Adverse Pregnancy Outcomes in Sickle Cell Trait: a Prospective Cohort Study Evaluating Clinical and Haematological Parameters in Postpartum Mothers and Newborns

Ali E.H.1, Alkindi S.2, Mohamed A.O.3, Awadalla k.E.4, Abdlgadir O.5, Adam G.6, Magdi M.7, Ibrahim A.K.5 and Ghebremeskel K.1.

1 Lipidomics and Nutrition Research Centre, School of Human Sciences, London Metropolitan University, UK.
2 Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.
3 Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan.
4 Shikan College, El Obeid  Sudan.
5 Sudan Sickle Cell Anaemia Centre, El Obeid - SUDAN.
6 Faculty of Education, Al Azhri University, Sudan.
7 Directorate of Planning, Ministry of Health Oman, Muscat, Sultanate of Oman.

Correspondence to: Professor Salam Alkindi, Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University, P. O. Box 35, Muscat 123, Oman. Phone: +96824141182; Fax: +96824144887. e-mail: sskindi@yahoo.com  ORCID ID: 0000-0001-6863-5748

Published: January 1, 2023
Received: May 15, 2022
Accepted: December 10, 2022
Mediterr J Hematol Infect Dis 2023, 15(1): e2023002 DOI 10.4084/MJHID.2023.002

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective: Sickle cell trait (SCT) is a congenital condition caused by the inheritance of a single allele of the abnormal haemoglobin beta gene, HbS. Carriers of SCT are generally asymptomatic, and they do not manifest the clinical and haematological abnormalities of sickle cell anaemia (SCA). However, there is evidence that they display some symptoms in stressful situations. Pregnancy is a stressful physiological event, and it is not clear if SCT adversely affects pregnancy outcomes, particularly in those from developing countries where people regularly suffer from nutritional insufficiency.
Objective. This study aims to investigate pregnancy outcomes in Sudanese women with SCT.
Subjects and methods. Pregnant women with (HbAS, n=34) and without (HbAA, n=60) SCT were recruited during their first trimester at El Obeid Hospital, Kordofan, Western Sudan. Following appropriate ethical approval and informed consent from the participants, detailed anthropometric, clinical, haematological, obstetric, and birth outcome data were registered. In addition, blood samples were collected at enrolment and at delivery.
Results. At enrolment in the first trimester, the SCT group did not manifest SCA symptoms, and there was no difference in the haematological parameters between the SCT and control groups. However, at delivery, the women with SCT, compared with the control group, had lower levels of hemoglobin (Hb, p=0.000), packed cell volume (PCV, p=0.000), mean corpuscular haemoglobin (MCH, p=0.002) and neutrophil counts (p=0.045) and higher mean corpuscular volume (MCV, p=0.000) and platelet counts (p=0.000). Similarly, at delivery, the babies of SCT women had lower birth weight (p=0.000), lower Hb (p=0.045), PCV (p=0.000), MCH (p=0.000), and higher neutrophil (p=0.004) and platelet counts (p=0.000) than the babies of the healthy control group. Additionally, there were more miscarriages, stillbirths, and admissions to the Special Care Baby Unit (SCBU) in the SCT group.
Conclusions. The study revealed that SCT is associated with adverse pregnancy outcomes, including maternal and neonatal anaemia, low birth weight, and increased risk of stillbirth, miscarriage, and admission to SCBU. Therefore, pregnant women with SCT should be given appropriate pre-conceptual advice and multidisciplinary antenatal and postnatal care.



