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British Journal of and July 1997, Vol. 104, pp. 803-810 The obstetric experience of carriers of haemophilia

*R.A. Kadir Clinical Research Fellow, *D. L. Economides Consultant/Senior Lecturer, *J.Braithwaite Clinical Research Fellow, tE. Goldman Associate Specialist (Haematology), tC. A. Lee Consultant (Haematology)/Director *Departmentof Obstetrics and Gynaecology,and THaemophilia Centre, Department of Haematology, The and School of

Objective To review the obstetric problems, outcome and management of carriers of haemophilia. Design Retrospective review of haemophilia and maternity unit records. Setting Haemophilia Comprehensive Care Centre. Participants Thirty-two carriers of haemophilia (24 , eight ) who had their obstetric care at the Royal Free Hospital over a 10-year period (1985-1995). Main outcome measures Uptake and results of prenatal diagnosis, changes in factor levels during pregnancy, effect of knowledge of fetal gender on obstetric management and neonatal outcome, and maternal haemorrhagic complications. Results There were 82 and 32 resulted in miscarriage or social abortion. The option of prenatal diagnosis was taken up in only 35% (17/48) of pregnancies. There were five affected male fetuses diagnosed prenatally but only three women opted for termination of the pregnancy. Knowledge of fetal gender was unavailable to the attending obstetrician in 46% (21/46) of pregnancies. A fetal scalp electrode was applied in eight, fetal sampling was performed in four, and ventouse delivery was conducted in one of these pregnancies. No adverse effects were reported from the first two procedures, but the ventouse delivery was associated with a huge cephalhaematoma requiring . On the other hand, in five cases fetal blood sampling was withheld because fetal gender was unknown. Four of the eight caesarean sections performed might have been avoided if the gender had been known. The incidence of primary and secondary postpartum haemorrhage was high, 22% (including two cases with massive haemorrhage) and 11%, respectively. Conclusion Carriers of haemophilia A and B require special obstetric care with close liaison with the haemophilia centre, and management guidelines should be available and observed. Knowledge of fetal gender is very valuable for management in labour and should be determined antenatally even if the mother declines prenatal diagnosis.

INTRODUCTION Since female carriers have a second normal from one parent the clotting factor level is expected to Haemophilia A and are uncommon conditions with a B be around 50% of normal, which is generally sufficient the general population of 1 to per prevalence in 2 for normal haemostasis. However, a wide range of func- 10,000 and 1 to 2 per 100,000, respectively'. The tional activities has been reported and in 10% to 20% of genetic defect on the results in an absent carriers extreme LyonisationZ results in significantly or low level of plasma factor VIII in haemophilia A, and low levels of factor VIII and IX (less than 40%) and an factor IX in haemophilia B. The advent and appropriate increase of haemorrhagic problems specially in those use of clotting factor concentrates have dramatically with very low levels (5% to In addition, 50% of improved the and quality of life of male fetuses of carriers of haemophilia are likely to be patients with clotting factor deficiencies. This increased affected. If mothers reject prenatal diagnosis their longevity and the obvious improvement in the general male infants may be unknowingly at risk of traumatic and reproductive fitness among men with haemophilia haemorrhage. over the last 40 years has resulted in an increase in the There are few studies addressing the haemorrhagic birth of daughters who are obligate carriers. problems for carriers of haemophilia and their fetuses in Correspondence: Mr D. L. Economides, Department of Obstetrics pregnancy and delivery. The Royal Free Hospital has a and Gynaecology, The Royal Free Hospital, Pond Street, Hampstead, large, comprehensive care centre for haemophilia and London NW3 2QG, UK. many carrier women have their pregnancy care at this

0 RCOG 1997 British Journal of Obstetrics and Gynaecology 803 804 R. A. KADIR ET AL. 182 pregnancies 48 offered prenatal diagnosis 2 carrier states identified

