Surveillance of pregnant women with potential exposure to Zika virus following travel.

AIM: To describe the experience of a single fetal medicine unit in evaluating pregnant women with potential exposure to Zika virus (ZIKV) following travel. METHOD: Between February 2016 and June 2017, a multidisciplinary team evaluated pregnant women by developing a local pathway based on Public Health England guidance. All pregnant women were offered serial fetal ultrasound scans (USS). If they presented with a history of clinical symptoms consistent with ZIKV infection during or within two weeks of travel or fetal USS was suggestive of microcephaly, reverse transcriptase polymerase chain reaction (RT PCR) and/or serology was used. RESULTS: 69 women were referred. Eight patients reported symptoms consistent with ZIKV infection (11.6%) and six (8.7%) patients reported mosquito bites. Maternal exposure was mainly during the preconception period and the first trimester in 35 (50.8%) and 19 (27.5%) women, respectively. Prenatally, there was no evidence of microcephaly in any of the 69 referrals. Sixty-two live births and seven miscarriages were reported. One patient had serology confirming ZIKV infection during pregnancy. At birth, 57 babies had normal head circumference (HC) measurements, including the baby born to the Zika positive mother. Two babies had small HC measurements but were not infected and were small for gestational age. CONCLUSIONS: One case of maternal ZIKV infection was detected but without any fetal congenital abnormalities postnatally. The number of potentially infected patients referred to our unit is a demonstration of the concern regarding perinatal ZIKV infection in the pregnant population.

Early fetal growth in progesterone-treated IVF pregnancies.

PURPOSE: The aim of this study was to compare fetal growth in the first and second trimesters of pregnancy and final birth weights between two groups of women: (a) spontaneous conceptions with reliable menstrual dates and (b) IVF pregnancies on progesterone supplementation during the first trimester. METHODS: We included in the study 73 singleton IVF pregnancies and 138 singleton spontaneous pregnancies. Exclusion criteria were: medications or presence of medical conditions affecting fetal growth. Fetal crown-rump length (CRL) at 10 + 1 to 13 + 6 weeks of gestation, and head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) at 18-24 weeks, were measured prospectively. The birth weights of the babies born were collected and compared. Independent sample t test was applied for comparing quantitative variables with normal distribution, and Wilcoxon-Mann-Whitney test was used for comparison of quantitative variables without normal distribution. RESULTS: IVF fetuses on progesterone supplementation had larger CRL measurements when compared to their counterparts from spontaneous pregnancies (p value = 0.045). Similarly, in the second trimester, the BPD was significantly larger but HC, AC and FL, although larger, did not reach statistical significance. The birthweights of babies between the two groups showed no statistically significant difference, although some IVF babies were born prematurely. CONCLUSIONS: Enhanced fetal growth during the first trimester has been observed with progesterone supplementation in IVF pregnancies. Aspects of enhanced fetal growth were observed in the second trimester but not at birth. The effect of progesterone supplementation on fetal growth needs further investigation.

Spontaneous live unilateral twin ectopic pregnancy - A case presentation.

The incidence of ectopic pregnancy has increased in recent years and now is around one in 100 pregnancies. However, the incidence of live twin ectopic pregnancy in a spontaneous conception is still quite rare. A 34-year-old gravida 3, para 0 presented in the Early Pregnancy Unit with a positive pregnancy test, lower abdominal pain and vaginal spotting. Her quantitative serum Beta hCG was high, and the transvaginal scan revealed an empty uterine cavity with a twin ectopic pregnancy in the left adnexa with cardiac activity in both embryos. The patient was taken for laparoscopic surgery and a left ampullary twin pregnancy was confirmed. She underwent a left salpingectomy and is well on a one-year follow-up. This case report discusses the incidence, diagnoses and treatment of ectopic pregnancies in general.

Menstrual problems in university students: an electronic mail survey.

OBJECTIVE: To establish the prevalence of menstrual-related problems among university students. MATERIALS AND METHODS: A questionnaire regarding gynecological, bleeding and family history was sent by electronic mail (e-mail) to all female students attending University College London (UCL). RESULTS: A total of 767 students aged 18-39 years replied; 71% had a regular menstrual cycle. One in three (n = 264) had received some treatment for their menstrual periods (such as the combined oral contraceptive pill or simple analgesia). Those with heavy or painful periods were more likely to feel that their menstrual problems had a substantial impact on their academic and social life; however, even among those with light periods, one in every four females felt that their life was considerably affected. CONCLUSION: A considerable prevalence of menstrual-related problems was demonstrated among this young healthy population. Additionally, the use of e-mail could present potential benefits as a research medium for this kind of study.

