Sherif A. Abdel-Fattah

Quantification of cell free fetal DNA in maternal plasma in normal pregnancies and in pregnancies with placental dysfunction.

OBJECTIVE To assess the normal levels of free fetal DNA in maternal plasma through pregnancy compared with those in pregnancies complicated with placental dysfunction manifested by preeclampsia and/or fetal growth restriction. STUDY DESIGN Maternal blood samples from 138 singleton male pregnancies were divided into 3 groups; normal pregnancies (77), preeclampsia (49), and fetal growth restriction (12). Royston and Wrights methods were used to calculate gestational age-related reference limits of free fetal DNA in the 3 groups. The DYS14 gene of the Y chromosome was quantified and compared in maternal plasma by using real-time quantitative polymerase chain reaction. RESULTS Free fetal DNA in normal pregnancies increased with gestational age. Results were significantly higher in preeclampsia and fetal growth restriction groups than in normal pregnancy and were higher in severe preeclampsia than in milder disease. CONCLUSION Free fetal DNA is a potential marker for placental dysfunction in pregnancy. Large prospective studies are now needed to investigate its role in the prediction of pregnancy complications and severity and or timing of delivery.

Management and outcome of pregnancies with parvovirus B19 infection over seven years in a tertiary fetal medicine unit

Objectives: To determine rates of fetal anaemia and pregnancy outcome in susceptible pregnant women infected with human parvovirus B19 infection in a tertiary fetal medicine department over a 7-year period. Additional features enabling identification of fetuses that progress to severe anaemia were also investigated. Methods: Forty-seven susceptible, pregnant women with confirmed parvovirus infection referred to a regional fetal medicine unit, over a 7-year period (1999–2006), were identified. Where possible maternal serum AFP measurements were obtained from second-trimester serum screening and the presence or absence of echogenic bowel noted. Results: Of the 47 cases, one was excluded. Of the remaining 46 cases, 34 (74%) showed no signs of fetal anaemia and delivered at term. The remaining 12 (26%) showed signs of fetal anaemia. Eight of the 12 developed hydrops and underwent fetal blood sampling and transfusion (median pretransfusion Hb 3.6 g/dl). Seven of the 8 transfused fetuses were thrombocytopenic with a platelet count <150 × 109/l, with 2 fetuses having platelet counts <50 × 109/l. The median gestation age at transfusion was 22 weeks (range 18–27 weeks). The median number of weeks between seroconversion and transfusion was 6 (range 3–12). The signs of anaemia resolved after one transfusion in 5 of the 8 transfused fetuses and they subsequently delivered at term. There were 2 fetal deaths during or shortly after transfusion and one neonatal death following delivery at 28 weeks gestation due to severe pre-eclampsia, 5 days after successful transfusion. Conclusions: Following parvovirus seroconversion, the incidence of significant fetal anaemia requiring transfusion was 17%. Seroconversion after 21 weeks did not result in severe fetal anaemia. Significant anaemia requiring intervention did not occur 12 weeks after maternal seroconversion. We did not demonstrate a correlation with either maternal serum AFP or the presence of fetal echogenic bowel and the development of severe fetal anaemia. Because of the association between fetal anaemia and severe thrombocytopenia, it may be prudent to have compatible platelets available at the time of fetal blood sampling.

Comparison of different reference values of fetal blood flow velocity in the middle cerebral artery for predicting fetal anemia

To compare different normal reference ranges of fetal blood flow velocity in the middle cerebral artery for predicting fetal anemia.

Optimal Interval between Middle Cerebral Artery Velocity Measurements when Monitoring Pregnancies Complicated by Red Cell Alloimmunization

Objective: To evaluate the optimal interval between middle cerebral artery (MCA) Doppler measurements when monitoring pregnancies complicated by red cell alloimmunization. Methods: Thirty-nine fetal blood samplings (FBS) performed on 24 pregnant women with red blood cell alloimmunization followed up using both MCA peak systolic velocity and time-averaged mean velocity measurements on weekly basis. Results: In total, 65.5 and 37.5% of women with moderate or severe fetal anemia had abnormal MCA Doppler values 1 and 2 weeks, respectively, before FBS was performed. Conclusions: A weekly assessment of women at risk for fetal anemia is optimal in most of the cases even though 35.5% of cases of moderate or severe fetal anemia are expected to have normal Doppler measurements the week before the decision of doing an FBS is made.

