For HealthCare

Rubella in pregnancy

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 *Q1* *How to avoid Rubella Infection* ?

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It’s a good practice point to *screen every woman with Rubella IgG* who wishes to become pregnant (UK does it, France and Austria also screen for Toxoplasmosis.

Obviously a *positive Rubella IgG indicates past infection and hence immunity* and these women can safely Plan for pregnancy. 

However *Rubella IgG negative women should be offered Rubella Vaccine* (R-Vac, 0.5ml, Serum Institute, Rs 70/-) following which a *minimum of One month (Maximum three months) should be waited for before pregnancy.* 

 *If a woman is seen directly in pregnancy, Even then screening for Rubella IgG is recommended* along with HBSAg, HCV, VDRL and HIV and IgG positive woman should be reassured.

However Rubella IgG negative women *in pregnancy can’t be offered Rubella vaccine (Live attenuated virus)* and therefore should be advised to *refrain from coming in contact with* any Known Rubella Infected person, Kids, Person with Cough and cold etc.

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 *Q2* *What is to be done in Women with a suspicious History of contact with Rubella* ? 

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 *Understanding the SEROLOGY is the key note* 

Rubella infection is diagnosed by serology. For pregnant woman who is Rubella IgG negative and comes to you with a suspicion of coming in contact with Infected Rubella or has a clear signs and symptoms of Rubella ( lymphadenopathy , erythematous rash and low-grade fever) , *three serology tests are helpful: IgG, IgM and Avidity:* 

 *Remember IgM indicates acute infection or a rare re-infection* . It starts to build up in serum in 5-7 days and vanishes after 6 months. IgM serology done within 5 days can come negative and hence should be repeated to confirm.

 *IgG also starts to build up after 7 days and generally is life long after that* 

IgG avidity is done to see its strength of attachment to antigen : *In recent (less than 3 months) this attachment is weak and the Avidity comes low* 

 *In older infections (more than 6 months) IgG attachment comes strong, Avidity is high* 

Three categories of serology is expected:

 *Scene 1 : IgM +ve and IgG -ve* 

This indicates recent infection however a repeat serology for confirmation within 14-21 days (minimum 7days ) is highly recommended  : if positive needs termination if GA < 12 weeks

 *Scene 2: IgM +vE and IgG +vE* 

This can be Acute infection (Remember after 7 days both IgM and IgG can appear), or Re infection or Old infection of just 6 months (where IgM are disappearing).To differentiate between these scenarios, we need to do IgG Avidity.

 If Avidity is strong that means this IgG is indicating Old infection and hence positive IgM in this case is either Re-infection (which very rarely is problematic to fetus) or a 6 months old infection with IgM disappearing but not completely gone out of the blood ( again no problems to the fetus.

If avidity is weak, It indicates a recent infection within three months and hence can cause problems to the fetus .Counsel for termination if GA < 12 weeks. if gestation > 12 weeks Amniocentesis for Rubella RNA PCR from amniotic fluid  is recommended.Alternatively  cordocentesis (Fetal Blood sampling) for IgM can also be done.

 *Scene 3 : IgM -ve and IgG +ve* 

This generally indicate an Old infection ( indicating immunity) but  doing IgG avidity is still strongly recommended.

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 *Q3* : *Chances of Fetal* *affection and how to diagnose it and what’s the management plan* ?

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Remember a maternal infection does not mean Fetal infection and a fetal infection doen not necessarily mean Congenital Defect or syndrome. *If the maternal infection has happened before 12 weeks of gestation, the risk of fetal infection is 90% with the risk of developing any rubella associated congenital defects as high as 90%.* The risk of fetal infection is about 55% at 12–16 weeks and congenital defects at 20% .However after after 16 weeks although the risk of fetal infection is still 45% but Risk of congenital defect low with only concern being sensori-neural deafness.

Based on above statement, *if a proven maternal Rubella infection occurs before 12 weeks (where there are 90% chance of fetal affection and 90 % chance of congenital abnormality) Termination is the best answer.* 

 *For an infection occurring after 12 weeks, best way to assess fetal affection is by Amniocentesis to check reverse transcriptase PCR (RT-PCR)* for the detection of viral nucleic acid in amniotic fluid. In cases where RT-PCR comes positive indicating fetal affection (controversial though) a Termination can be advised. For patients who are keen on pregnancy and not willing for termination can be monitored by serial monthly ultrasounds and a foetal echocardiography at 22 weeks. 