Introduction

Sickle cell anemia (SCA) is a group of genetic blood disorders characterised by a mutation involving haemoglobin's beta chain. People who inherit one sickle cell gene and one normal gene have sickle cell trait (SCT), whereas those who inherit two abnormal genes have SCA.[1]
Archibald[2] was the first person to report the presence of the HbS gene in Sudan. Subsequently, several studies revealed that the country has a high prevalence of SCA, with an HbS allele frequency ranging between 0.8% in the North and over 30% in the Western part of the country.[3-5] The high HbS allele frequency is due to consanguineous marriages, an influx of tribes affected by the disease from West Africa, and a history of endemic malaria.[6-7]
SCA is associated with severe clinical and haematological manifestations, including recurrent vaso-occlusive crises, anaemia, neurological, renal, hepatic, growth, and ophthalmological complications,[1] and poor pregnancy outcomes.[8] Individuals with SCT generally do not display the haematological and clinical symptoms of SCA. Indeed, some of them are unaware that they carry the faulty gene; however, there is evidence that they may exhibit complications during stressful situations or life events[9-12] or vigorous physical activities.[13]
Pregnancy is a stressful physiological event, often associated with emotional changes, anxiety, and depression.[14-15] Impact of SCT on pregnancy outcome has been equivocal, with some studies have reported adverse outcomes,[16-27] and contraception has been suggested,[28] whereas others have not.[29-30], also in consideration of greater resistance of carriers to malaria in pregnancy.[29] The reasons for the contradictory findings are not clear. However, factors such as nutritional status before and during pregnancy may play a significant role. Although the prevalence of sickle cell genes in Sudan and other low-income countries like Sub-Saharan African countries is high,[4,31] published data are scarce on pregnancy outcomes in women with SCT.
The aim of the study: is to investigate pregnancy outcomes in Sudanese women with SCT.

Subjects and methods

Subjects. Three hundred sixty-seven (n=367) pregnant women attending their first antenatal appointment during their first trimester at El Obeid Hospital, Kordofan, Western Sudan, were screened for sickle cell gene. Of the 367 women who signed the consent & screened, 34 (n=34) had SCT (HbAS), and the remaining had normal haemoglobin (HbAA). The 34 women with SCT and the 60 (n=60) HbAA, aged 18-40, who fulfilled the inclusion /exclusion criteria and were willing to participate in the study, were selected. The exclusion criteria included those with SCA, thalassemia, other chronic diseases, a physical disability, restricted access to food, and malnourished. In addition, those who were living far from the hospitals were also excluded.
Detailed demographic, obstetric, medical history, dietary habits, and birth outcome data were meticulously documented. A blood sample, 5 ml, was collected at enrolment and delivery (maternal and cord blood). The study was approved by the Ministry of Health of Sudan, the University of Khartoum Medical School, and the London Metropolitan University ethical committees.
Methods. Demography.  In this prospective observational study, a questionnaire was specifically developed to extract participants' obstetric, medical and haematological history data from hospital records.
Anthropometry. Weight and height were assessed using standard measurement methods.
Haematological variables including haemoglobin concentration (Hb), PCV, MCV, mean MCH, and white cell (WBC) and platelet (PLTS) counts were collected. HbS was quantified using a capillary electrophoreses machine (Minicab Sebia flex piercing, Lisses, France).
Statistical analysis. The data are expressed as mean ± standard deviation (sd) or percentages, and the level of statistical significance is set at p<0.05. Quantitative data were tested for normality and homogeneity of variance and subsequently analysed with an independent t-test (parametric data) or Mann–Whitney U test (non-parametric data). Socio-demographic, clinical, and laboratory characteristics data with cells' frequency of five or more were assessed with a chi-square test on the contingency platform. Chi-square, Yate's Correction of Continuity, and Fisher's exact test were used when the observed cell count was less than five (n=5), under the assumption of independence of rows and columns and conditional on the marginal totals. SPSS Statistics for Windows, version 26 (IBM SPSS Ltd., Woking, Surrey, UK) was used to analyse the data.

Results

Demographic and clinical characteristics. Table 1 presents the demographic and clinical characteristics of the women with SCT (HbAS) and normal haemoglobin (HbAA). There was no difference in age, weight, height, or body mass index at baseline between the two groups (p>0.05).
Table 1
Table 1. Mean (± sd) demographic and clinical characteristics of the women with (HbAS, n=34) and without (HbAA, n=60), at baseline (first trimester).
Although SCT women compared with the healthy control group, had lower levels of educational achievements – illiterate and primary (44.1 vs 25.0%; P=0.108), middle and high school (47.1 vs 55.0%; p>0.05) and university (8.8 vs 20.0%; p=0.000) (Table 1); however, the two groups had comparable employment and household income (p=.989) (Table 2). Although it did not reach a level of statistical significance, women with SCT were less likely to own their own house (41.2 vs 60.0%; p=.210) and more likely to live with their relatives (38.2 vs 25.0%; p>0.05) or in rented accommodation (20.6 vs 15.0%; p>0.05).
Table 2
Table 2. Meal frequency, house ownership, and income in Sudanese pounds of the pregnant women with (HbAS, n=34) and without (HbAA, n=60), at enrolment.
The study reveals that consanguineous marriage is still common in Western Sudan, particularly for those with a genetic disorder who are economically disadvantaged. Compared with the control group, there was a higher level of marriage to first and second-degree relatives in the women with SCT (64.7 vs 43.3%; p=.046) and their respective parents (61.8 vs 56.7%; p= .000).
Haematological parameters. At enrolment in the first trimester, the SCT group did not manifest SCA symptoms, and there was no difference in the haematological parameters between the SCT and control groups (Table 3). At delivery (Table 4), women with SCT compared with the control group had lower levels of Hb (p=0.000), PCV (p=0.000), MCH (p=0.002), and neutrophil counts (p=0.045), and higher MCV (p=0.000) and platelet counts (p=0.000). Similarly, at delivery, the babies of SCT women had lower Hb (p= 0.045), PCV (p=0.000), MCH (p=0.000), and higher neutrophil (p=0.004) and platelet (p=0.000) counts (Table 5).
Table 3 Table 3. Mean (± sd) haematological parameters of the women with (HbAS) and without (HbAA) SCT at baseline (first trimester).