17 had prenatal diagnosis 31 declined prenatal diagnosis

10 chorionic villous sampling 7 fetal sexing by 2nd trimester u/s

I I r I

1 spontaneous abortion 2 alive and well

Fig. 1. Uptake and results of prenatal diagnosis in camers of haemophilia. TOP = termination of pregnancy; UJs = ultrasound. hospital. The aim of this study was to assess pregnancy haemorrhage (blood loss in excess of 500 mL during the outcome with particular regard to problems in 24 hours after the birth of the infant) and secondary both mother and fetus. postpartum haemorrhage (bleeding in excess of normal lochial loss after first 24 hours of delivery to 6 weeks); METHODS 4. mode of delivery including indications for instru- mental deliveries and caesarean sections; 5. Neonatal Thirty-two carriers of haemophilia (24 haemophilia A, outcome with special emphasis on haemorrhagic com- eight haemophilia B) registered at the Royal Free plications and impact of invasive monitoring techniques Hospital Haemophilia Centre who had obstetric care at and mode of delivery on these complications. this hospital over a 10-year period (1985-1995) were Student’s t test was performed to test for significant investigated. Twenty four were known as obligate carri- changes in clotting factor levels during pregnancy. ers, carrier status was suspected in six of the women during the antenatal period and was confirmed in the RESULTS postnatal period, and diagnosis of carrier status was Prenatal diagnosis and antenatal care made in the remaining two after birth of an affected male. Of the 82 pregnancies, 32 resulted in miscarriage or These women had a total of 82 pregnancies and both termination for social reasons (Fig. 1). Of the remaining the Haemophilia Centre and maternity casenotes were 50, prenatal diagnosis was offered to the women in 48 reviewed with particular emphasis on the obstetric pregnancies (in two pregnancies the carrier status was experiences and status during pregnancy discovered postnatally). The women opted for prenatal and the puerperium. Information recorded included: diagnosis in only 17/48 (35%) pregnancies. The meth- 1. baseline (nonpregnant) clotting factor levels and any ods used and results are shown (Fig. 1). Termination of changes in pregnancy; 2. uptake and results of prenatal pregnancy was performed in 3 cases with an affected diagnosis; 3. occurrence of bleeding during pregnancy fetus and there was one miscarriage of an unaffected and postpartum period including primary postpartum male fetus following cordocentesis.