Remember some guidelines *recommend screening for Parvovirus IgG and IgM* in every suspected case of Rubella as clinical presentation of both is similar and disguise.

*Chickenpox in pregnancy* 

 *Courtesy:* _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ 

We have two case scenarios which would help us to understand this dilemma:

 *Case 1:*  A 28 year old primigravida with 8 weeks pregnancy comes to your clinic with frank chicken pox?

 *Case 2:* A 32 year old primigravida with 36 weeks pregnancy comes to your clinic with frank chicken pox?

 *In the First case where Primi with 8 weeks pregnancy developed frank chicken pox (rashes),First thing that comes to clinician and patient’s mind is termination,  Remember, No Guidelines recommend Direct termination of pregnancy, However surveillance is recommended* 

The probable reason for this is due to the fact that the risk of fetal affection (Congenital Varicella syndrome) is *just 0.4% prior to 13 weeks of gestation and 2% between 13–20 weeks and Almost 0% between 20–36 weeks of gestation.* 

Now for the symptomatic relief to the pregnant mother with frank chicken pox at 8 weeks, Acyclovir 800 mg, five times a day, for seven days can be given. *Remember RCOG doesn’t recommend using Acyclovir before 20 weeks and 24 hours after development of rash, other international guidelines (Canadian and Swiss) support its use at any time.*

 And yes to reassure you all, we have enough Data to suggest that there is *no increase in the risk of major foetal malformation with acyclovir exposure in pregnancy.*

Also there is a *limited role of intravenous immunoglobulins (VZVIg)* in the treatment of chickenpox once the rashes have already developed.

Coming to a concern about foetal surveillance in this case, Although PCR of amniotic fluid (Through Amniocentesis) for VZV DNA is the method of choice for the determination of whether or not the foetus has been infected, *Prenatal diagnosis relies on the identification of a combination of signs on a detailed ultrasound examination, such as limb deformities, microcephaly, hydrocephaly, polyhydramnios, soft tissue calcification and intrauterine growth restriction.*As the clinical features are a result of reactivation of VZV, *time is needed for this damage to manifest itself* . Accordingly, *no less than 5 weeks from the time of maternal rash should be permitted before the first detailed scan is performed,* as scans at less than 4 weeks intervals have resulted in missed diagnoses. A suscpiuos ultrasound finding of CVS confirmed by Amniocentesis PCR warrants detailed discussion with the couple and is highly recommended for termination of pregnancy.

 *In the second case where Frank Chicken pox develops at 36 weeks, the major concern now is to protect the “would be delivering” baby from developing clinical chicken pox (Neonatal Varicella) as congenital problems(congenital Varicella Syndrome) are not seen at this gestation* 

Ideally A planned delivery should be *avoided for at least 7* days after the onset of the maternal rash to allow for the passive transfer of antibodies from mother to child. In cases where delivery has to be conducted in this time frame ( e.g. foetal Distress, patient going in labour or a bleeding Previa etc), One should be aware of the fact that *Delivery in viremia may precipitate maternal haemorrhage and/or coagulopathy due to thrombocytopenia or hepatitis.*

 If a Caesarean section is planned (Elective or Emergency) *General anaesthesia is avoided* and more preferred choices are *Spinal* (avoided if active lesion on the site of spinal) and *Epidural* (Preferred as Dura is not punctured and hence transmission of virus from skin to CNS is less).

 *A neonatologist must be informed and prophylaxis with VZIG with or without acyclovir should be administered to the neonate as soon as possible* there is no need to test in these circumstances. The neonate should be monitored for any complications as the immunity is expected to be low. *Breast feeding is allowed* unless active lesions are close to nipple for a hindrance .In that case expressed milk can be taken.

