Bahrain Medical Bulletin Vo.27, No. 4, December 2005

Sickle Cell Disease in Pregnancy 
H. A. Mansouri, FRCS Canada*  N. Anfanan**
Objective: To determine the maternal and neonatal outcome of pregnancies complicated by sickle cell disease.

Method: The maternal characteristics and antenatal course of patients with sickle cell disease were studied. The patients were treated with either repeated blood transfusions or with exchange transfusion and the development of sickle crisis or hemolytic crisis, preterm labor, chest or urinary tract infections and thromboembolic phenomena were noted. The neonatal outcome was reorced.

Results: The antenatal course of the 25 patients recruited was uneventful for 11 (44%) patients while 14 (56%) required repeated admissions for complications. Five (20%) received repeated blood transfusions while 3 (12%) had exchange transfusion. Four neonates (16%) were of low birth weight due to preterm delivery and intra-uterine growth retardation. No perinatal deaths occurred in this study.

Conclusion: Sickle cell disease was associated with increased maternal morbidity but neonatal and maternal mortality was nil which is much better than previously reported.

Bahrain Med Bull 2005; 27(4):
  
Sickle cell disease is the most common hemoglobinopathy in the United States, with 8% African American subjects carrying the sickle hemoglobin gene1.

In the past, pregnancy for patients with sickle cell disease was fraught with complications that increased the rates of maternal and perinatal mortality. More recently maternal mortality had dropped from 4.1% (before 1972) to 1.7% (after 1972)2. Perinatal mortality had also decreased, although still substantial, from 52.7%to 22.7% after 1972 according to the study of Powars et al3.

*   Consultant and Assistant Professor
     King Abdulaziz University Hospital
** Saudi Board for Medical Specialization
     Jeddah, Kingdom of Saudi Arabia

The maternal risks includes increased frequency of pre partum and post-partum sickling crisis, urinary tract infections, pulmonary complications, anemia and preeclampsia and maternal  death4-6.

The fetal complications include premature delivery with its associated risks, intrauterine growth retardation, and fetal distress during labor and a high rate of perinatal mortality. Repeated prophylactic blood transfusions were thought to decrease the incidence of sickling crisis and possibly improve perinatal outcome7.  In this study we sought to determine the maternal and neonatal outcome of pregnancies complicated by sickle cell disease.

METHOD

This study is a retrospective chart review of patients who had sickle cell disease and delivered between January 1994 to November 2000.  For each patient the following information was retrieved: age, parity, gravidity, number of abortions, previous history of still births and/or neonatal deaths, gestational age at delivery, mode of delivery, and ante partum, intra partum, and postpartum complications including pain or hemolytic crisis, preterm labor, thromboembolic phenomena, chest and urinary tract infections.  The patients were followed by both Obstetrician and Hematologist, they were either treated by repeated or exchange transfusion. Blood transfusion was given as a treatment of low hemoglobin, painful or hemolytic crisis and this required repeated admission to the hospital and occasionally led to transfusion-related complications including abnormal antibodies, HCV and HIV infections. The neonatal characteristics for each patient included:  gestational age at delivery, birth weight, Apgar score at 5 minutes, the occurrence of stillbirth and neonatal deaths.

RESULTS

The mean age of patients was 29 years, with a range of 19- 40 years. Most patients were multigravida but the range of gravidity was between 1-12 with previous history of abortion between 0-4 times.  Out of 25 patients, there were no history of stillbirth, early or late neonatal death, but 4 (16%) had history of preterm birth. None of them had history of infertility, skin or chest infection (see Table 1).