Fetal karyotyping by chorionic villus sampling after the first trimester

Objective To evaluate chorionic villus sampling (CVS) as a technique for karyotyping after the first trimester by examining the incidence of result failure, confined placental mosaicism, and false positive or negative results at different gestational ages.

Neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and newborn and managed with intrauterine transfusion: a service evaluation

BACKGROUND This study, conducted in the tertiary Foetal Medicine Unit at St Michaels Hospital, Bristol, was designed to obtain information regarding neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and newborn and managed by intrauterine transfusion, and to determine whether a change in intrauterine transfusion protocol in 2004 had improved safety. The new protocol included attendance of two Foetal Medicine Unit consultants, foetal sedation and use of the intrahepatic vein as an alternative route to placental cord insertion if deemed safer. MATERIALS AND METHODS Data for pregnancies affected by haemolytic disease of the foetus and newborn as a result of haemolytic red cell alloimmunisation and managed with intrauterine transfusion at St Michaels Hospital between 1999 and 2009 were retrospectively collected using local databases, and medical note review. RESULTS Overall, 256 relevant intrauterine transfusions were performed. The median number of intrauterine transfusions per pregnancy was two. Ninety-three per cent of the live deliveries had 5-minute APGAR scores ≥9 and 98% were admitted to a Neonatal Intensive Care Unit/Special Care Baby Unit, requiring phototherapy (96%), top-up transfusions (44%: 23.2% immediate, 13.4% late, 7.3% both), and exchange transfusion (37%). An association was found between increased intrauterine transfusion number and reduced phototherapy duration and hospital admission: each additional intrauterine transfusion reduced the duration of phototherapy by 16% (95% CI: 0.72-0.98), and Neonatal Intensive Care Unit/Special Care Baby Unit admission by 44% (95% CI: 0.48-0.66). Following the change in intrauterine transfusion protocol, there was a significant reduction in the number of emergency Caesarean sections occurring directly after an intrauterine transfusion (n =5 vs 0; P =0.02). The foetal loss rate within 48 hours of an intrauterine transfusion was 1.9% per pregnancy, or 0.8% per intrauterine transfusion: no losses occurred under the new protocol (n =3 vs 0; P = NS). DISCUSSION Although the majority of neonates required admission to a Neonatal Intensive Care Unit/Special Care Baby Unit and phototherapy, the medium-term outcomes were positive. Importantly, the safety of the intrauterine transfusion procedure has improved significantly since the change in protocol.

Amnioreduction : How much to drain?

Objectives: To assess the relationship between the volume of amniotic fluid removed and the change in amniotic fluid index (AFI) and calculate an equation describing this association. Materials and Methods: A retrospective analysis of 19 amnioreduction procedures performed in our unit. Multiple regression analysis was used to assess the effect of gestational age and pre-procedure AFI on the change in AFI (ΔAFI) after adjusting for the volume removed. Results: As expected, a significant linear relationship was found between the change in AFI and the volume removed (r = 0.82, n = 19, p < 0.0001). ΔAFI was not dependent on the gestational age or the pre-procedure AFI. The equation describing the association between the volume removed and ΔAFI was: volume = (ΔAFI – 2.26)/0.008, which is close to 1 cm ΔAFI for every 100 ml removed. Discussion: Using the described equation, it is possible to predict the required volume to be removed in order to achieve a particular ΔAFI, which may reduce the need to interrupt the procedure to measure the AFI. However, the limitation of AFI as a semiquantitative assessment of the liquor volume, together with its inter- and intra-observer variations mean this equation should be used only as a guide.