Table 4 Table 4. Mean (± sd) haematological parameters of the women with (HbAS) and without (HbAA) SCT at delivery.

Table 5 Table 5. Mean (± sd) haematological parameters of the babies of women with (HbAS) and without (HbAA) SCT at delivery.
Outcome of pregnancy. Birth outcome data are shown in Table 6. The mean birth weight of the babies born to the HbAS mothers was lower than that of the HbAA women's babies (p=0.000). However, there was no difference in head circumference between the babies of the two groups (p>0.05).
Table 6
Table 6. Mean (± sd) birth weight, head circumference, percent SCBU admission and miscarriage of the sickle cell trait (HbAS, n=23) and healthy (HbAA,n= 40) control groups.
Three babies needed admission to the Special Care Baby Unit in the SCT group Vs one in control (13 vs 2.5%, p>0.05). The reason for admissions included neonatal jaundice, low APGAR score, and hypoglycemia at birth. Similarly, the levels of miscarriage or stillbirth were higher in the SCT group (13 vs 2.5%; p>0.05) than in the control group pregnancies.

Discussion

This study investigated maternal and foetal outcomes in pregnancies complicated by SCT in Western Sudan. This region of the country is unique in that it has a high prevalence of SCA that overlaps equally with widespread poverty, malnutrition, illiteracy, and consanguineous marriages.
Similarly consistent with the previous studies,[4,31] the majority of the women with and without SCTs are married to their first or second cousins. However, the number is considerably higher (64.7 vs 43.3%) in the SCT group. In addition, a significant number of the women in the current study had low educational backgrounds (illiterate and primary school level).
Our cohort's HbAS and HbAA pregnant women had equal employment opportunities and comparable earnings, however women were not college educated or/and did not own their homes. Indeed, families affected by SCA may not be able to send their children to a university because of the financial burden associated with higher education. Although the numbers of women with SCT in our cohort were small, the findings were consistent with other observations, indicating that women with HbAS suffer from unemployment, lack of health insurance, and marriage discrimination.[4] Other studies which compared SCTs and healthy controls did not find a difference in socioeconomic status.[28]
The current study revealed that siblings of the HbAS group were more likely to be affected by SCA than their HbAA counterparts (65 vs 13%). A similar observation has been reported in the same region by Munsoor and Alabid.[31] In this region of Sudan, it appears that the tribal habit of marriage among relatives propagates the sickle cell gene. Consanguineous marriage is a factor that supports the spread of the disease.
At baseline, first trimester, the women with and without SCT had comparable weight, height, body mass index, and blood glucose levels. Perhaps this was to be expected, as the two groups had similar meal frequencies (most ate breakfast, lunch, and dinner regularly) and consumed similar types and amounts of foods.
Although the two groups of women had comparable levels of Hb at baseline (first trimester), the SCT group had significantly lower percentages of PCV, MCV, and MCH, probably indicating iron deficiency. A Hb value of less than 11 g/dl during the first and third trimesters is frequently seen, especially in this area of Sudan, with a high prevalence of hunger, malnutrition, and iron deficiency.[32–35]
Consistent with previous reports,[11,18–19] at delivery, this study found significantly lower Hb, PCV percentages, and MCH concentrations in women with SCT compared to their healthy counterparts (HbAA).
Following the recommendation of the WHO,[36] iron and iron-folate tablets are made available free of charge to pregnant women in Sudan.[37] Compliance with iron, folic acid supplementation is related to maternal education level, appropriate antenatal education and care, knowledge about anaemia and iron-folic acid supplements, and regular antenatal care visits.[38–41]
The values of haematological parameters of the babies born to women with SCT and healthy controls closely mirror those of their mothers at delivery, with the Hb, PCV, and MCH levels of the former being significantly lower than those of the latter group, in agreement with earlier studies.[42–43] Therefore, it is evident that maternal SCT had adverse effects on the haematological parameters of their babies. The Hb, PCV, MCV, and MCH values of the babies were significantly lower than those of the neonates of the healthy control group, and the normal cord blood reference ranges reported from Sudan.[44]
Furthermore, babies born to SCT mothers had lower birth weight and a higher chance of admission to the special care baby unit; mothers had more miscarriages and a higher chance of stillbirth than the HbAA group.[25] The reason for admissions to SCABU included neonatal jaundice, low APGAR score, and hypoglycemia at birth. These findings are consistent with other studies, which reported anaemia and neonatal/foetal mortality,[18,20] low birth weight,[20–21] prematurity and pre-eclampsia,[23] intrauterine foetal hypoxia[19] and placental infarction and calcification[20] in pregnancies complicated by SCT.
It is not evident why SCT pregnancy is associated with adverse birth outcomes. Nevertheless, several studies have underscored that iron deficiency and anaemia are risk factors for adverse pregnancy outcomes viz preterm delivery, prematurity, low birth
weight;[34,45–46] placental pathologic changes – infarction and calcification – may also play a role, including its association with increased stillbirth.[20,47]
This study has several limitations, including the relatively small size of SCT patients. Also, due to logistic and financial reasons, reticulocyte count and iron studies could not be determined. In addition, the placentae were not evaluated for pathologic changes (placental infarction or calcification) and postpartum follow-up was not conducted. All of these make affirmative conclusions about causes of stillbirth and other adverse outcomes difficult.