Outpatient medical management of missed miscarriage using misoprostol.

We wanted to evaluate the efficacy, safety and acceptability of misoprostol for outpatient management of missed miscarriage. This was a prospective observational study conducted in the early pregnancy unit of a university teaching hospital involving women attending the unit with a diagnosis of missed miscarriage. All women with a missed miscarriage of <12 weeks' gestation and opting to have medical management were eligible for inclusion. Women who consented to take part were given 800 microg of misoprostol in the unit and advised to take two further doses of 400 microg of misoprostol, orally, 3 h apart, the following day at home. Outcome measures included success rates, emergency admission rates, blood transfusion rates, pain scores, satisfaction scores, incidence rates of side-effects and number of women who would choose medical management in future. Of the 268 women diagnosed as having a missed miscarriage during the study period, 75 (28.0%) opted to have medical management. Over three-quarters (n = 58, 77.3%, 95% confidence interval (CI) 66.2 - 86.2) of the women achieved successful complete medical evacuation. Overall, five (6.7%; 95% CI 2.2 - 14.8) women presented for emergency admission. The mean visual analogue scale (VAS) score of all women was 6.7 (SD = 2.8) and the mean satisfaction score was 8.6 (SD = 2.1). Two-thirds of women (n = 50, 66.7%) said that they would choose to have medical evacuation in a future miscarriage, while seven (9.3%) were unsure. A total of 70 (93.3%) women said they preferred to have the treatment at home rather than in the hospital. We conclude that medical evacuation of missed miscarriage is efficacious, safe and acceptable in the outpatient setting.

Is primary postpartum haemorrhage a good predictor of inherited bleeding disorders?

A study was conducted to evaluate the value of screening for inherited bleeding disorders in women with primary postpartum haemorrhage (PPH). Over a 2-year period, women identified to have PPH (defined as >500 mL blood loss for spontaneous vaginal delivery, >700 mL for instrumental deliveries and >1000 mL for caesarean sections within 24 h of delivery) were invited to participate in this study testing for a possible underlying bleeding disorder at 3-9 months post-delivery. Women known to have an inherited bleeding disorder were excluded. Of the 5744 deliveries in our unit during the study period, 152 (3%) fulfilled the criteria for primary PPH and 50 women agreed to participate in the study. Of these, 25 (50%) had a spontaneous vaginal delivery, 8 (16%) had an instrumental delivery and 17 (34%) had a caesarean section. Half of the women were multiparous and five (20%) had PPH in their previous pregnancy. Nineteen (38%) and 12 (24%) reported at least one significant personal and family bleeding history, respectively. One (2%) woman was identified to have von Willebrand disease. In conclusion, primary PPH does not appear to be a strong predictor of inherited bleeding disorders. Further studies are required to assess the prevalence of inherited bleeding disorders among these women.

Screening for factor XI deficiency amongst pregnant women of Ashkenazi Jewish origin.

A pilot study was conducted over a 6-month period to evaluate antenatal screening for factor XI (FXI) deficiency amongst Ashkenazi Jewish women booking for their pregnancy in a single obstetric unit. Fifty-four women of Ashkenazi Jewish origin were recruited during their visit for the routine first trimester ultrasound scan. They completed a questionnaire about their personal bleeding symptoms and had blood taken for FXI levels (FXI:C). Seven (13%) women had partial FXI deficiency. Five (9%) were newly diagnosed, and in the remaining two, the diagnosis was known previously. One infant with severe FXI deficiency was identified as a result of maternal testing. This study has shown that FXI deficiency is common amongst women of Ashkenazi Jewish origin and supports its antenatal screening in this population. However, further studies are required to evaluate its cost-effectiveness and the effect on pregnancy outcome.

Identification and management of women with inherited bleeding disorders: a survey of obstetricians and gynaecologists in the United Kingdom.