 *PROMISE* *ULTRASOUND AND FETAL MEDICINE CENTRE* 

 *302, DEFENCE COLONY NEAR BUS STAND JALANDHAR*

 *Placenta Accreta Important Message* 

 *How many times, while operating a previous caesarean section patient, we have thought beyond adhesions and ruled out placenta accreta / Increta or Percreta* 

 *So far PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE was able to correctly diagnose placenta accreta / Increta in 11 cases. These were duly informed to the concerned Obstetrician and thus the surgery was planned with all the necessary consents and preparations. All these 11 cases ultimately landed up in Obstetrical hysterectomy.* 

Let’s discuss placenta accreta in brief:

 *Placenta accreta* is described when a part or entire placenta invades and becomes  inseparable from the uterine wall (decidua). In *placenta Increta* the chorionic villi invade the myometrium whereas in *placenta* *percreta*  invasion progresses through the myometrium and serosa, and occasionally into adjacent organs, such as the bladder.

Placenta accreta becomes problematic during delivery when the placenta does not completely separate from the uterus and is followed by *massive obstetric hemorrhage, leading to disseminated intravascular coagulopathy; the need for hysterectomy; surgical injury to the ureters, bladder, bowel, or neurovascular structures; adult respiratory distress syndrome; acute transfusion reaction; electrolyte imbalance; and renal failure.* 

 *The average blood loss at delivery in women with placenta accreta is 3,000–5,000 mL* .

 *As many as 90% of patients with placenta accreta require blood transfusion, and 40% require more than 10 units of packed red blood cells* . 

Maternal mortality with placenta accreta has been reported to be as high as *7%.* 

The Most Important risk factor for Placenta accreta is *previous cesarean delivery* with other being advanced maternal age and multiparity, or *any condition resulting in myometrial tissue damage followed by a secondary collagen repair, such as previous myomectomy, endometrial defects due to vigorous curettage resulting in Asherman syndrome, submucous leiomyomas, thermal ablation, and uterine artery embolization* 

The ultrasonographic features suggestive of placenta accreta include *irregularly shaped placental lacunae (vascular spaces) within the placenta ( Most predictive sign)* , thinning of the myometrium overlying the placenta, loss of the retroplacental “clear space,” protrusion of the placenta into the bladder, increased vascularity of the uterine serosa–bladder interface, and turbulent blood flow through the lacunae on Doppler Ultrasonography.

 Although most studies have suggested comparable diagnostic accuracy of MRI and ultrasonography for placenta accreta, MRI is considered an adjunctive modality and adds little to the diagnostic accuracy of ultrasonography. However, when there are ambiguous ultrasound findings or a suspicion of a posterior placenta accreta, with or without placenta previa, ultrasonography may be insufficient

 *So In conclusion,* Suspicion and early diagnosis of Accreta helps in counselling and planning the management so that it saves the obstetrician from catastrophic obstetrical emergency and unnecessary legal hassles.

 Rh Iso-immunization*

 *(Follow up of ICT +ve patient* ) 

Mrs Rekha (Name changed), 33 years, B-ve blood group with Husband  being O+ve, second gravida with previous one live issue and had received *Anti-D antenatally and postnataly in previous pregnancy,* Now referred to _PROMISE ULTRASOUND AND FETAL MEDICINE CENTER_ at *15 weeks with ICT positive* ( only qualitative done  at previous center).

Lets discuss the management

 *Step One* :  

 *Ask for quantitative ICT (i.e. Titre values)* 

Patients titre was 1:8.

Remember A critical titre is defined as antibody levels which pose a significant risk of fetal anemia or Hydrops. For RHD antigen critical titre is 1:16 or 1:32 depending on the laboratory threshold. Significant risk of fetal anaemia or hydrops is present once critical titres are reached or there is sudden rise in antibody level. A previous Injection of Anti-D may present as ICT positive in present pregnancy especially if interpregnancy interval is less than three years however the titres would be low (1:4 or Even not detected)

 *Step Two:* 

 *Monitor quantitative ICT (i.e. Titre values) every month till 28 weeks and every 15 days till delivery to see if titres remain below critical titres.* In any event of potential feto-maternal hemorrhage (Like Bleeding in previa or abruption or abdomen blow) it should be repeated after every episode. *Unfortunately, after two months, at 26 weeks, our patient, without any above said event, developed titres 1:32 (checked twice by laboratory).* 

 *Step three* : 

Since this patient has reached critical titres, *a weekly Ultrasound monitoring for for potential development of fetal anemia is recommended.* It is monitored though *Peak systolic velocity (PSV) of Middle cereblar artery ( MCA)* which is to be kept *below 1.5 MOMs* for gestation  and  other *signs of Fetal anemia* _(like pericardial effusion, Tricuspid regurgitation, Placentomegaly, Polyhydraminos, scalp edema, skin edema, Ascites and finally fetal hydrops)_ are also to be looked upon. In other patients, where the critical titres are not reached, as discussed monthly titre monitoring with routine Ultrasonography is advised.