Conclusions

The study revealed that SCT is associated with adverse pregnancy outcomes, including maternal and neonatal anaemia, low birth weight, and increased risk of stillbirth. Therefore, women with SCT who embark on pregnancy should be given appropriate pre-conceptual advice and multidisciplinary antenatal and postnatal care.

Acknowledgements

The authors are grateful to the mothers for graciously consenting to participate in the study, Drs S. Maki and H. Abbakar for conducting obstetric assessments, Sister L. S. Adoom for her work in the delivery room and documentation of birth outcome data, and Mrs F. Eltahir for helping with recruitment and collection of demographic data. Also, we are thankful to Dr O. E. Hassan and Miss K. E. Hassan for facilitating blood samples collection, storage and transport to London and Drs, S. I. Hussein and M. Elshiekh for their valuable advice and guidance throughout the duration of the study.

Authors' contributions

GK conceived the idea, designed and initiated the study and edited the manuscript, AEH. conducted the fieldwork (recruitment, collection of blood samples, data analysis and manuscript drafting), AG helped with the recruitment and collection of demographic data, AS, and MAO, provided valuable advice on SCD and haematology and helped with data evaluation and critical editions of the manuscript, MM, helped with statistical data analysis, AO, and IAK helped with laboratory analysis and AKE facilitated the follow-up with the participants and attended the deliveries.