A mail survey of members and fellows of Royal College of Obstetricians and Gynaecologists was carried out to determine current practices of obstetricians and gynaecologists in the United Kingdom in the management of women with inherited bleeding disorders. In total, 3929 questionnaires were sent, 707 returned and analysis was limited to 545 valid questionnaires. In the past 5 years, 91% have managed women with inherited bleeding disorders. The majority (83%) considered inherited bleeding disorders to be under diagnosed in obstetrics and gynaecology. More than 80% considered the prevalence of von Willebrand's disease (VWD) to be <0.2% in the general population and <1% in women with menorrhagia and no gynaecological pathology, although the reported prevalence is 1% and 5-25% respectively. Twelve percent of the respondents would arrange testing for VWD when reviewing an 18-year-old with menorrhagia and no pelvic pathology, while only 2% would do the same for a 35-year-old with the same presentation. Twenty-one percent thought elective caesarean section is indicated in all fetuses known to be at risk of being affected by haemophilia. Eighty-four percent considered vacuum extraction unsafe in these cases, but 76% would consider the use of low forceps. In conclusion, obstetricians and gynaecologists underestimate inherited bleeding disorders as an underlying cause for menorrhagia. Increased awareness and management guidelines are essential in minimizing haemorrhagic complications and improving quality of care of these women.

The use of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is used commonly by gynaecologists as a contraceptive and to treat menorrhagia. However, its efficacy has not been examined in women with inherited bleeding disorders. DESIGN: A prospective pilot study. SETTING: A teaching hospital in north London with a designated haemophilia centre. POPULATION: Female patients with a known inherited bleeding disorder. METHODS: Sixteen women with subjective and objective menorrhagia caused by inherited bleeding disorders (13 von Willebrand's Disease, two factor XI deficiency and one Hermansky-Pudlak syndrome), who had previously undergone unsuccessful medical treatment were followed up for nine months after LNG-IUS insertion. Bleeding was measured by pictorial chart and haemoglobin concentration. RESULTS: All women reported that their periods were improved, pictorial chart scores were lower and 56% became amenorrhoeic. None reported side effects. CONCLUSION: The LNG-IUS is well tolerated and effective and improves quality of life.

Patient acceptance of transvaginal sonography in the early pregnancy unit setting.

OBJECTIVE: To establish the acceptability of transvaginal scanning in patients attending an early pregnancy unit (EPU) due to problems in early pregnancy such as vaginal bleeding. METHODS: An unselected group of pregnant women who were less than 8 weeks' gestation were invited to complete a questionnaire before the transvaginal scan regarding their views about the pregnancy and about the scan itself. They were asked to complete a second questionnaire after the scan had been performed. Information was collected about the presenting symptoms and the final diagnosis. RESULTS: Of a total of 107 patients, the most common reason for attending the EPU was vaginal bleeding (51.4%). The primary concern for the majority of these women was their pregnancy, rather than the scan procedure itself. Their concerns about the scan were not altered by a previous history of miscarriages or by maternal age. After the scan, more than 77% of patients scored < or = 3 out of 10 with regard to discomfort, pain and embarrassment. Only 1.9% experienced marked discomfort, scoring > 8 out of 10. The scores were not altered by the patients' diagnoses. A total of 99% of patients said that they would agree to have a similar procedure in the future. CONCLUSION: This questionnaire-based study confirms that patients attending with problems in early pregnancy find transvaginal sonography acceptable.

Examination of fetal nasal bone and repeatability of measurement in early pregnancy.

OBJECTIVE: To evaluate the examination and measurement of fetal nasal bone at 10-14 weeks of gestation. METHODS: The study included 501 fetuses in 496 consecutive pregnant women attending for the routine first-trimester ultrasound examination. The presence or absence of the fetal nasal bone was determined in the mid-sagittal plane and the length was measured by one of four examiners (measurement A; n = 501). A second measurement was taken by the same examiner (B, n = 300) and a different examiner repeated the measurement (C, n = 200) whenever possible. Measurements were made to the nearest 0.1 mm. The duration of one hundred consecutive examinations was recorded, as was that of another 100 consecutive routine first-trimester examinations without measuring the nasal bone. RESULTS: The median nasal bone length was 1.6 (0.8-2.4) mm, the median gestational age was 12 (10-14) weeks and the median crown-rump length (CRL) was 63 (32-90) mm. The fetal profile was examined in all 501 cases and the fetal nasal bone was present in all but one case (99.8%). No transvaginal scans were needed for the examination of nasal bone only. The average time for the sonographic examination (8.3 min) was not significantly different from the average time for first-trimester scans in which the fetal nasal bone was not measured (8.0 min). The fetal nasal bone length increased from 1.1 mm at a CRL of 35 mm to 2.1 mm at a CRL of 90 mm (nasal bone = 0.016 x CRL + 0.619, P < 0.001, r = 0.655). The repeatability coefficient for intraobserver measurements was 0.080 mm and the coefficient for interobserver measurements was similar (0.083 mm). CONCLUSIONS: The nasal bone can be detected from 10 weeks of gestation onwards. Consistent visualization and repeatable measurement of fetal nasal bone can be performed by an experienced sonographer in the first trimester without extending the length of time required for scanning or introducing the need for transvaginal sonography.

