Fetal Medicine Center Research Articles

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

Uromodulin: a new biomarker of fetal renal function?

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Perinatal Outcome after Multifetal Pregnancy Reduction: A Retrospective Analysis of 1-year Data in a Referral Fetal Medicine Center

ABSTRACT Aims Multiple pregnancies are associated with higher maternal and perinatal morbidity and mortality. Multifetal pregnancy reduction is an accepted method to reduce the morbidity associated with higher order multiples. The present study describes the perinatal outcome of 336 pregnancies which underwent multifetal reduction in our center. Materials and methods This is a retrospective descriptive study of all patients who underwent multifetal pregnancy reduction during the period from September 1, 2010 to August 31, 2011. The demographic details of the patients were extracted from the Sonocare software database. Fetal reductions were performed using standard protocols after a detailed structural evaluation including nuchal translucency. The perinatal outcome was obtained from hospital records or from patients over telephone. Results Of the total 336 pregnancies, 21% were lost to follow-up. The remaining 265 were analyzed for the perinatal outcome. The take home baby rate was 80.2%. Total fetal loss rate was 11.6% and partial pregnancy loss rate was 3.8%. Mean gestational age at delivery was 34.7 weeks. A total of 22.1% of women delivered at term. A total of 34.5% of the patients had late preterm delivery (35—37 weeks). The mean birth weight was 2002 gm. Conclusion The data shows that the outcomes of multifetal pregnancy reduction in India are similar to published data from other countries, with a good perinatal outcome in over 80% cases. However, the data also points to the urgent need for stringent guidelines for ovulation induction and embryo transfer to reduce the requirement for and number of these procedures in the future. How to cite this article Latha PM, Andrew C, Suresh I, Seshadri S. Perinatal Outcome after Multifetal Pregnancy Reduction: A Retrospective Analysis of 1-year Data in a Referral Fetal Medicine Center. J South Asian Feder Obst Gynae 2016;8(4):266-270.

Relationship of Fetal Complications in Monochorionic Diamniotic Twin Pregnancy with Placental Site Cord Insertion: A Retrospective Analysis of 30 Months Data in a Referral Fetal Medicine Center

ABSTRACT Aims Among the increasing twin gestations, monochorionic twins occur in about 12 to 15% of all twin gestations and the occurrence is about 1 in 20 in assistive reproductive technology pregnancies. Early detection of twin to twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) aids the obstetrician in counseling and therapy as required. Materials and methods This is a retrospective cohort study of monochorionic diamniotic (MCDA) pregnancies referred from January 2011 to June 2013. Those cases that had crown rump length and nuchal translucency measurements done in the first trimester and then at least one subsequent scan at > 16 weeks, at the institution were chosen. The objective was to assess the utility of placental site of cord insertion in early second trimester scan to predict fetal outcome in monochorionic twin pregnancy. The patient characteristics, placental cord insertion site, and neonatal outcomes were compared among TTTS, sIUGR, and normal groups. Discussion Of 89 MCDA pregnancies, only 60 had been referred for second trimester scan. Among these, in 48 (80%) of pregnancies, both babies were delivered and discharged alive and well. Cord insertions that were eccentric or central were classified as “type A”. Marginal and velamentous cord insertions were classified as “type B”. Pregnancies with both types A and B insertions were called “concordant cord insertions group” and the others were classified as “discordant cord insertions” group. The two groups were compared to look for the pregnancy complications — TTTS or sIUGR. Results The concordant cord insertions (n = 33) had 84.8% of pregnancies having a normal pregnancy and 12.1 and 3.1% developing sIUGR and TTTS respectively. The discordant cord insertion group (n = 27) had 59.2% with normal findings at the second scan and 14.8 and 26% developing sIUGR and TTTS respectively. The incidence of TTTS was 30% in twin pairs with discordant cord insertions and 3% in twin pairs with concordant cord insertions (p = 0.0158). Cord insertions did not influence the occurrence of sIUGR in our study. (p = 0.69). Significantly more pregnancies with concordant cord insertions had normal outcomes (p = 0.02). Conclusion Determination of placental site of cord insertion should be incorporated into protocols of twin pregnancy care. This is a window of opportunity to gain valuable information regarding the pregnancy. Further large studies incorporating fetal biometric and Doppler parameters could show the relative utility of each parameter in the detection of MCDA vascular complications. If the MCDA pregnancy can be classified as “low risk” then reassessment intervals can be extended. This would help to reduce patient stress and costs involved in repeated scans. How to cite this article Andrew C, Suresh I, Seshadri S. Relationship of Fetal Complications in Monochorionic Diamniotic Twin Pregnancy with Placental Site Cord Insertion: A Retrospective Analysis of 30 Months Data in a Referral Fetal Medicine Center. J South Asian Feder Obst Gynae 2016;8(4):304-308.