References   

  1. Ware RE, de Montalembert M, Tshilolo L Abboud MR, sickle cell disease. Lancet. 2017 Jul 15;390(10091):311-323. doi: 10.1016/S0140-6736(17)30193-9. Epub 2017 Feb 1  https://doi.org/10.1016/S0140-6736(17)30193-9 PMid:28159390
  2. Archibald RG. A case of sickle cell anaemia in Sudan. Trans R Soc Trop Med Hyg 1926; 19: 389-39. https://doi.org/10.1016/S0035-9203(26)90485-9
  3. Adam MA, Adam NK, Mohamed BA. Prevalence of sickle cell disease and sickle cell trait among children admitted to Al Fashir Teaching Hospital North Darfur State, Sudan. BMC Research Notes 2019; 12. Available at: https://bmcresnotes. https://doi.org/10.1186/s13104-019-4682-5 PMid:31619285 PMCid:PMC6796395
  4. Daak AA, Elsamani E, Ali EH, et al. Sickle cell disease in western Sudan: genetic epidemiology and predictors of knowledge attitude and practices. Trop Med Int Health 2016; 21:642-653. https://doi.org/10.1111/tmi.12689 PMid:27028397
  5. Sabahelzain MM, Hamamy H. The ethnic distribution of sickle cell disease in Sudan. Pan Afr Med J. 2014 May 3;18:13. https://doi.org/10.11604/pamj.2014.18.13.3280 PMid:25360197 PMCid:PMC4213521
  6. Saha N. · Hamad R.E. Mohamed S.c Inbreeding Effects on Reproductive Outcome in a Sudanese Population. Hum Hered 1990;40:208-212. https://doi.org/10.1159/000153932 PMid:2379925
  7. Luzzatto, L. Sickle Cell Anaemia and Malaria, Mediterranean Journal of Hematology and Infectious Diseases, 2012, 4(1), p. e2012065. https://doi.org/10.4084/mjhid.2012.065 PMid:23170194 PMCid:PMC3499995
  8. Oakley LL, Mitchell S, von Rege I, Hadebe R, Howard J, Robinson SE, Oteng-Ntim E. Perinatal outcomes in women with sickle cell disease: a matched cohort study from London, UK. Br J Haematol. 2021 Dec 8. https://doi.org/10.1111/bjh.17983 PMid:34881428
  9. Yeral M , Boğa C. Is Sickle Cell Trait Really Innocent?. Turk J Haematol. 2021 Jun 1;38(2):159-160. https://doi.org/10.4274/tjh.galenos.2020.2020.0344 PMid:33053967 PMCid:PMC8171209
  10. Abdulsalam, A. A., Bashour, H. N., Monem, F. S, Hamadeh FM, Pregnancy outcome among Palestinian refugee women with sickle cell trait in Damascus, Syria. Saudi Med J. 2003 Sep;24(9):986-90.
  11. Adam, I., Ibrahim, Y., Elhardello, O. (2018). Prevalence, types and determinants of anemia among pregnant women in Sudan: A systematic review and meta-analysis, BMC Hematol, vol. 18, no. 31. https://doi.org/10.1186/s12878-018-0124-1 PMid:30455961 PMCid:PMC6225563
  12. Adam, M. A., Adam, N. K., Mohamed, B. A. (2019) 'Prevalence of sickle cell disease and sickle cell trait among children admitted to Al Fashir Teaching Hospital North Darfur State, Sudan', BMC Research Notes, vol. 12, p. 659. https://doi.org/10.1186/s13104-019-4682-5 PMid:31619285 PMCid:PMC6796395
  13. Adeyemi, A. B., Adediran, I. A., Kuti, O., Owolabi, A. T., Durosimi, M. A. (2009) 'Outcome of pregnancy in a population of Nigerian women with sickle cell trait', J Obstet Gynaecol, vol. 26, no. 2, pp. 133-137. https://doi.org/10.1080/01443610500443428 PMid:16483970
  14. Naik RP, Haywood C Jr. Sickle cell trait diagnosis: clinical and social implications. Hematology Am Soc Hematol Educ Program. 2015;2015(1):160-7. https://doi.org/10.1182/asheducation-2015.1.160 PMid:26637716 PMCid:PMC4697437
  15. de Weerth C, Buitelaar JK. Physiological stress reactivity in human pregnancy - a review. Neurosci Biobehav Rev. 2005 Apr;29(2):295-312. https://doi.org/10.1016/j.neubiorev.2004.10.005 PMid:15811500
  16. Bjelica A, Cetkovic N, Trninic-Pjevic A, Mladenovic-Segedi L. The phenomenon of pregnancy - a psychological view. Ginekol Pol. 2018;89(2):102-106. https://doi.org/10.5603/GP.a2018.0017 PMid:29512815