Our patient was monitored by MCA PSV and other USG signs of fetal anemia, delivered at 37 weeks with a healthy 2.8 kg female baby who required 7 days of NICU Admission for Mild neonatal jaundice with no requirement for exchange transfusion.

 *In Continuation:*

 Had the MCA PSV increased to more than 1.5 MOM for gestation, indicating severe fetal anaemia, An Intrauterine Blood Transfusion would have been needed. Where ultrasound guided percutaneous umbilical blood sampling is performed to know the fetal haemoglobin and hematocrit followed by blood transfusion.

We proudly announce that services of Intrauterine Blood Transfusion and sampling is available at *PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE*

 An Important message 

 *Overindulging in NIPT (Cell free DNA) after an Increased NT in first trimester can invite a future trouble* 

Let’s understand the concept with a recent case of Increased NT sent to _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ (follow the link below for committee opinion of ACOG about the same)

A Clinical and Genetical low risk primi of 29 years was referred to our centre for a Level II scan at 19+3 weeks. At First trimester, she was found to have an *increased NT (At other centre) with normal Dual markers (PAPP-A & B-HCG* ). She was advised *NIPT by her doctor which showed LOW RISK for Trisomy 21, 18 & 13).* While doing Detailed anatomical surveillance Ultrasound (Level II), *we detected TGA ( Transposition of great arteries* ) .

Now what to do?? Remember she is 19+3 weeks.

 *Concept number one* : 

 *In every case of Increased NT, Think beyond Down syndrome (or Edward or Patau* ). NIPT only caters *five* chromosomes *(21, 18, and 13, X, Y).* It doesn’t deal with rest and also *cannot* assess the risk for *fetal anomalies like ventral wall defects and neural tube defects* 

An *increased NT* can also be seen in _cardiac defects, diaphragmatic hernia, exomphalos, body stalk anomaly, skeletal defects, and certain genetic syndromes, such as congenital adrenal hyperplasia, fetal akinesia, deformation sequence, Noonan syndrome, Smith-lemli-Opitz syndrome and spinal muscular atrophy._ 

 *Concept number two* : 

As at PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE, We offer genetic counselling and detailed ultrasound evaluation at 15 to 16 weeks so that above stated anomalies can be ruled out and confident decision about *Amniocentesis (with full karyotype and Micro-Array) versus NIPT (Only Five Chromosomes* ) can be made as still we have four weeks in hand for any termination if required. *In both the cases, however a further detailed ultrasound at 19 weeks and a fetal echocardiography is recommended too* .

 We must proudly emphasise here that while doing NT Scan, We always look for above stated problems that potentially could lead to Increased NT.

So in conclusion NIPT is part of the puzzle, but it is not the whole picture. A comprehensive approach that combines NIPT with a series of ultrasounds and other screening tests based on the patient’s risk factors can provide the optimal combination of effective prenatal care and patient peace of mind.

https://www.acog.org/-/media/Committee-Opinions/Committee-on-Genetics/co640.pdf?dmc=1

 *Case Discussion* :

 _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ 

 *PPROM* at *19 weeks* and role of *Ultrasound guided Amnio Infusion* and *Fibrin Sealants*

This Patient, Conceived with IVF, Had a leak at 19 weeks with *Absolute Anhydraminos on Ultrasound,* However She was  free from any clinical signs of overt chorioamnionitis like infection, fever, increased C reactive protein (CRP), white blood cells and uterine tenderness. Detailed informed counseling regarding the potential *risks (chronic oligohydramnios, potter facies, club feet and pulmonary hypoplasia with universal moderate pulmonary artery hypertension)* and benefits of continuing pregnancy and about the procedure was done. 

Under Strict Aseptic Precautions, *Ultrasound Guided Amnioinfusion* was done with 20 guage spinal needle, slowly avoiding any contact with fetus or cord and  Normal saline was transfused  till vertical pocket increased to 5 cm. Patient was made to rest and discharged . *If the leaking persisits, Patient is advised to come back for Cryoprecipitate infusion.* 

 *Rationale of Treatment* :

 *1.Ultrasound Guided Amnioinfusion* :

 *a)* Obviously would immediately increase AFI.