0 RCOG 1997 Br J Obstet Gynaecol 104, 803-810 THE OBSTETRIC EXPERIENCE OF CARRIERS OF HAEMOPHILIA 805

was not performed in five of them because of this. In two of these five cases, emergency caesarean section was performed (Table 1; case no. 7,9), another two had forceps delivery (Table 1; case no. 1,3) and in the fifth case cardiotocogram (CTG)improved while the woman was being prepared for caesarean section and she had a vaginal delivery. However, among the four cases where the procedure was performed, there was one affected male fetus who suffered no adverse effect. The mode of delivery was a normal vaginal delivery I in 32 pregnancies (intact perineum in 14, vaginal Pre-pregnancy Factor level tears in nine, episiotomy in nine). Details of the forceps, factor level 28-34 weeks ventouse and caesarean section deliveries are shown in Table 1. A severe cephalhaematoma developed subse- Fig. 2. Changes in factor VIIl (n = 6) and IX (n = 3) levels during pregnancy. quent to ventouse delivery in one fetus later found to be an affected male, infant of a known carrier mother. Of the eight caesarean section deliveries, knowledge of Among the 46 ongoing pregnancies, the gender of gender might have influenced management in four the fetus was determined in 13 from prenatal diagnosis, cases (Table 1; case no. 7,8,9,12). and was requested by the obstetrician in a further 14 None of the caesarean sections was performed under pregnancies. The fetal genital area was visualised ante- regional anaesthesia. However, epidural analgesia was natally by ultrasound at 18 to 20 weeks of gestation in the method of pain relief during labour in six of the total 12 of these 14 cases. In these 12 there was correct group. Factor levels were > 50% in five of these but was gender assignment. There was failure to visualise the unknown in the sixth patient as her haemophilia carrier genital area in two cases and no later attempts at gender status was diagnosed postnatally. There were no reported assignment were made. In five others pregnancies, complications from the procedure in any of the six cases. the mothers specifically did not want fetal sexing. In 14 pregnancies with known carrier status, no gender Maternal haemorrhagic complications diagnosis was offered. Therefore, in 2 1/46 (46%) preg- nancies, fetal gender was not available to the attending These were all postpartum. There were 10 primary obstetrician during labour. postpartum haemorrhages (Table 2), two of which were The nonpregnant mean factor VIII level in carriers of massive. Two caesarean sections were followed by haemophilia A was 52.5 IU/dL (median 56, range significant postpartum haemorrhage. Although the 18-96) and nonpregnant mean factor IX level in haemo- factor levels were below 50% in six of these cases, pro- philia B was 57 IU/dL (median 48, range 16-80). Factor phylactic treatment was not arranged to cover delivery levels were checked in nine and three pregnancies in the and the postpartum period. (l-deamino- second and/or third trimesters in haemophilia A and B 8-arginine vassopressin [DDAVP]) was administered carriers, respectively (Fig. 2). Most of the carriers prophylactically immediately after delivery in only of haemophilia A showed a significant increase in three women and in another who had a postpartum factor VIII levels (P < O*OOl)but there was no signifi- haemorrhage within 30 minutes of delivery. This cant increase in factor IX in carriers of haemophilia B. resulted in an increase in factor level in these patients (mean factor level was 46 IU/dL before and 84 IU/dL after DDAVP administration, respectively). Intravenous Labour and mode of delivery access in labour was established in 15 women but in The mean gestation at delivery was 39.2 weeks (range only four of them was this because of the haemophilia 34-42). Fetal scalp electrodes were used for fetal moni- carrier status. There were five secondary postpartum toring in labour in eight pregnancies where the fetal haemorrhages and retained products of conception were gender was not known. Two of these fetuses were obtained in only one (Table 2). subsequently found to be affected males. Fortunately there were no adverse affects from the use of fetal scalp Neonatal complications electrodes in these cases. On the other hand fetal scalp electrodes were required for fetal monitoring in Of the 46 infants born 24 were male (eight were three cases but withheld due to lack of knowledge of the confirmed to have haemophilia) and 22 were female. gender. Fetal blood sampling was considered essential The mean birthweight was 3.25 kg (range 2.34-4.26). in nine pregnancies where gender was not known but There were three neonatal problems in affected male

0 RCOG 1997 Br J Obstet Gynaecol 104, 803-810 806 R. A. KADIR ET AL.

Table 1. Operative deliveries in haemophilia carriers. VE = Vacuum extraction; NK = not known; CTG = cardiotocogram; FBS = fetal blood sampling; LSCS = lower segment caesarean section; Hb = haemoglobin.

Case Gestation Fetal sex Mode of Haemophilia no. (weeks) if known* delivery Indication status of fetus Comments

Instrumental vaginal deliveries 1 39 NK Forceps Fetal distress Affected male Outlet forceps, no neonatal problems 2 40 Female Forceps Prolonged 2nd stage Female Fetal sex was known to be female 3 38 NK Forceps Fetal distress Female Low mid cavity forceps 4 41 Male Forceps Prolonged 2nd stage Affected male Forceps was considered less traumatic than LSCS. No neonatal problems 5 38 Female VE Prolonged 2nd stage Female Fetal sex known to be female 6 38 NK VE Prolonged 2nd stage Affected male Huge cephalhaematoma fetal Hb dropped to 5.2 g/dL Caesarean sections 7 39 NK Abnormal CTG Affected male FBS was not performed because fetal sex was NK 8 40 NK Breech + fetal sex NK Unaffected male Unavailability of fetal sex influenced decision regarding mode of delivery 9 39 NK Delay in 2nd stage Female FBS and mid cavity forceps could not be performed +Abnormal CTG because fetal sex was NK 10 39 Male Previous LSCS Unaffected male Previous LSCS for cephalopelvic disproportion 11 39 Male Delay in 2nd stage Affected Male Instrumental delivery was not attempted because the fetus was known to be affected male . There was marked scalp bruising and cephalhaematoma. Postpartum haemorrhage of 1200 mL 12 34 NK Breech + fetal sex NK Female Unavailability of fetal sex influenced decision regarding mode of delivery 13 39 Female Face presentation Female 14 31 NK Failed induction Unaffected Male