The use of three-dimensional ultrasound for fetal gender determination in the first trimester.

The objective of this study was to examine the accuracy of fetal gender prediction at a routine first trimester scan using three-dimensional (3D) ultrasound. 200 women were recruited for this study and they agreed to have a transvaginal scan for their routine first trimester scan for fetal anatomy and nuchal thickness measurement. 3D volumes were obtained and stored. Two examiners independently reviewed all the volumes and recorded their diagnosis of fetal gender and measured the angle between the genital tubercle and the skin overlying the sacrum. After studying the 3D volumes both examiners recorded a diagnosis of male or female in 150 cases (81.5%). In 34 cases (18.5%) either both (n=21) or one of them (n=13) could not comment on fetal gender by studying the saved volume. From these 150 cases correct prediction of fetal gender by both examiners was achieved in 85.3% of cases. In 6.7% of cases both examiners predicted the wrong gender while for the rest 8% of cases each examiner assigned different gender to the fetus (k=0.84; standard error 0.045). Angle measurements performed from the saved 3D volumes were highly reproducible. Gestational age did not affect the accuracy of gender identification. This study demonstrates that 3D ultrasound can be an effective and fast way of identifying fetal gender in the first trimester. The advantages of 3D ultrasound stem from its ability to virtually reproduce all required views.

DDAVP nasal spray for treatment of menorrhagia in women with inherited bleeding disorders: a randomized placebo-controlled crossover study.

To assess DDAVP (1-deamino-8-d-arginine vasopressin; desmopressin) nasal spray in the management of menorrhagia in patients with inherited bleeding disorders, 39 women (aged 18-50 years) with menorrhagia were recruited and were randomized to start 2 months' therapy with placebo or DDAVP (300 micro g) spray in a double-blind crossover study. Twenty-eight and 24 completed first and second period of treatment, respectively. Menstrual loss was assessed using the pictorial blood assessment chart (PBAC) during each treatment period. The main outcome measure was comparison of PBAC scores following DDAVP and placebo treatments. The safety of DDAVP spray was also assessed by monitoring side-effects. Overall, PBAC scores were significantly lower in the second treatment period than the first (P = 0.01). After adjusting for this differences, mean PBAC scores were slightly lower (mean difference 8; 95% confidence interval of - 15.5 to 31.6) in women receiving DDAVP than when receiving placebo, although this difference was not statistically significant (P = 0.51). In conclusion, although there was an indication that menstrual bleeding was less heavy when women received DDAVP than when receiving placebo, the small sample size meant that this difference was not significant.

The influence of maternal hematocrit on placental development from the first to the second trimesters of pregnancy.

OBJECTIVES: To study the influence of maternal hematocrit (Ht) and hemoglobin (Hb) levels on placental size and growth in the first and mid-second trimesters of pregnancy. SUBJECTS/METHODS: This was a prospective study performed at the fetal medicine unit of a university hospital. One hundred and eighty-one women with a singleton pregnancy were recruited at 11-14 weeks' gestation. For each case three scans of the placenta were performed, the first at recruitment and the following two at 3-week intervals. The volume of the placenta was measured at each visit using a three-dimensional ultrasound scanner. The maternal Hb and Ht were measured within 2 weeks of the first scan. RESULTS: The placental growth during the second trimester was inversely related to the Ht levels (r = -0.29, P = 0.001). It was also related to the Hb level (r = -0.20, P = 0.021). An increase of 0.1 units of Ht was associated with 38% less growth of the placenta (95% confidence interval: 18-54% less growth). DISCUSSION: This study demonstrates the effects of maternal environment on placental growth. Our data suggest that the levels of Ht appear to affect the placental growth during the second trimester. Further studies on the factors that regulate placental growth are needed to elucidate the pathophysiology of these interactions and their effect on pregnancy outcome.