Table 1: Maternal Characteristics of Patients with Sickle Cell Disease during Pregnancy
Patient characteristic	Numbers	%	
Age			
      < 20	3	12	
       20-25	4	16	
        26-30	10	40	
        31-35	4	16	
         > 35 	4	16	
 Parity			
          0	6	24	
          2-4	12	48	
          5-8	4	16	
          > 8	3	12	
History of Preterm Labor	4	16	
History of Skin Infection	0	0	
History of Infertility	0	0	

The antenatal course of these patients varied between uneventful pregnancies in 11 (44%) with no admission to the hospital while the others 14 (56%) had been admitted twice or three times during pregnancy because of complications. These include: vasoocclusive crisis in 7 (28%), hemolytic crisis in 2 (8%), and 1 (4%) had thromboembolic phenomena.

The mean hemoglobin at booking was 10.3g/dl with a range of 6.9-12 gm/dI, while in labor the mean hemoglobin was 9.8gm/dl, with a range of 8.4-12.6 gm/dl. Out of 25 pregnant patients with SCD, 5 (20%) of them had blood transfusion between I - 3 times during their pregnancy while 3 (12%) patients had exchange transfusion once in their pregnancy (see Table 2).

Table 2: Maternal Complications Associated Sickle Disease during Pregnancy
Patient complications	Numbers	(%)	
Vaso-occlusive crisis                                    	14	(56)	
Hemolytic crisis                                             	2	(8)	
Thromboembolic phenomena                        	1	(4)	
Pulmonary complications                               	0	0	
High blood pressure                                      	1	(4)	
Premature rupture of membranes                  	1	(4)	
Preterm labor                                                 	1	(4)	
Blood transfusion                                           	8	(32)	
Exchange transfusion                                    	3	(12)	

None of the patients who had received blood transfusion developed immediate complications although one patient (4%) had abnormal antibodies in her serum. Two patients (8%) developed late sequel of transfusion and had hepatitis C virus infection later on.   Eighteen (72%) patients delivered spontaneously vaginally, one (4%) patient had assisted breech delivery, while six (24%) delivered by caesarean section because of pure obstetric indications. The indications for the cesarean sections included previous cesarean section, footling breech, and fetal distress. None of them had cesarean section because of maternal sickle cell disease (see Table 3).

Table 3: Mode of Delivery of Patients with Sickle Disease during Pregnancy
Mode of delivery	Numbers	(%)	
Spontaneous vaginal delivery	18	(72)	
Cesarean section	6	(24)	
Breech delivery	1	(4)	

The mean birth weight of the neonates was 2.95 Kg with a range of 1.4 to 4 Kg. Out of 25 pregnancies 4 (16 %) had birth weight less than 2500 gm, of those low birth weight, three (12%) of them were preterm. One baby was delivered prematurely at 28 weeks with birth weight of 1265 gm, and Apgar score of 3 at I minute, 8 at 10 minutes. The baby was admitted to special care baby unit (SCABU) and discharged later in good a condition. The second baby was preterm and small for gestational age and was delivered at 31 weeks with birth weight of 1205 gm and Apgar score of 5, 8 at 1 and 5 minutes respectively. The baby was admitted to NICU, and survived the neonatal period but further follow up was not available. The third one was delivered at 36 weeks but was small for gestational age with birth weight of 2035 gm, and Apgar score 5,7,10 at 1, 5, 10 minutes respectively. The baby did well and was discharged home in a good condition.  There were no still births, and early or late neonatal deaths (see Table 4).

Table 4: Fetal Outcome of Pregnancies Associated with Sickle Cell Disease:
Fetal outcome	Numbers 	%	
Stillbirth	0	0	
Neonatal death	0	0	
Preterm delivery	5	(20)	
Intrauterine growth retardation	4	(16)	

DISCUSSION

Obstetric course of mothers with SS disease has shown a gradual and continuous improvement, with a progressive decline in maternal mortality from 11% to nil9.  Most series in the last 30 years have shown negligible maternal mortality, Howard et al, reported two maternal deaths in 81 pregnancies complicated by sickle cell disease, and El shafei et al, reported a maternal mortality rate of 1.4%, while Sun Willburn etal found no maternal deaths in their study population5,9,10. 