 *b)* The immediate expansion of amniotic cavity would plaster the broken hole of amnion-chorion to the uterine wall, thereby blocking the potential leak.

 *c)* Apt Fluid hence would let fetus to move freely leading to decrease chances of potential strictures, Hypoplasia, Deformities etc

 *d)* A good AFI is must for an Ultrasound for anatomical surveillance (Level- II), Especially for Foetal urogenital area

 *2 *.Fibrin Sealents/Amniopatch* ( Esp in PPROM)

 It is supported by the fact that the infusion of platelets followed by cryoprecipitate provides fibrinogen, fibronectin, platelet derived growth factors, TGF-beta, von Willebarnd factor, factor VIII and factor XIII in high concentrations, which adhere to the area of leak in amnion and chorion forming a platelet plugs which is subsequently stabilized by cryoprecipitate

Other Treatments offered In cases with *Idiopathic Oligohydraminos* are:

 *1. Maternal Hydration (Oral/Intravenous* )

 *Rationale* : Maternal osmotic change and/or maternal volume expansion would probably bring a positive osmotic gradient towards the amniotic cavity thereby increasing AFI.

 *2. Amino acids (Arginine) (Oral /Intravenous)* 

 *Rationale:* l-arginine is the sole endogenous precursor of nitric oxide (NO) which is involved in the regulation of blood flow in vascular beds ,causes vasodilatation and shows aggregative effect on platelets which  increases the volume and viscosity of blood  in the fetomaternal circulation

 *3.Slidenafil/Aspirin/Heparin/Progesterone/Vassopressin*

 *Rationale*: These all would improve the compromised uteroplacental circulation and hypoperfusion in one way or the other and hence improve AFI

 *PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE* 

302, DEFENCE COLONY NEAR BUS STAND,

JALANDHAR

*Ever Wondered* 

*Why Nuchal Translucency scan is offered between 11 to 13+6 weeks of Gestation and not Before or After* 

 _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ brings you the details….

There are *two reasons* for selecting 11 weeks as the earliest gestation for measurements of NT.

1. As the Fetus is growing, *Many major fetal areas appear clealy only after 11 weeks* (For Example)

 *a)  Ossification of the fetal skull is not reliable before this gestation* and hence one can miss Diagnosis or exclusion of *acrania* and therefore *anencephaly* If done before 11 weeks.

 *b)* Examination of the *four-chamber view of the heart* and main arteries is possible only after 10 weeks.

 *c)* There is a *normal herniation of the midgut* that is visualized as a hyperechogenic mass in the base of the umbilical cord before 10 weeks  and it is therefore unsafe to diagnose or exclude *exomphalos* at this gestation.

 *d)* The *fetal bladder* can be visualized in only 50% of fetuses at 10 weeks, in 80% at 11 weeks and in all cases by 12 weeks. 

 *2.*  In cases which come positive and further need a diagnostic Invasive procedures , *chorionic villous sampling before this gestation is not recommended as it is associated with transverse limb reduction defects.*

The reasons for selecting *13 weeks and 6 days* as the upper limit is to:

1. Provide women with affected fetuses the option of *first rather than second trimester termination.* 

 *2* . The incidence of abnormal accumulation of nuchal fluid in chromosomally abnormal fetuses is *lower at 14–18 weeks than before 14 weeks* 

 *3* . The fetus *becomes vertical after 14 weeks* making it more difficult to obtain the appropriate image.

 *PROMISE* *ULTRASOUND AND FETAL MEDICINE CENTRE* 

 *302, DEFENCE COLONY*

 *NEAR BUS STAND* 

 *JALANDHAR*

*Dr Jyotsna* of _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ is *specially trained in 4D Fetal echocardiography* and Fetal Invasive procedures.

Lets discuss in brief about Fetal Echocardiography and it’s indications *(especially where we miss to offer it to our patients)* 

Fetal echocardiography is a  specialized

diagnostic procedure which basically is  an *extension of The classic Four chamber view and outflow tracts* seen in routine Level II scan.Congenital heart disease is a *leading cause of infant morbidity and mortality* from birth defects

with an estimated incidence of 6 per 1000 live births for moderate to severe forms

Although there are specific indications, *we usually  miss to offer Fetal echocardiography in following situations* 

 *1.* *IVF pregnancy*  Always offer a separate Fetal echo in IVF cases according to AIUM guidelines.This probably is because gametes are externally manipulated with exposure to so much media or because IVF itself is a high risk pregnancy.