Prenatal interventions for congenital diaphragmatic hernia for improving outcomes.

Prenatal interventions for congenital diaphragmatic hernia for improving outcomes.

Chorionic Villus Sampling in Assisted Versus Spontaneous Conception Twins

Purpose To compare the outcome of chorionic villus sampling (CVS) in twin pregnancies following assisted reproduction technology (ART) versus twins that have been conceived spontaneously. Materials and Methods Retrospective analysis of dichorionic twin pregnancies that underwent CVS between 1986 and 2013 at our department which is a tertiary center for fetal medicine. 32 twin pregnancies after ART and 130 spontaneously conceived twin pregnancies, which underwent CVS, were analyzed. Results No difference was observed in the pregnancy loss rate between the two groups (0 % in the ART group vs. 3 % in the spontaneous twins group). The rate of preterm delivery before 28 weeks was higher in the ART group (18.8 %) compared to the control group (1.6 %). The perinatal mortality rate was similar in the two groups. Conclusion The pregnancy loss rate following CVS is similar in ART twins and in spontaneous twins. However, the risk of prematurity before 28 weeks is significantly higher in the ART group.

Middle cerebral artery peak systolic velocity to predict fetal hemoglobin levels in twin anemia-polycythemia sequence.

To evaluate the diagnostic accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) Doppler measurements in prediction of hemoglobin levels in twin anemia-polycythemia sequence (TAPS). This study involved a consecutive cohort comprising monochorionic twin pregnancies complicated by TAPS managed at three European fetal medicine centers between 2005 and 2013. The accuracy of MCA-PSV, measured immediately prior to fetal hemoglobin (Hb) measurement by fetal or cord blood sampling, for prediction of anemia and polycythemia was assessed using 2 × 2 tables. A total of 116 measurements (74 recorded in donors and 42 in recipients) from 43 twin pregnancies complicated by TAPS were available for analysis. MCA-PSV multiples of the median (MoM) values correlated well with Hb levels (r = - 0.86; P < 0.001). The sensitivity of MCA-PSV ≥ 1.5 MoM to predict severe anemia (Hb deficit > 5 SD below the mean) in TAPS donors was 94% (95% CI, 85-98%); specificity was 74% (95% CI, 62-83%); positive and negative predictive values were 76% (95% CI, 65-85%) and 94% (95% CI, 83-98%), respectively. The sensitivity of MCA-PSV ≤ 1.0 MoM to predict polycythemia (Hb level > 5 SD above the mean) in TAPS recipients was 97% (95% CI, 87-99%); specificity was 96% (95% CI, 89-99%); positive and negative predictive values were 93% (95% CI, 81-97%) and 99% (95% CI, 93-100%), respectively. MCA-PSV measurement has high diagnostic accuracy for predicting abnormal Hb levels in fetuses with TAPS.

First Trimester Diagnosis of Congenital Heart Disease

A 26-year-old primigravida came to our Fetal Medicine Center for first trimester aneuploidy screening at 13 weeks. Ultrasound was done using Voluson E8 (GE Healthcare , Milwaukee, WI, USA) with convex abdominal 4–8 MHz transducer and transvaginal 15–20 MHz transducer. On abdominal imaging, there was cardiomegaly with tricuspid regurgitation. On transvaginal scan, clear cardiac disproportion with a small left atrium and ventricle were seen (Fig. 1). On application of color Doppler, the flow across the mitral and aortic valves was negligible with hyperdynamic flow on the right side with tricuspid regurgitation (Figs. 2, 3). Foramen ovale was opening on the right side and the flow in the arch of aorta was reversed. Fig. 1 An axial image of the fetal chest on transvaginal sonography at 13 weeks showing a grossly-enlarged heart with a clear ventricular disproportion (Right[[[Left)