There is a general agreement that fetal wastage is increased and birth weight is low in women homozygous with SCD11. The overall perinatal mortality has varied between 10.2% to 12.1% in recent American series, and it was up to 21.8 % in Jamaica4,11.  In Bahrain, the rate was 7.3%5.
In this study there were no neonatal deaths and this could be explained by the small number of patients in the study.

In a review of 270 singleton pregnancies of 175 Jamaican women with sickle cell disease, 31% of the newborns were low birth weight<2500 gms11. Sun et al  reported in his study of 127 deliveries of women with sickle cell disease a relative risk (RR) of 4.1 and 95% CI  (2.4-7.2) as compared to women with AA hemoglobin9.  Fifteen percent of the newborns of women with (SCD) in the study of El Shafie from Bahrain were low birth weight and below the tenth per centile for gestational age5.  The results of this study were similar and 4 (16%) of the neonates were below the tenth percentile.

The cause of increased perinatal mortality and low birth weight is assumed to be due to placental damage and impaired uteroplacental function, placental infarction, calcification and fibrosis, although there have been no convincing studies correlating placental damage with fetal outcome11.

Mikhail et al studied the placenta of 21 women with SCD and 63 low risk control women; he found that the mean fetal birth weight of infants of SCD women was significantly lower than that of the low risk controls, and the mean placental weight was also lower in the SS groups compared with controls. Moderate to severe villous sclerosis and infarction was observed in these placentas but absent in placentas of low risk controls12.

Both bone pain crisis and infections are the commonest complications for which patients were hospitalized; the management of pregnancy with sickle cell disease should be designed to address and if possible prevent these complications13.  Prophylactic blood transfusion to replace sickle cells with normal RBC thereby increasing oxygen carrying capacity and suppressing the synthesis of sickle hemoglobin remain controversial (8), several studies have demonstrated improvement in perinatal outcome and others have shown no significant difference8,10. Howard et al, in a multi center study compared 81 pregnant patients of sickle cell disease with 100 pregnancies of black African women without hemoglobinopathies. Those with sickle cell disease were divided by types of hemoglobinopathies and transfusion regimen, and it was found that there was no significant difference in the number of sickling complications between transfused women with sickle cell disease and those not transfused10.  Also they demonstrated no significant difference in fetal outcome in term of intra-uterine growth retardation, neonatal deaths and still birth of the transfused pregnancies compared with those who were not transfused.  Similar results were obtained in study done by Tuck et al, their patients with hemoglobinopathies were prophylactically transfused starting at first antenatal visit and two units of packed red blood cell regularly transfused at one to two weeks interval.  When these patients where compared with those who were not transfused, there was no significant difference in fetal and maternal outcome6.

In this study, 3 (12%) patients received exchange blood transfusion, one of them because of hemolytic crisis while two because of severe pain crisis. Five (20%) patients received blood transfusions only, four of them were because of pain crisis and the indication for the transfusion of 5th patient was not known.  In spite of blood transfusions two of neonates were growth retarded, which represent 50% of intra uterine growth retardation cases that we had in the study. Hydroxy urea is another modality of treatment, It has been proven to be of benefit in decreasing the frequency of medical contacts; hospital admissions for painful events, episodes of acute chest syndrome and blood transfusion in adults with a severe clinical course of SCA8. The mechanism of action of Hydroxyurea is not known but it causes an increase of fetal hemoglobin concentration11.

Unfortunately, most of the studies of hydroxyurea with SCA were on pediatric population. Reviewing the literature about the effect of hydroxyurea on pregnancy, there was a case report of SCA patient who was treated with hydroxyurea 1 gm/d conceived and discontinued the drug at 9 weeks of gestation. She delivered a healthy male infant with no evidence of congenital malformation. This suggests that the risk of hydroxy urea exposure during pregnancy may have been over estimated14.

CONCLUSION

Sickle cell disease with pregnancy carries a risk to the fetus and the mother, but the overall outcome is favorable, even in patients with high parity (as in this study).   We realize that we have small number of patients to make such general statement, and it would be recommended that other studies should be encouraged in this field.

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