 *2.Diabetes stuck pregnancy* as diabetes has a strong known association with VSD,truncus arteriosus,TOF,TGA etc

 *3.Abnormal Nuchal translucency scan or  prenatal screening/markers* ….Although in all cases with increased NT, Fetal Echo should be done according to AIUM guidelines,We at _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ recommend the same for other positive prenatal Screening tests as well

 *4.Any Accidental clinical Finding of Fetal bradycardia or dysthymia on auscultation* 

 *5.Suspected Unknown teratogenic exposure in first trimester* 

Other  Indications are:

• Autoimmune antibodies, anti-Ro (SSA)/anti-La (SSB);

• Familial inherited disorders (eg, 22q11.2 deletion syndrome)

• Abnormal cardiac screening examination

• First-degree relative of a fetus with congenital heart disease

• Fetal chromosomal anomaly

• Extracardiac anomaly

• Hydrops

• Monochorionic twins

Dear Doctor,

You must have noticed that while doing *First Trimester Ultrasonography* for various reasons, _PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE_ always report *Uterine Artery Doppler Parameters* . Let’s briefly discuss the Importance of the same in First Trimester.

Doppler in second and third trimester is not new to anyone. There is a growing evidence that first-trimester uterine artery Doppler has better predictive accuracy in detecting *early-onset preeclampsia and Fetal Growth Restriction* than late-onset disease. Although The sensitivities and specificities of uterine artery Doppler is moderate (40%) which limits its utility as a disease marker in isolation but associating Doppler with other multiparametric models like *maternal characteristics  and biochemical markers*  have the potential to improve detection rates for preeclampsia and other adverse pregnancy outcomes to *over 90%.* 

The biochemical markers used in First trimester  screening for Preeclampsia and FGR are *PAPP-A, PlGF, sFLT-1, Inhibin-A, Activin-A, sEng, PP13, ADAM12* etc.

Maternal characteristics that associate the most are *BMI, Ethnicity, parity, previous PE, age, HTN, DM, Renal Disease, thrombophilia and smoking .* 

So in conclusion, A Well Studied Ultrasound in first trimester  can tell you a lot of things other than Fetal well being ,Chorionicity and Multiplicity….

1. *As an aneuploidy scan* , Nuchal translucency with Nasal bone, tricuspid flow, ductus venosus flow ,maternal age and PAPP-A and HCG, it can Detect for Down’s Syndrome with an accuracy *of 95%* 

2. *As a chance to screen for Preeclampsia and IUGR* ,As mentioned above with an accuracy *of 95%* 

3. *As a Anomaly scan* with Detection rate of *100 %* for some abnormalities like Anencephaly,Holoprosencephaly etc and *50%* in some others. 

 *PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE*

Two most frequently encountered dilemmas in routine

*First trimester* 

 In cases with *enlarged* *nuchal* *translucency* , not only Aneuploidy risk increases but it can also be associated with *Noonan syndrome, multiple pterygium syndrome, skeletal dysplasias, congenital heart disease, and other anomalies.* 

 *MANAGEMENT:* 

For patients with increased NT, We at Promise Ultrasound and fetal medicine centre do an *early Detailed anatomical/Structural Surveillance* . If No Structural abnormality is seen, we offer Cell Free DNA (cfDNA/NIPT), *But in cases where structural Anomaly is found, we prefer to do Amniocentesis with Micro array rather than a just Karyotype* .