Outcome of Antenatally Diagnosed Cardiac Rhabdomyoma: Case Series from a Tertiary Fetal Medicine Center in India

AbstractThe aim of this case series is to review our institution’s experience with fetal cardiac rhabdomyoma, to document the clinical outcome and the incidence of associated tuberous sclerosis (TS) in these babies after birth. Eight cases with fetal cardiac rhabdomyoma were studied over a period of three years and the perinatal outcome was obtained. Out of these eight cases diagnosed antenatally, seven pregnancies continued till term and one woman opted for termination of pregnancy. There was one early neonatal death and of the six living, five developed TS with cutaneous and neurological manifestations. This association is similar with other larger multicentric studies and meta-analysis. Fetal cardiac rhabdomyoma is strongly associated with the development of TS in postnatal life, and the couples should be counseled regarding this association.

Fetal Intracardiac Transfusions in Hydropic Fetuses with Severe Anemia

Introduction: Fetal anemia can have significant perinatal morbidity and mortality, particularly with onset prior to 20 weeks of gestation. Materials and Methods: We detail a case-cohort study (n = 8) of all women who underwent fetal in-utero, intracardiac transfusion prior to 24 weeks of gestation (7 women before 20 + 1 weeks), between March 2004 and September 2014, in a supraregional Fetal Medicine Center in the United Kingdom, comprising 2.2% of all transfusions performed during this period. All the fetuses were hydropic, with high maternal BMI, and had severe anemia as an indicator for transfusion. It was an attempt to perform intravascular transfusion when other common routes of fetal vascular access had failed. Results: There were 2 intrauterine deaths (25%), both of which were associated with in-utero transfusion and fulminant parvovirus B19 infection. The perinatal survival rate was 75% (6/8). Discussion: Fetal in-utero, intravascular transfusion by the intracardiac route may be used to correct severe early-onset anemia. It is particularly useful when technical issues of fetal size, early gestation (<20 weeks), maternal adiposity, and hydrops fetalis make umbilical cord or intrahepatic vein puncture technically difficult. Survival rates appear comparable to other series of pregnancies where in-utero transfusion is performed at early gestation.

Risk assessment for preeclampsia in nulliparous women at 11-13 weeks gestational age: prospective evaluation of two algorithms.

To evaluate two algorithms for prediction of preeclampsia in a population of nulliparous women in Norway. Prospective screening study. National Centre for Fetal Medicine in Trondheim, Norway. Five hundred and forty-one nulliparous women. The women were examined between 11(+0) and 13(+6) weeks with interviews for maternal characteristics and measurements of mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A and placental growth factor. The First Trimester Screening Program version 2.8 by The Fetal Medicine Foundation (FMF) was compared with the Preeclampsia Predictor TM version 1 revision 2 by Perkin Elmer (PREDICTOR). Prediction of preeclampsia requiring delivery before 37 weeks, before 42 weeks and late preeclampsia (delivery after 34 weeks). The performance of the two algorithms was similar, but quite poor, for prediction of preeclampsia requiring delivery before 42 weeks with an area under the curve of 0.77 (0.67-0.87) and sensitivity 40% (95% CI 19.1-63.9) at a fixed 10% false positive rate for FMF and 0.74 (0.63-0.84) and sensitivity 30% (95% CI 11.9-54.3) at a fixed 10% false positive rate for PREDICTOR. The FMF algorithm for preeclampsia requiring delivery <37 weeks had an area under the curve of 0.94 (0.86-1.0) and sensitivity of 80% (95% CI 28.4-99.5) at a 10% fixed false positive rate. Fetal Medicine Foundation and PREDICTOR algorithms had similar and only modest performance in predicting preeclampsia. The results indicate that the FMF algorithm is suitable for prediction of preterm preeclampsia.