Non‐invasive prenatal diagnosis

Obtaining fetal material for molecular analysis without the need for invasive procedures has been a goal of fetal medicine for many years. This is becoming a reality now that circulating cell‐free fetal nucleic acids can be detected in maternal plasma. Tests are already being used in clinical practice for the management of X‐linked conditions through the determination of fetal sex and for red cell alloimmunisation by prediction of fetal rhesus D status. The sensitivity of this technique produces highly accurate results, thereby reducing the number of invasive procedures needed. This approach has also been used in the diagnosis of genetic disorders and in obstetric complications where the level of free fetal DNA may be a marker for placental abnormalities.

Live Birth after rupture of a non-communicating horn of a bicornuate uterus

A 33-year-old woman presented with abdominal pain at 30 weeks of gestation. A previous pregnancy had resulted in a ventouse delivery of a live boy. Her second pregnancy had been complicated by first trimester vaginal bleeding. First and second trimester ultrasound confirmed a bicornuate uterus with a live fetus in the left-sided moiety. She booked with her community midwife for home delivery. At 30 weeks of gestation she presented with sudden onset of cramping abdominal pain several hours after a grape seed oil massage. She had no associated vaginal bleeding and fetal movements were normal. Examination showed an appropriate symphysio-fundal height, breech presentation and mild tenderness over the uterus. Her observations were normal and fetal cardiotocograph (CTG) was satisfactory. Three hours later her pain and uterine tenderness increased and a fetal bradycardia was followed by fetal tachycardia. She was taken to theatre for caesarean section under general anaesthetic with the likely diagnosis of concealed placental abruption. Intra-abdominal haemorrhage was found. A lower uterine segment incision was made but the fetus was not found within this cavity. A classical incision was then performed over the left side of the uterus and a female infant delivered with an Apgar score of three at 1 minute and eight at 5 minutes. She was intubated and resuscitated by the neonatologists and transferred to the neonatal intensive care unit. Following delivery the uterus was externalised for closer inspection. The uterus had ruptured at the left side of the fundus. There was a thick septum dividing the uterus into two halves with no connection between the left side and right side and no connection between the left side of the uterus and the cervix. Furthermore, there was evidence of placental implantation in the left side of the uterus (Fig. 1). The combined effect of a lower segment and classical incision, in addition to a ruptured fundus, resulted in an atonic uterus. Despite suturing, pressure, syntocinon and the prostaglandin analogue carboprost (Hemabate), haemostasis was not achieved so the decision was made to proceed to caesarean hysterectomy. Following a 10-unit blood transfusion and high dependency care she made a full recovery and was discharged on day 7. The baby required 24 hours of intubation and surfactant. She received antibiotics for three days and remained on the neonatal unit to establish feeding. She was discharged on day 40. At their postnatal appointment nine weeks later both mother and baby were doing well.

The Effect of Fetal Hydrops on the Rate of Fall of Hemoglobin after Fetal Intravascular Transfusion for Red Cell Alloimmunization

Objective: We aimed to assess whether there is a difference between hydropic and nonhydropic fetuses in the rate of fall of hemoglobin (Hb) following intravascular transfusions. Methods: Eighty-three intravascular transfusions in 34 fetuses were analyzed. The pretransfusion and posttransfusion Hb values, the gestational age, the volume of blood transfused, the number of days between transfusions and the rate of fall of Hb per day following a transfusion were assessed. Hb levels were expressed as multiples of standard deviation from the normal mean for gestational age. Results: Eleven fetuses were hydropic at presentation and 23 were not. Twenty-three transfusions were undertaken in the 11 fetuses while they were hydropic and 60 transfusions were performed in nonhydropic fetuses. Comparisons of transfusion variables between the two groups were performed both for the first transfusion only and also for the total number of transfusions. The rate of Hb fall per day following a transfusion was similar in the two groups on both comparisons. The posttransfusion Hb level tended to be lower and the intervals between transfusions were a little shorter in the hydropic group, but these differences were not statistically significant. Conclusion: The posttransfusion Hb tended to be lower in the hydropic fetuses, but the fall in Hb was not faster in these cases. Therefore, with a similar rate of daily Hb decline in both groups, the hydropic fetuses are expected to become anemic again sooner than the nonhydropic fetuses only because of the lower posttransfusion Hb. The timing of the next transfusion should therefore be based on the posttransfusion Hb and the normal predicted drop per day irrespective of the presence or absence of hydrops.