to monitor & intervene pacemakers. appropriately. It also includes identifying small but 96 Prenatal Management of Compromised Fetus Shamsun Nahar Begum (Hena) et al. healthy fetus in order to avoid iatrogenic harm to them 13. An accurate early ultrasonic dating of pregnancy or their mother. Early onset IUGR associated with is important to avoid unnecessary induction for aneuploidy, structural anomaly, congenital infection. suspected poor growth(Type V evidence).. While late onset IUGR are associated with severe 14. Plasma volume expansion for impaired fetal uteroplacental dysfunction detected after 32 wks.of growth is theoretically promising (Type V gestation. Diagnosis of IUGR by history, clinical evidence). examination & appropriate investigations (serial USG, Doppler velocimetry).Treatment of IUGR includes rest, 15. Excessive alcohol consumption is associated avoid stress, smoking, alcohol, drug abuse and low with increased mortality and morbidity of dose aspirin. fetus(Type V evidence) Recommendations of 26th RCOG Study Group for fetal Once IUGR has been detected, the management surveillance are14,15: should depend on a surveillance plan that maximizes gestational age while minimizing the risk of neonatal 1. Smoking cessation programme is effective in morbidity & mortality. increasing mean birth weight (Type I evidence). Termination before 36 wks is indicated in evidence of 2. Nutrient therapy by dietary interventions and fetal hypoxia, anhydramnios, repeated late supplementation in suspected fetal growth deceleration, BPP score <6, fetal cardiovascular impairment is not effective. (Type I evidence). decompensation in Doppler study. 3. Fetal movement count in at risk cases may be better practice, but RCT provided no evidence of Multiple pregnancy- reduction in intrauterine death (Type I evidence) Twin to twin transfusion syndrome (TTTS) & Twin reverse arterial perfusion (TRAP) are the rare but 4. Routine screening by repeated BPP or Doppler serious complication of twin pregnancy. is not effective (Type I evidence). Treatment of Twin to twin transfusion syndrome by 5. Selective ultrasound is effective in identifying at serial amnioreduction & laser coagulation of the risk pregnancies(Type I evidence). communicating placental vessels is promising. 6. Measurement of fundal height has quite good But published studies of both procedures are non specificity and sensitivity in prediction of poor randomized uncontrolled and need multicentre growth (Type IV evidence). randomized controlled study for evaluation. 7. Doppler studies to monitor the high risk infant Selective embolization of of acardiac are effective to determine the optimum timing of twin in Twin reverse arterial perfusion (TRAP) can be delivery (Type I evidence). undertaken. 8. Biophysical profiles are not effective to monitor the high risk infant in improving outcome (Type I Oligohydramnios- evidence). Oligohydramnios causes fetal anomaly (Pul. hypoplasia, abnormal facies, limb positional defect). 9. Hospitalization and bed rest for suspected fetal Antepartum prevent pulmonary compromise are not effective (Type II evidence). hypoplasia and relieve cord compression. Intrapartum 10. Maternal oxygen therapy should only be used in amnioinfusion dilute thick meconium , reduce the risk selective cases(Type I evidence) of meconium aspiration syndrome and lower the rate 11. External is effective in of has been shown in meta- identifying deteriorating fetal condition in at risk analysis of published randomized trials. Simple preg. Its widespread use is not recommended maternal hydration may also increase amniotic fluid because of difficult interpretation(Type I volume. evidence). Polyhydramnios- 12. Routine use of calcium channel blockers is not Polyhydramnios causes preterm labour, maternal effective in pregnancy with impaired fetal growth oedema, oliguria, dyspnea. In acute symptom (Type II evidence). (maternal distress) induction of labour at or after 37

97 Bangladesh J Obstet Gynaecol Vol. 28, No. 2 wks & indomethacin, amnioreduction before 37wks. • Ultrasonography-guided vesicoamniotic, Associated congenital anomaly need termination of thoracoamniotic shunt pregnancy. • Fetoscopic techniques for ligation of umbilical Fetal surgery- cords in acardiac twins, selective Laser Fetal surgery (closed, open, or endoscopic) still be photocoagulation of communicating vessels in regarded in development phase. Closed surgical twin-to-twin transfusions, and ablation of procedure for lower urinary tract obstruction and posterior urethral valves hydrothorax has been done in many centres but no • Open fetal surgery randomized controlled trial is available. Open fetal Fetal surgery (closed, open, or endoscopic) still be surgery is associated with increased fetal mortality regarded in development phase. Closed surgical and maternal morbidity. procedure for lower urinary tract obstruction and Surgical interventions in invasive fetal therapy: hydrothorax has been done in many centres but no Anesthesia- As new intrauterine surgical techniques randomized controlled trial is available. Open fetal have been developed, anesthesia for the procedures surgery is associated with increased fetal mortality has also evolved. It is recommended that fetal analgesia and maternal morbidity. It is recommended that and sedation should be considered for invasive fetal analgesia and sedation should be considered procedures involving direct contact with the fetus after for invasive procedures involving direct contact with 12 23 wks of gestation. 7 The major objectives are to the fetus after 23 wks of gestation. ensure maternal and fetal safety. Specific goals are The surgical inventions are considered appropriate for the prevention of maternal hypoxia and hypotension, the following lesions: together with the maintenance of optimal uterine blood • Obstructive uropathy flow. Lower doses of epidural and spinal anesthetic • Hydrocephalus agents are needed in pregnant women because of • Pleural effusion increased epidural pressure and a lower volume of • Twin-to-twin transfusion syndrome cerebrospinal fluid in the vertebral space. • Amniotic band syndrome For surgeries involving direct fetal manipulation, • Congenital diaphragmatic hernia intramuscular fentanyl and pancuronium (a muscle • Congenital high airway obstruction syndrome relaxant and vagolytic) administered to the fetus have • Sacrococcygeal teratoma been tried prior to hysterotomy under ultrasonographic guidance. • Congenital cystic adenomatoid malformations

Monitoring During Surgery Conclusions: The parameters monitored during and after surgery Antenatal surveillance of at risk fetuses has become include the following: the standard of care for high risk obstetrical population. Fetal kick count , non stress test & modified • Myometrial contractions and intrauterine pressures biophysical profile are the screening test and BPP & • Maternal blood pressure, ECG, and pulse oximetric CST is a back up test. In case of abnormal MBPP, and blood gas levels Doppler velocimetry is complementary to BPP. Fetal medicine now needs to move into phase of evidence • Fetal pulse oximetric measurement ,heart rate, based management including randomized controlled blood gases and ECG trials. Due to relative rarity of fetal disorder a • Ultrasonographic findings in cases of fetoscopic multicentre study is needed and this is the challenge surgery for the next decade of fetal medicine. • Fetal temperature References: Surgical Interventions- 1. Fawole B, Hofmeyr GJ. Maternal oxygen Three approaches are currently used for invasive fetal administration for fetal distress. The Cochrane therapy- Database of Systematic reviews 2007(2).

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