*In labour for instrumental vaginal deliveries; before delivery for caesarean sections. infants as a result of haemophilia. One infant suffered a Recent advances in molecular genetic procedures huge cephalhaematoma after a ventouse delivery result- have resulted in accurate DNA-based prenatal diagnosis ing in subsequent anaemia (haemoglobin 5.2 g/dL) and have therefore increased the available options for requiring transfusion but there was no intraventricular camer women. However, there was a low uptake of haemorrhage. A second infant already known to be an prenatal diagnosis (35%) in our study and termination affected male, was delivered by caesarean section after was chosen in only half of the affected pregnancies. a 2 hour second stage and there was marked bruising Similarly, Varekamp et aL4 evaluating the attitudes and a cephalhaematoma but again no intraventricular toward prenatal diagnosis among 549 nonpregnant haemorrhage. A third infant was inadvertently given potential and obligate carriers of haemophilia found that intramuscular vitamin K before the diagnosis of haemo- only 31% of the study group would favour prenatal philia was made and developed extensive deep bruising diagnosis, with the implication of a possible abortion in around the site which settled with conservative manage- early pregnancy, and half of them would choose this ment and did not require blood transfusion. Admission option even at 16 to 20 weeks. Most of the women who to the intensive care unit was required for six infants. In objected to prenatal diagnosis did so because they did two (Table 1; case no. 6, 11) this was directly associated not consider haemophilia to be a sufficiently serious with bleeding complications. Preterm delivery, meco- disorder to justify an abortion. Nowadays, with the nium aspiration and low Apgar scores were reasons for availability of analysis (by linked poly- admission in the other four. morphism or direct identification of the gene causing the disease), chorionic villus sampling has become the main method of prenatal diagnosis and deter- DISCUSSION mination of fetal clotting factors by cordocentesis is The little published information on the obstetric prob- used only in special circumstances (e.g. when the lems of carriers of haemophilia A and B involves only a mother’s DNA analysis is noninformative or adequate small number of women. Our study represents the information about the family cannot be obtained). largest detailed assessment of the obstetric outcome of Therefore, accurate prenatal diagnosis is not only carriers of haemophilia from one centre and illustrates possible but also important in the management of the the problems of pregnancy for both mother and fetus. pregnancy. 0 RCOG 1997 Br J Obstet Gynaecol 104, 803-810 THE OBSTETRIC EXPERIENCE OF CARRIERS OF HAEMOPHILIA 807

Table 2. Postpartum haemorrhage in haemophilia carriers. PPH/DFD = postpartum haemorrhage or days from delivery*; VAD = vaginal delivery; LSCS = lower segment caesarean section; VE = vacuum extraction; FFP = fresh frozen plasma; Fc VIII conc = factor VlIl concentrate; Int = intermittent.

Case Factor level Mode of PPH (mL) / Blood Blood no. (U/dL) [gestation] delively DFD* products transfusion Comments

Primary postpartum haemorrhage 1 30 (prenatal] LSCS 1500 Fc VIII conc 4 units Advice from haemophilia centre to give DDAVP immediately after delivery but ignored 2t 42 [prenatal] VAD 1500 FFP 5 units Factor level checked 24 hours post-delivery, was 67 IU/dL 3 50 [28weeks] LSCS 1200 FFP + 3 units Prolonged second stage of labour, lacerations of the lower segment Fc VIlI conc during the operation 4 18 [prenatal] VAD 1000 Fc VIII conc 2 units Bleeding from extended episiotomy wound 5 52 [28weeks] VAD 900 No No DDAVP given immediately after delivery. Bleeding controlled with intravenous oxytocin. Postnatal factor 71 IU/dL 67 27 [prenatal] VAD 900 FFP No Prolonged uterine atony required IV ergometrine and intravenous oxytocin infusion 7 38 [34weeks] VAD 800 Recombinant No Recombinant Fc VIII given to cover labour. Retained placenta, Fc VIII manually removed under Fc VIII cover. Postpartum factor level 55 IU/dL 8 40 [prenatal] VAD 750 Fc VIII conc No The bleeding was from vaginal lacerations 9t 55 [prenatal] VAD 700 No No 10 60 [prenatal] VE 600 No No Secondary postpartum haemorrhage 11 16 [postnatal] VAD 11 Fc VIIl conc No Dilatation and curettage was performed but revealed no retained products of conception 12 32 [postnatal] VAD II FFP No Required evacuation of retained products 13 76 [prenatal] VAD IS No No Endometritis treated by antibiotics 14 68 [prenatal] LSCS Int No No Controlled with combined oral contraceptive pill 15 47 [prenatal] Forceps Int No No Controlled with combined oral contraceptive pill