*Second trimester*:

 Any isolated finding Like:

*a)  Pyelectasis* ( Renal pelvis measuring ≥ 4 mm in anteroposterior diameter up to 20 weeks of gestation)

*b) Echogenic intracardiac foci* ( Echogenic tissue in one or both ventricles of the heart seen on standard four-chamber view )

*c) Echogenic bowel* (Fetal small bowel as echogenic as bone )

*d) Thickened 2nd Trimester nuchal fold* ( ≥ 6 mm from outer edge of the occipital bone to outer skin in the midline )

*e) Mild ventriculomegaly* ( Lateral ventricular atrial measurement between 10–15 mm )

*f) Choroid plexus cysts* (Discrete cyst(s) in one or both choroid plexus(es)

*g) *Short femur length** (Measurement < 2.5 percentile for gestational age)

*Management*:

*A proper Genetic Counselling* with *Aneuploidy sceening*( If missed early) along with Second-trimester *detailed anatomic survey* is a must. *Fetal echocardiography* too is indicated in most of these cases.Testing for *Cytomegalovirus* is indicated in echogenic bowel and ventriculomegaly.A *repeat ultrasonography* for potential IUGR and Urinary Obstruction might also be needed in some.

*PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE*

Case Discussion: Holoprosencephaly*

A  28 year old *Primigravida referred to Promise Fetal Medicine Centre for NT scan at 11+3 weeks with no relevant medical or genetic history.* While performing Ultrasound, *Axial section of the head  revealed the presence of a single sickle shaped ventricle with fused thalami and absence of  characteristic Butterfly shaped choroid plexus in transverse section* ( Follow picture).

A diagnosis of Alobar variety of Holoprosencephaly was made. No other abnormality was detected. *Chorionic villus sampling was done and patient proceeded for termination after proper counselling.*

*What is Holoprosencephaly* ? 

Holoprosencephaly is an abnormal development of brain which starts at 6 weeks of embryonic period. It results from Failure of the brain to divide in left and right halves thereby forming a single primitive monoventricle along with fused basal ganglia, absence of corpus callosum and falx cerebri. Other findings which are associated with Holoprosencephaly are: facial anomalies like cleft lip and palate, eye anomalies, nasal abnormalities, renal anomalies, polydactyly, cardiovascular anomalies and omphalocoele.

 *How bad is the problem?* 

Most of the foetuses die  intrauterine only and  a few which are born would die in early neonatal period as the defect is associated with severe life threatening anomalies  .Overall if diagnosed the prognosis is grave and termination is the best course.

 *Why did it happen?* 

Most commonly (25-50%) are due to chromosomal problems  with Trisomy 13 being most common apart from Trisomy 18, partial Trisomy 13 and triploidy. Environmental (Diabetes), maternal alkaloids intake, radiation exposure, salicylate, methotraxate,retinoids intake have shown some association with Holoprosencephaly.

For sporadic Non-Chromosomal Holoprosencephaly, The risk of empirical recurrence is 6%. It can be part of genetic syndrome when no chromosomal association is found.

*How to diagnose it and what is the management* *?*

Alobar Holoprosencephaly is diagnosed in first trimester (i.e. during anatomical evaluation at the time of NT/NB) with close to 100% accuracy. Transverse view (with the presence of a single sickle shaped ventricle with fused thalami and absence of the characteristic Butterfly shaped choroid plexus) provide the diagnosis. It must be remembered that although termination is advised, a Fetal invasive procedure (CVS) with Appropriate Genetic test before termination would help us to *prognosticate* the next pregnancy as the *recurrence risk in subsequent pregnancies is 1 percent if it is due to a genetic  abnormality and much higher(33%)*  if either parents are carriers of a balanced translocation. If either parent has some phenotypic abnormality it could indicate an *autosomal dominant form with a recurrence risk as high as 50%.*

*Conclusion* :

*1*  *Defects like Holoprosencephaly can be diagnosed with fair accuracy in the first trimester itself during NT/NB.*

*2*  *Termination of pregnancy is the final management* .

*3*  *Fetal invasive procedure (CVS)/ Amniocentesis with Appropriate Genetic test (MicroArray preferred or minimum Karyotype ) should be offered before termination in all cases as it helps to prognosticate the next pregnancy and provide the couple with the chances of recurrence* .

*4*  *Prenatal Genetic tests are superior to post natal as culture failure rate is much higher ( 20% in post natal samples). It can be the result of improper specimen collection or transport, improper laboratory technique, or the condition of the sample* .