  17. O'Hara C, Singer DE, Niebuhr DW. The Risk of Pregnancy Related Hypertension Disorder Associated with Sickle Cell Trait in U.S. Service Women. Mil Med. 2020 Feb 12;185(1-2):e183-e190. https://doi.org/10.1093/milmed/usz143 PMid:31247087 PMCid:PMC7413597
  18. Ugboma HAA, George IO. Sickle Cell Disease in Pregnancy: Maternal and Fetal Outcome in Port Harcourt, Nigeria. J Adv Med Medical Res. 2015; 7(1): 40-44. https://doi.org/10.9734/BJMMR/2015/11602 PMid:26111969
  19. Hamdi IM, Kamakshi S K, Ghani EA. Pregnancy outcome in women with sickle cell trait. Saudi Med J. 2002 Dec;23(12):1455-7.
  20. Manzar. S Maternal sickle cell trait and fetal hypoxia. Am J Perinatol. 2000;17(7):367-70. https://doi.org/10.1055/s-2000-13444 PMid:12141523
  21. Taylor MY, Wyatt-Ashmead J, Gray J, Bofill JA, Martin R, Morrison JC. Pregnancy loss after first-trimester viability in women with sickle cell trait: time for a reappraisal?. Am J Obstet Gynecol. 2006 Jun;194(6):1604-8. https://doi.org/10.1016/j.ajog.2006.02.027 PMid:16635469
  22. Hoff C, Wertelecki W, Dutt J, Hernandez R, Reyes E, Sharp M. Sickle cell trait, maternal age and pregnancy outcome in primiparous women. Hum Biol. 1983 Dec;55(4):763-70.
  23. Rathod, K. B., Jaiswal, K. N., Shrivastava, A. C., Shrikhande, A. V. (2007) 'Study of the placenta in sickle cell disorders', Indian J Pathol Microbiol. 2007 Oct;50(4):698-701.
  24. Wilson, S., Ellsworth, P., Key, N. S. Pregnancy in sickle cell trait: What we do and don't know', Br J Haematol. 2020 Aug;190 (3):328-335. https://doi.org/10.1111/bjh.16518 PMid:32064587 PMCid:PMC7415474
  25. Canelón SP, Butts S, Boland MR, Evaluation of Stillbirth Among Pregnant People with Sickle Cell Trait. JAMA Netw Open. 2021 Nov 1;4(11): e2134274. https://doi.org/10.1001/jamanetworkopen.2021.34274 PMid:34817585 PMCid:PMC8613600
  26. Jain D., Atmapoojya P., Colah R.,Lodha P.Sickle cell disease and pregnancy. Mediterr J Hematol Infect Dis 2019, 11(1): e2019040, https://doi.org/10.4084/mjhid.2019.040  PMid:31308916 PMCid:PMC6613624
  27. Wellenstein WL, Sullivan S, Darbinian J, Weintraub MLR, Greenberg M, Adverse Pregnancy Outcomes in Women with Sickle Cell Trait. AJP Rep. 2019 Oct;9(4):e346-e352. https://doi.org/10.1055/s-0039-1695743 PMid:31723455 PMCid:PMC6847694
  28. de Sanctis V., Soliman A.T., Daar S., Canatan D., Di Maio S., Kattamis C.Current issues and options for hormonal contraception in adolescents and young adult women with sickle cell disease: an update for health care professionals.Mediterr J Hematol Infect Dis 2020, 12(1): e2020032 https://doi.org/10.4084/mjhid.2020.032 PMid:32395221 PMCid:PMC7202337
  29. Adeyemi AB, Adediran IA, Kuti O, Owolabi AT, Durosimi MA. Outcome of pregnancy in a population of Nigerian women with sickle cell trait. J Obstet Gynaecol. 2006 Feb;26(2):133-7. https://doi.org/10.1080/01443610500443428 PMid:16483970
  30. Baill IC, Witter FR. Sickle trait and its association with birthweight and urinary tract infections in pregnancy. Int J Gynaecol Obstet. 1990 Sep;33(1):19-21. https://doi.org/10.1016/0020-7292(90)90649-6 PMid:1974527
  31. Munsoor, M. M., Alabid, A. SCT among relatives of sickle cell patients in Western Sudan. Canad. J. Med, 2011; 2 (2): 20-25.
  32. Kadry S, Sleem C, Samad RA. Hemoglobin levels in pregnant women and its outcomes. Biom Biostat Int J. 2018;7(4):326-336.
  33. Solomon, Y., Sema, A., Menberu, T. Adherence and associated factors to iron and folic acid supplementation among pregnant women attending antenatal care in public hospitals of Dire Dawa, Eastern Ethiopia. Eur J Midwifery. 2021 Aug 25;5:35. https://doi.org/10.18332/ejm/138595 PMid:34514359 PMCid:PMC8386124