*PPH for primary, DFD for secondary postpartum haemorrhage. THaemophilia B.

Most female carriers of haemophilia have factors VIII any apparent injury. In other cases these procedures and IX levels within the normal range, although were clinically indicated but not performed due to the the reported range is wide. In our study group the non- lack of knowledge of fetal gender. The inconsistencies pregnant mean value was 52.5 IU/dL (range 18-86) and in the use of both fetal blood sampling and fetal scalp 57 IU/dL (range 16-80) for factor VIII and IX, respec- electrodes may well be attributed to imprecise instruc- tively. Mean factor VIII levels of 54 IU/dL (range tions within obstetric notes or poor understanding of 22-116) and 96 IU/dL (range 44-136) have been haemophilia by the attending obstetricians. Lack of reported in carriers of haemophilia and normal females, prior knowledge of fetal gender also influenced the respectively5,and factor VIII has been shown to be less method of delivery resulting in unnecessary caesarean than 30 IU/dL in 2% of carriers of haemophilia A6. section (Table 1). In pregnancies where karyotyping Pregnancy induces a rise in factor VIII levels in normal has not been performed fetal gender can be assessed women7and in carriers of haemophilia AS.A significant accurately by ultrasound in the mid-trimester" . Indeed, increase in factor VIII concentration (average 37 IU/dL) with the advances in transvaginal sonography this can was found among our patients who had their factor lev- be determined as early as the first trimestert2. It may els checked during pregnancy (Fig. 2). However, this sometimes be difficult to visualise the fetal genital area rise seems to be variable, unpredictable and inconsis- due to fetal position and in these cases ultrasound exam- tent, and not all patients attain normal factor levels (i.e. ination should be repeated until positive diagnosis of > 50 IU/dL)9. Factor IX levels, in contrast, often do not the gender is made. Although some patients would not rise in pregnancy9Joand this trend was also observed in wish to know, this information should be available to our patients (Fig. 2). the attending obstetrician to help intrapartum care. Affected male fetuses are potentially at risk of scalp Labour and delivery are critical periods for affected haemomhage from fetal scalp electrode application and male haemophiliacs. They are at risk of serious fetal blood sampling but there is a lack of published data scalp haemorrhage, including scalp abrasions, cephal- to support this. In our study these procedures were haematoma, subgaleal haematoma and intracranial performed when fetal gender was unknown in some haemorrhage, from the process of birth, invasive cases, including three affected male fetuses, without monitoring techniques or instrumental deliveries. The 0 RCOG 1997 Br J Obstet Gynaecol 104, 803-8 10 808 R. A. KADIR ET AL incidence of intracranial haemorrhage in haemophilic perineal haematoma in 43 pregnancies of carrier newborn infants has been reported to be 1% to 4%I3*l4. women. The tendency to bleed in carriers of haemo- This is more likely to occur in association with philia has been explained by the low plasma levels of traumatic delivery15. Ljung et all6 reviewed mode factor VIII and IX.This was also observed in our study of delivery and perinatal bleeding in 117 infants with as most of the significant postpartum haemorrhage moderate or severe haemophilia. They concluded that occurred in patients with pre-pregnancy factor levels the risk of serious bleeding in normal vaginal delivery is below 50 IU/dL (Table 2). small and that delivery of all fetuses known to be at risk DDAVP is a synthetic analogue of antidiuretic of haemophilia by caesarean section is not expected hormone. Administration results in an increase in factor to eliminate the risk. However, the use of vacuum VIII and Von Willebrand’s factor via V2 receptors24. extraction was shown in the same study to constitute a There have been no controlled studies of the use of significant risk factor as 10 of 12 infants with subgaleal DDAVP during pregnancy and its safety and efficacy and cephalhaematoma were delivered by this instru- in obstetric practice has not yet been determined. ment. Indeed, in our study the one affected