Reassessing critical maternal antibody threshold in RhD alloimmunization: a 16-year retrospective cohort study

To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization. This was a retrospective cohort study, covering a 16-year period at the national tertiary fetal medicine center for management of alloimmunization. Data concerning RhD alloimmunized pregnant women were extracted from an institutional database and maternal anti-D antibody levels were cross-checked with the national reference laboratory. Fetal hemoglobin (Hb) levels were determined only at the first intrauterine transfusion (IUT) and were compared with the pretransfusion maternal anti-D antibody level (IU/mL). Sensitivity, specificity and positive and negative predictive values of maternal antibody thresholds for detecting moderate to severe (Hb ≤ 0.64MoM) fetal anemia were calculated. Between 1996 and 2011, 66 women underwent a first IUT for RhD alloimmunization at our institution. The highest serum anti-D antibody level was extracted for 208 RhD alloimmunized women who did not require IUT during the last 10 years of the study period. The traditional maternal antibody threshold of > 15 IU/mL failed to detect 20% of cases of moderate to severe fetal anemia. The ≥ 4 IU/mL threshold had 100% sensitivity but a 45% false-positive rate. The optimal anti-D antibody threshold for specialist referral in our population was ≥ 6 IU/mL; at this level, no case of moderate to severe anemia was missed and specificity was 61%. Use of this threshold would have eliminated 10% of referrals to our fetal medicine unit without compromising fetal outcomes. Setting the critical maternal RhD antibody level at >15 IU/mL does not provide sufficient sensitivity. The lower threshold of ≥ 4 IU/mL, though sensitive, is associated with a 45% false-positive rate. In our population, a threshold of ≥ 6 IU/mL minimizes false-positive referrals while maintaining 100% sensitivity for moderate to severe fetal anemia.

A prospective study of screening for hypertensive disorders of pregnancy at 11-13 weeks in a Scandinavian population.

To investigate the prediction of preeclampsia and gestational hypertension using maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at gestational weeks 11-13 in a Scandinavian population with a medium to high prior risk for developing hypertensive disorders of pregnancy. Prospective screening study. National Center for Fetal Medicine, Trondheim, Norway. 579 women who were nulliparous or had a previous history of preeclampsia or gestational hypertension. Women were examined between 11(+0) and 13(+6) weeks, with interviews for maternal characteristics and measurements of MAP, UtAPI, PAPP-A and PlGF. The tests were evaluated separately and in combined models with receiver operating characteristics (ROC) curves. Prediction of preeclampsia, severe preeclampsia and gestational hypertension. The best model for severe preeclampsia (MAP+UtAPI+PlGF+PAPP-A) achieved an area under the ROC curve of 0.866 [95% confidence interval (95% CI) 0.756-0.976]. The best models for preeclampsia (MAP+UtAPI+age) achieved 0.738 (0.634-0.841), gestational hypertension (MAP) 0.820 (0.727-0.913) and hypertensive disorders in pregnancy overall (MAP+PlGF+age) 0.783 (0.709-0.856). Using the best model we could identify 61.5% (95% CI 31.6-86.1) of severe preeclampsia, 38.5% (95% CI 20.2-59.4) of preeclampsia and 42.9% (95% CI 21.8-66) of gestational hypertension at a fixed 10% false-positive rate. Maternal characteristics, MAP, UtAPI, PAPP-A and PlGF showed limited value as screening tests. Further research on biochemical and biophysical tests and algorithms combining these parameters is needed before first trimester screening for hypertensive disorders of pregnancy is included in antenatal care in Scandinavia.

P21.09: Improving outcome of in utero fetal transfusion by increasing the target fetal hematocrit

Improve fetal outcome and reduce the number of fetal intervention after Rh alloimmunization by reducing the number of inutero transfusion by increasing the target fetal hematocrit. Rh alloimmunization is common in India and western world. To improve the outcome and make it available across the country, we have tried many strategies. One of them is to reduce the number of Inutero transfusion by increasing the target fetal hematocrit to 55 % rather than standard 45%. Other aims are to reduce the over all cost of the IUT so that many more people will be able to afford it. We have analyzed the data of our center (Paras Advanced Center for Fetal Medicine, Ahmedabad, India) between January 2008 to December 2013. We retrospectively analyzed 314 fetal transfusions and found better fetal outcome with this strategy - Group A -74% v/s Group B 86 % (Group A -45% target v/s Group B - 55 %). Over all 21% fetal transfusion rate was reduced. Complications and cost related to IUT was also reduced. While doing inutero fetal transfusion procedure, target of fetal hematocrit should be increased from 45% to 55% ( 20% Approximately). Over all procedure rate and complication rate was reduced and fetal outcome is also improved. Long-term outcome up to 3 years shows NO difference in outcome between 2 groups.