  34. Tarekegn, M., Wubshet, M., Atenafu, A., Derso, T., Woretaw, A. Antenatal care and mothers' education improved iron-folic acid adherence at Denbiya district health centers, Northwest Ethiopia: using pills count method. Arch Public Health. 2019 Jun 25;77:30. https://doi.org/10.1186/s13690-019-0356-y PMid:31285822 PMCid:PMC6591834
  35. Gebremariam, A. D., Tiruneh, S. A., Abate, B. A., Engidaw, M. T., Asnakew, D. T. Adherence to iron with folic acid supplementation and its associated factors among pregnant women attending antenatal care follow up at Debre Tabor General Hospital, Ethiopia, 2017. PLoS One. 2019 Jan 7;14(1):e0210086. https://doi.org/10.1371/journal.pone.0210086 PMid:30615646 PMCid:PMC6322725
  36. Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-Urrutia MC, Dowswell T. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015 Oct 19;2015(10):CD009997. https://doi.org/10.1002/14651858.CD009997.pub2
  37. Abdullahi H, Gasim GI, Saeed A, Imam AM, Adam I. Antenatal iron and folic acid supplementation use by pregnant women in Khartoum, Sudan. BMC Res Notes. 2014 Aug 7;7:498. https://doi.org/10.1186/1756-0500-7-498 PMid:25099760 PMCid:PMC4132242
  38. Dapper DV, Didia BC. Haemorheological parameters of umbilical cord blood of Nigerian newborns: correlations with maternal parameters. West Afr J Med. Jul-Sep 2006;25(3):226-30. https://doi.org/10.4314/wajm.v25i3.28283 PMid:17191424
  39. Sanni OB, Chambers T, Li JH , Rowe S , Woodman AG , Ospina MB, Bourque SL. A systematic review and meta-analysis of the correlation between maternal and neonatal iron status and haematologic indices. EClinical Medicine. 2020 Oct 8;27:100555. https://doi.org/10.1016/j.eclinm.2020.100555 PMid:33205030 PMCid:PMC7648126
  40. Angelo A, Derbie G, Demtse A, Tsegaye A, Umbilical cord blood hematological parameters reference interval for newborns from Addis Ababa, Ethiopia. BMC Pediatr. 2021 Jun 11 ;21 (1):275. https://doi.org/10.1186/s12887-021-02722-z PMid:34116664 PMCid:PMC8194248
  41. Snook J, Bhala N, Beales ILP, Cannings D, Kightley C, Logan RPH, Pritchard DM, Sidhu R, Surgenor S,Thomas W, Verma AM, Goddard AF, British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut 2021;0:1-22. https://doi.org/10.1136/gutjnl-2021-325210 PMid:34497146 PMCid:PMC8515119
  42. Baill, I. C., Witter, F. R. Sickle trait and its association with birthweight and urinary tract infections in pregnancy. Int J Gynaecol Obstet. 1990 Sep;33(1):19-21. https://doi.org/10.1016/0020-7292(90)90649-6 PMid:1974527
  43. Barfield, W. D., Barradas, D. T., Manning, S. E., Kotelchuck, M., Shapiro-Mendoza, C. K.. Sickle cell disease and pregnancy outcomes: women of African descent. Am J Prev Med. 2010 Apr;38(4 Suppl):S542-9. https://doi.org/10.1016/j.amepre.2009.12.020 PMid:20331956
  44. Elgari, M., Waggiallah, H. A. Cord blood hematological profile of Sudanese neonates at birth in Khartoum State. National Journal of Integrated Research in Medicine, 2014; 5(4):22-25. eISSN: 0975-9840 pISSN: 2230 - 9969
  45. Dapper D V, Didia B C. Haemorheological parameters of umbilical cord blood of Nigerian newborns: Correlations with maternal parameters. West Afr J Med. Jul-Sep 2006 ;25(3):226-30. https://doi.org/10.4314/wajm.v25i3.28283 PMid:17191424
  46. De Weerth C, Buitelaar J. K. Physiological stress reactivity in human pregnancy - A review. Neurosci Biobehav Rev. 2005 Apr;29(2):295-312. https://doi.org/10.1016/j.neubiorev.2004.10.005 PMid:15811500
  47. El-Hazmi MAF, Al-Hazmi AM, Warsy AS. Sickle cell disease in Middle East Arab countries. Indian J Med Res. 2011 Nov;134(5):597-610. https://doi.org/10.4103/0971-5916.90984 PMid:22199098 PMCid:PMC3249957


[TOP]