male infant Some haematologists and obstetricians recommend that delivered by ventouse extraction developed a huge DDAVP should be avoided during pregnancy. However, cephalhaematoma extending distally to the neck, neces- there have been several publications in the management sitating blood transfusion and prolonged neonatal of pregnant women with diabetes insipidus using admission. The association of intracranial haemorrhage DDAVP with no harm to the fetus. DDAVP is very with traumatic deliveries was also reported by Kletzel et specific to V2 receptors and has little effect on smooth al. l7 in three of four haemophilic infants with post- muscle Vl receptors and consequently does not cause delivery head bleeding, with use of forceps in two and uterine c~ntraction~~.In the few patients we have vacuum extraction in one. Therefore, fetuses at risk of treated immediately post-delivery the results have been haemophilia should be delivered by the least traumatic very encouraging. DDAVP has no effect on factor IX method. Prolonged labour, and especially prolonged levels and factor IX concentrates would be required to second stage of labour, should be avoided and early cover delivery in carriers of haemophilia B with low recourse to caesarean section should be considered. levels. High-purity factor IX concentrate should be used Although vacuum extraction should not be used, low as, factor IX concentrate containing factors 11, VII forceps delivery may be considered less traumatic than and X is potentially thr~mbogenic~~.~~.Plasma derived caesarean section when the head is deeply engaged concentrates of coagulation factor VIII carry a small in the pelvis and delivery can be achieved as an easy risk of transmitting A and parvovirus B1928. outlet procedure and performed by an experienced The latter is of particular importance in pregnant obstetrician. Mid cavity forceps and forceps involving women as it can cause severe fetal infection and the rotation of the head should not be used. hydrops fetalis. Therefore, recombinant factor VIII Epidural and spinal anaesthesia in the presence of a should be used when administration of this factor is coagulation defect may cause an epidural haematoma if indicated. a blood vessel inside the spinal canal is punctured and Even in our obstetric unit where the help of the may lead to permanent neurological damageLs. local haemophilia centre is easily available and carriers However, it has been suggested that, provided the coag- of haemophilia are more commonly encountered and ulation screen is normal in patients with haemostatic managed by obstetricians there were many management disorder, there is no contraindication to insertion of an inconsistencies. For most carriers of haemophilia prena- epidural catheter19. In our unit regional block is used tal diagnosis is performed at tertiary referral centres unless factor levels are below 50 IU/dL. In case of where the expertise to obtain chorionic villi or fetal caesarean section, spinal block is regarded as a safer blood is available and where prompt evaluation of the option because a smaller needle is used and is less likely fetal haemophilia status can be quickly assessed. to injure a blood vesse120. Consequently, after prenatal diagnosis the remainder of Carriers of haemophilia have a significantly higher the pregnancy may well be managed at a different hos- tendency to , and also have prolonged bleeding pital where expertise in haemophilia is not present and from small wounds and post-operatively21. We have thus management inconsistencies are more likely. This demonstrated an increased incidence of primary and clearly shows the importance of a protocol of manage- secondary postpartum haemorrhage compared with the ment, as well as the active involvement of a local general obstetric population (22% versus 5%, and 11% haemophilia centre, for these patients. As a conse- versus 0*7%,respecti~ely)~~?~~. Assessment by question- quence of our and other investigators’ findings9and the naire of postpartum haemorrhage in carrier women recommendations of the Haemostasis and reported an incidence of 22%21. Greer et aL9 also Task Force29we propose the following guidelines to aid reported five postpartum haemorrhages and a large consistent and appropriate management:

0 RCOG 1997 Br J Obstet Gynaecol 104, 803-810 THE OBSTETRIC EXPERIENCE OF CARRIERS OF HAEMOPHlLlA 809

1. Pre-pregnancy counselling should be offered, to 9. Intramuscular injections must be avoided in discuss prenatal diagnosis and other aspects of affected male infants or when coagulation status is pregnancy management. Women who may require not known. Vitamin K should be given orally, and blood product should be immunised against routine immunisations should be given carehlly hepatitis B. When there is any doubt about a intradermally or subcutaneously. woman’s carrier status, with DNA 10. Parents should be given follow up counselling and probes should be offered. haemophilic babies should be registered with, and 2. There should be a multidisciplinary approach to the reviewed regularly by, a haemophilia centre. prenatal diagnosis involving experts in the fields of fetal medicine, genetic counselling, haemophilia Acknowledgements care and molecular genetics. 3. For couples who do not wish to have prenatal We thank the staff of the obstetric, haemophilia and diagnosis, we strongly recommend sexing by ultra- neonatal units of the Royal Free Hospital for looking sound at 18 weeks of gestation when anomaly scan after these patients and their babies. We would espe- is performed. The importance of this should be cially like to thank Miss S. Tuck who has always shown emphasised to the couple. If they do not wish to a special interest in the management of these patients. know the gender of the baby, this information should be available to the obstetrician in charge and References written in the notes. 1 Forbes CD. Clinical aspects of the haemophilias. In: Ratnoff OD, 4. The pregnancy should be managed in close liaison Forbes CD, editors. Disorders of Hacrnostasis. New York: Grune & Stratton. 1984: 177-239. with a local haemophilia centre. The mother’s 2 Lyon MF. Sex chromatin and gene action in the mammalian x-chro- factor level should be checked at booking and mosome. AniJHuni Genet 1962; 14: 135-148. at 28 and 34 weeks of gestation. This is espe- 3 Lusher JM, McMillan CW. Severe factor VIII and factor IX defi- ciency in females. Am J Med 1978; 65: 637-648. cially important in patients with low pre-pregnancy 4 Varekamp I, Suurmeijer TP, Brocker-Vriends AH et al. Carrier testing levels (< 50 IU/dL) who would need prophylactic and prenatal diagnosis for hemophilia: experiences and attitudes of treatment for any invasive prenatal diagnostic 549 potential and obligate carriers. Am J Mcd Genet 1990; 37: 147-154. procedures, spontaneous abortion, termination of 5 Rizza C R, Rhymes JL, Austen DE, Kernoff PB, Aroni SA. Detection pregnancy and during labour. of carriers of hemophilia: a ‘blind’ study. Er J Haeoratol 1975: 30: 5. During labour maternal coagulation screen and 447456. 6 Rapaport JJ, Patch MJ, Moore FJ. Anti-hemophilic globulin levels in appropriate factor assays should be checked. It may carriers ofhemophiliaA. JClin Invest 1960; 39: 1619-1625. sometimes be difficult to assess factor levels in 7 Rutherford RN, Hougie C, Banks AL, Coburn WA. The effects of sex labour. In this situation, it is acceptable to rely on and pregnancy on blood coagulation factors. Obstet Gynccd 1964; 24: 886-892. the third trimester factor levels to formulate plan of 8 Kasper CK, Hoag MS, Aggeler PM, Stoue S. Blood clotting factors in management. When the factor level is < 50 IU/dL, pregnancy: factor VIII concentrations in normal and AHF-deficient an intravenous line should be established and women. Obstet Gynecoll964; 24: 242-247. 9 Greer IA, Lowe GD, Walker JJ, Forbes CD. Haemorrhagic problems prophylactic treatment given. The risk of post- in obstetrics and gynaecology in patients with congenital coagu- partum haemorrhage could be firther reduced by lopathies. Br JOhsret Gynaccol 1991; 98: 909-918. minimising maternal genital and perineal trauma. 10 Briet E, Reisner HM, Blatt PM. Factor IX levels during pregnancy in a woman with haemophilia B. Haentosfasis 1982; 11: 87-89. 6. The use of invasive fetal monitoring techniques and 11 Plattner G, Renner W, Went J, Beaudette L, Vain G. Fetal sex detenni- instrumental deliveries, especially vacuum extrac- nation by ultrasound scan in the second and third trimesters. Obster tion, should be avoided in affected male fetuses or Gynecol1983; 61: 454458. 12 Bronshtein M, Rottem S, Yoffe N, Blumenfeld Z, Brandes JM. Early when fetal sex or coagulation status if male is determination of fetal sex using transvaginal sonography: technique unknown. and pitfalls. J Clin Ultrasound 1990; 18: 302-306. Providing the coagulation screen is normal in 13 Eyster ME, Gill FM, Blatt PM, Hilgartner MW, Ballard JO, Kinney 7. TR. Central nervous system bleeding in hemophiliacs. Blood 1978; patients with an inherited bleeding disorder, there is 51: 1179-1188. no contraindication to epidural analgesia. In our 14 Yoffe G, Buchanan GR. lntracranial hemorrhage in newborn and department, regional block for labour or caesarean young infants with hemophilia. JPediatr 1988; 113: 333-336. 15 Bray GL, Luhan NL. Hemophilia presenting with intracranial hemor- section is allowed when the factor level is rhage. Am JDis Child 1987; 141: 1215-1217. 2 50 IU/dL. 16 Ljung R, Lindgren AC, Petrini P, Tengbom L. Normal vaginal deliv- 8. A cord blood sample should be collected in a citrated ery is to be recommended for haemophilia carrier gravidae. Ac/u Paediatr 1994; 83: 60941 I. tube and transferred to haemophilia laboratories 17 Kletzel M, Miller CH, Becton DL, Chadduck WM, Elser JM. Post- within two hours. Results of clotting factors should delivery head bleeding in hemophilic neonates. Ant J Dis Child 1989; be conveyed to the parents by the person most 143: 1107-1110. 18 Moir DD, Thorburn JJ. Some obstetric, anaesthetic and medical com- involved in counselling, usually a staff member plications. In: Moir DD, Thorobum J. Ohsfefric Anaesthc.sia and from the Haemophilia Centre. Analgesia. London: Baillitre Tindall, 19x6: 336-366.