P05.12: Diagnosis of fetal structural abnormalities at the 11–14 week scan in a tertiary Fetal Medicine Unit

Ultrasound (US) exam in the first trimester allows the detection of many malformations, dysplasias, deformations and genetic syndromes, besides screening for chromosomal anomalies using classical markers as nuchal translucency (NT), ductus venosus and nasal bone. A total of 8783 pregnant women referred to a tertiary Fetal Medicine Center between 11 and 13 6/7 weeks of gestation were submitted to an US exam, including anatomy study and measurement of NT and other ultrasound markers for trisomies. All patients were followed until delivery, when the sonographic findings were compared to the clinical and/or pathological findings. Isolated abnormal NT were not included. First trimester scans detected 231 structural anomalies (2,9%), and 29,6% of the total defects. Most frequent diagnosis were: acrania/exencephaly, hidropsy, cystic hygroma, bladder outlet obstruction, omphalocele, gastroschisis, holoprosencephaly and Body-Stalk anomaly. First trimester US screening has a very good potential for detection of fetal structural abnormalities, but the second trimester US screening remains important to improve prenatal care.

The challenges of interventional trials in fetal therapy

Fetal therapy is an advancing specialty but the assessment of effectiveness for many therapies has been limited to observational data1 ,2 with randomised controlled trials (RCTs) employed with varying success.3...

Biparietal diameter-to-crown-rump length disproportion in first-trimester fetuses with holoprosencephaly.

To determine whether the biparietal diameter measurement is altered in first-trimester fetuses with holoprosencephaly. Cases of holoprosencephaly were collected retrospectively from 4 fetal medicine centers, and first-trimester biparietal diameter measurements were reviewed. The diagnosis of holoprosencephaly was established sonographically by the detection of abnormal choroid plexus morphologic characteristics (absent "butterfly" sign) and the identification of a monoventricular cerebral cavity on axial views of the fetal brain. The proportion of fetuses with biparietal diameter measurements below the 5th percentile for crown-rump length was determined. Among 45 cases of holoprosencephaly reviewed, 43 had information on both biparietal diameter and crown-rump length measurements. The biparietal diameter was below the 5th percentile for crown-rump length in 14 (32.6%) fetuses. Chromosomal analysis was available in 41; no statistically significant difference in biparietal diameter measurement between those with associated chromosomal anomalies and those without anomalies was noted. A supplementary analysis using head circumference measurement showed an even greater proportion of fetuses with holoprosencephaly with measurements below the 5th percentile for crown-rump length (18 of 42 [42.9%]). One-third of first-trimester fetuses with a sonographic diagnosis of holoprosencephaly had a biparietal diameter that was smaller than expected for crown-rump length. In this subset of fetuses, the evaluation of intracranial anatomy for signs of holoprosencephaly may be more difficult to perform due to the smaller size of the brain. Therefore, the detection of a biparietal diameter below the 5th percentile as expected from crown-rump length on the first-trimester scan may be a warning sign of holoprosencephaly and should prompt a detailed examination of the intracranial anatomy.

PFM.51 Fatal transfusion-associated graft vs host disease (TA-GvHD) following emergency intrauterine transfusion of maternal blood: case report and survey of UK practice

For intrauterine transfusion (IUT) specific red cells are provided by UK Blood Services, irradiated to prevent TA-GvHD.A fetus (21/40) was referred to a fetal medicine centre (FMC), severely anaemic (parvovirus)...

PA.10 When is low risk not low risk?

BackgroundThe current Down’s screening programme has the potential to identify pregnancies at risk of other significant chromosomal problems. However unless at increased risk for trisomy 21 these pregnancies are usually...

PB.08 Successful delivery and survival of a premature 29 week old baby with gross fetal hydrops secondary to congenital complete heart block

A 32 year old woman presented at 29 weeks gestation with reduced fetal movements and abdominal pain to her local hospital. An ultrasound scan revealed gross fetal hydrops secondary to...