Case Discussion* 

*Selective Fetal reduction in Twins with one fetus discordant for Structural or Chromosomal Anomaly*

A 28yrs Primigravida presented at 12.3 weeks for  NT/NB scan and was found that she was bearing  a *dichorionic twin pregnancy with one fetus having septated cystic hygroma with omphalocoele*  . Rest markers and morphology for this affected  fetus and other fetus were absolutely  normal . *She was planned for Chorionic Villous Sampling of both foetuses* *after detailed genetic counselling  with selective reduction of anomalous foetus*

i.e. foetus with above said defects. Patient followed the advice and Selective reduction of the anomalous fetus was successfully done.

We all know that multifetal pregnancies (Triplets and beyond) can be reduced to twins for one simple reason that it improves the perinatal and obstetrical outcome.

*The other lesser known indication where fetal reduction might be of a help is when one of the twin is carrying a structural or genetic anomaly and other foetus is absolutely normal.*

*In this broadcast, PROMISE ULTRASOUND AND FETAL MEDICINE CENTRE discusses the issues related to selective feticide of foetuses with major or lethal abnormalities.*

 *Question 1: Compared to singleton, do twins carry more chances of being genetically or structurally abnormal?* 

It must be kept in mind that Compared to women with a single pregnancy, women with a twin pregnancy *have increased chances of carrying one foetus with a structural abnormality.* Also due to the rapid and ongoing advancements in prenatal diagnosis and screening , these abnormalities are now being diagnosed at an earlier gestation. This has lead to a Consequence, where more and more obstetricians are facing the circumstances of a twin pregnancy with one abnormal foetus i.e. DISCORDANT FOR ANOMALY twins.

Compared to Dizygotic (DZ) twins, the frequency of malformations in Monozygotic (MZ) pairs has been reported to be 2-3 times higher.

Obviously  Structural or developmental malformations can occur in any twin independent of the zygosity but  chromosomal malformations if present theoretically should occur in both twins in monozygotic pairs as they arise from a common gene pool or embryo, but again it’s not a rule. Remember chromosomal malformations too have been reported in one fetus of monozygotic due to post zygotic gene modification. *Hence sampling of both fetuses is highly advisable*

 *Question 2:  What is the next mode of action after such a situation arises?* 

As soon as the dilemma of discordant anomaly arises proper evaluation of both twins including echocardiography and counselling  regarding the antenatal and postnatal issues and outcome is required. Prognosis and recurrence risk are discussed. Approximately 1–2% of twin pregnancies may face the dilemma of expectant management versus selective termination following diagnosis of an anomaly affecting only one fetus.

*Question 3: Expectant management versus selective feticide?* 

In expectant management the pregnancy continues as such in view of ascertaining best perinatal outcome for the normal fetus. *It has published in various international studies that  The presence of a fetus with a major anomaly in a twin gestation increases the risk of preterm delivery, low birth weight and perinatal mortality of the normal co-twin.* This gave the concept of selective fetal reduction.

The second concern obviously is about the optimum gestational age at which the termination is to be performed. Classically in modern era, Elective multifetal reduction to twins is *done at 11-13 weeks after assessing Nuchal translucency and other potential markers.* *Some professionals advocate doing it at 13-15 weeks so that an early detailed anatomical scan can also be incorporated,* Thus reducing the chance of leaving a genetically or structurally abnormal child

*However in some cases where an abnormality is detected late (for example at 22 weeks, one fetus having AVSD with DORV with other being fine), Reduction raises a lot of legal and ethical issues.*

*Remeber late reductions are associated with increased chance of miscarriage or preterm delivery and hence in these cases, some professionals advocate (debatable) to reduce at the age of viability of foetus (generally 28 weeks, subject to legal boundaries).*

*Does type of twin affect the reduction technique?*

If the option of selective fetocide is considered, the main variable determining the technique to achieve this aim is chorionicity. In a dichorionic pregnancy, passage of substances from one twin into the circulation of the co‐twin is unlikely due to the lack of placental anastomoses, hence KCl can be injected safely into the circulation of the affected twin to produce fetal asystole.

In monochorionic twin pregnancies, selective termination needs to be performed by ensuring complete and permanent occlusion of both the arterial and venous flows in the umbilical cord of the affected twin, in order to avoid acute haemorrhage from the co‐twin into the dying fetus, which may lead to death or organ damage. Bipolar cord coagulation under ultrasound guidance is associated with approximately 70–80% survival rates.

*Conclusion:* *Selective  Fetal reduction is a reasonably good  option in twins with one  structurally or chromosomally or early onset severe TTTS.*