Assessment of fetal anatomy in the first trimester using two- and three-dimensional ultrasound.

The objective of this study was to perform a complete anatomical survey of the fetus at 12-13 weeks gestation using stored volumes acquired by a three-dimensional (3D) scanner. 159 consecutive women at 12-13 weeks gestation who had a routine early pregnancy scan in our unit were recruited. A complete survey of the fetal anatomy was attempted by two-dimensional (2D) transabdominal and, if needed, transvaginal ultrasound. Then, using a 3D transvaginal probe, two volumes of the whole fetus were acquired. A complete anatomical survey (excluding anatomy of the heart) was attempted using the stored data. A complete anatomical survey was achieved in 93.7% (149) of cases with 2D ultrasound compared to 80.5% (128) of cases with 3D volume acquisition (p<0.001). The nuchal translucency was measured with 2D scanning in 98.7% of cases and in 91.8% of cases using 3D volumes. The mean time to perform a 2D scan was 12.2 min standard deviation (SD 3.4 min) while the mean time to obtain and examine the stored volumes was 8.4 min (SD 1.45 min, p<0.001). Real-time 2D ultrasound is still the best way to examine fetal anatomy in the first trimester. However, 3D ultrasound can be a useful addition to clinical practice, providing views not easily obtained by conventional 2D ultrasound. It can potentially minimize actual scanning time and provides an excellent way to store scanned data.

Biochemical screening for Down syndrome in pregnancies following renal transplantation.

OBJECTIVE: To assess the performance of the double marker test [free beta-human chorionic gonadotrophin (beta-hCG) and alpha-fetoprotein (AFP)] as a screening test for Down syndrome in pregnant patients who had a prior renal transplant. DESIGN: A retrospective study. SETTING: The Fetal Medicine Unit, Royal Free Hospital, London, UK. METHODS: Detailed records of 14 post-renal transplant pregnancies were obtained from the Renal Unit of our hospital where the patients were followed up. The serum concentrations of urea, creatinine, free beta-hCG and AFP at the time of the double marker test were recorded, with a cut-off point of 1:250 for the double marker test. A control group of 14 normal pregnancies matched for age, parity and gestational age was used. The Mann-Whitney U-test and t-tests of unequal variance were applied to compare parameters of the study and the control groups. RESULTS: Two patients in each group were high risk for Down syndrome and amniocentesis revealed normal karyotype. No babies with Down syndrome were delivered in either group. Regression analysis showed significant correlation between free beta-hCG and urea concentrations (p<0.001) and free beta-hCG and creatinine concentrations (p<0.001), but not for AFP. CONCLUSIONS: The present study demonstrates that residual renal function alterations persisting after renal transplantation can affect the levels of free beta-hCG and AFP, thus resulting in false-positive screening for Down syndrome. First trimester nuchal translucency (NT) measurement in combination with second trimester ultrasonographic markers can be used in these patients, or alternatively the free beta-hCG levels should be corrected according to the serum creatinine levels.

The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's syndrome.

OBJECTIVE: To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. DESIGN: Retrospective five-year review. SETTING: Maternity unit of a university hospital. POPULATION: An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were > or = 37 years old. A subgroup (n = 4,864) also had second trimester biochemical testing by alpha-fetoprotein and free beta-human chorionic gonadotrophin. MAIN OUTCOME MEASURES: Prenatal and postnatal diagnosis of trisomy 21. Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. CONCLUSION: First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester.

Retrospective prenatal diagnosis of scimitar syndrome aided by three-dimensional power Doppler imaging.

Scimitar syndrome is a rare malformation of the arterial supply and venous drainage of the lung. We report the case of a fetus that presented with cardiac asymmetry and malposition of the fetal heart. Postnatally, scimitar syndrome was confirmed at cardiac catheterization. Retrospective reconstruction of three-dimensional power Doppler volumes, obtained during fetal life, allowed direct visualization of the abnormal aortopulmonary collateral vessel. This had not been seen on conventional scans. This case demonstrates many of the strengths of three-dimensional sonographic techniques for the delineation of complex vascular anatomy. It confirms that a prospective diagnosis of scimitar syndrome should be possible during fetal life.