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19 Letsky EA. Haemostasis and epidural anaesthesia. Ini J Obstei 25 Mannucci PM. Desmopressin: a nontransfusional form of treatment Anaesth 1991; 1: 51-54. for congenital and acquired bleeding disorders. Blood 1988; 72: 20 Milaskiewicz RM, Holdcroft A, Letsky E. Epidural anaesthesia and 1 449- 1455. von Willebrand’s disease. Anaesthesia 1990; 45: 462464. 26 Magner A, Aronson DL. Toxicity of factor IX concentrates in mice. 21 Mauser Bunschoten ME, van Houwelingen JC, Sjamsoedin Visser EJ, Dev Biol Stand 1979; 44: 185-1 88. van Dijken PJ, Kok AJ, Sixma JJ. Bleeding symptoms in carriers of 27 Lusher JM. Thrombogenicity associated with factor 1X complex con- hemophilia Aand B. Thromb Huemost 1988; 59: 349-352. centrates. Semin Hemafol1991;28 Suppl6: 3-5. 22 Cunningham FG, MacDonald PC, Grant NF. Abnormalities of the 28 Santagostino E, Mannucci PM, Gringeri A, Azzi A, Morfini M. third stage of labor. In: Cunningham FG, MacDonald PC and Grant Eliminating parvovims B19 from blood products [letter]. Lancet NF. Williams Obstetrics. East Norwalk. Applcton and Larige, 1989: 1994; 343: 798. 4 14424. 29 Walker ID, Walker JJ, Colvin BT, Letsky EA, Riven R, Stevens R [on 23 Lee CY, Madrazo B, Drukker BH. Ultrasonic evaluation of postpar- behalf of the Haemostasis and Thrombosis Task Force]. Investigation tum in the management of postpartum bleeding. Obstet and management of haemorrhagic disorders in pregnancy. J Clin Gynecol1981;58: 227-232. Pathol1994; 47: 100-108. 24 Mannucci PM, Canciani MT, Rota L, Donovan BS. Response of fac- tor VIII/ to DDAW in healthy subjects and patients with haemophilia A and von Willebrand’s disease. Br J Received 4 September I996 Haematoll981;47: 283-293. Accepted 31 January 1997

0 RCOG 1997 Br J Obstet Gynaecol 104, 803-810