Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

Jennifer B Griffin, Victor Lokomba, Sarah H Landis, John M Thorp Jr, Amy H Herring, Antoinette K Tshefu, Stephen J Rogerson, Steven R Meshnick, Jennifer B Griffin, Victor Lokomba, Sarah H Landis, John M Thorp Jr, Amy H Herring, Antoinette K Tshefu, Stephen J Rogerson, Steven R Meshnick

Abstract

Background: During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks' gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction.

Methods: Data were analysed from 548 antenatal visits after 20 weeks' gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction.

Results: There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia.

Conclusions: Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.

Figures

Figure 1
Figure 1
Time plot of mean uterine and umbilical artery resistance index against gestational age. Population average smoothed trend line (in black) (n = 128, with 544 visits). Kinshasa, Democratic Republic of Congo, 2005–2006. A. Uterine artery resistance index against gestational age in weeks. B. Umbilical artery resistance index against gestational age in weeks.
Figure 2
Figure 2
Population average growth curves for uterine artery resistance index by early pregnancy malaria parasitaemia exposure. Kinshasa, Democratic Republic of Congo, 2005–2006. A. The unadjusted effect of early pregnancy malaria parasitaemia on mean uterine artery resistance index (n = 547 visits). B. The adjusted effect of early pregnancy malaria parasitaemia on mean uterine artery resistance index by maternal mid-upper arm circumference (MUAC). Model adjusted for gravidity and foetal sex; product interaction term (early pregnancy malaria parasitaemia * low MUAC) -2LL test p = 0.026, with 1 df (n = 544 visits). The overall standard deviation for uterine artery resistance index was 0.089.
Figure 3
Figure 3
Population average growth curves for umbilical artery resistance index by early pregnancy malaria parasitaemia exposure. Kinshasa, Democratic Republic of Congo, 2005–2006. A. The unadjusted effect of early pregnancy malaria parasitaemia on umbilical artery resistance index (n = 547 visits). B. The adjusted effect of early pregnancy malaria parasitaemia on umbilical artery resistance index by gravidity. Model adjusted for foetal sex and low education; interaction terms: (early pregnancy malaria parasitaemia * gestational age in weeks) -2LL test p = 0.025; (early pregnancy malaria parasitaemia * primigravidae) -2LL test p = 0.025, with 1 df (n = 540 visits). The overall standard deviation for UA RI was 0.089.

References

    1. A Strategic Framework for Malaria Prevention and Control During. Pregnancy in the African Region. WHO Regional Office for Africa, Brazzaville; 2004. URL: .
    1. O'Dowd MJ, O'Dowd TM. Quickening—a re-evaluation. Br J Obstet Gynaecol. 1985;92:1037–1039. doi: 10.1111/j.1471-0528.1985.tb02999.x.
    1. Brabin BJ. An analysis of malaria in pregnancy in Africa. Bull World Health Organ. 1983;61:1005–1016.
    1. Prefumo F, Sebire NJ, Thilaganathan B. Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices. Hum Reprod. 2004;19:206–209. doi: 10.1093/humrep/deh037.
    1. Sebire NJ, Sepulveda W. Correlation of placental pathology with prenatal ultrasound findings. J Clin Pathol. 2008;61:1276–1284. doi: 10.1136/jcp.2008.055251.
    1. Trudinger BJ, Giles WB, Cook CM. Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy. Br J Obstet Gynaecol. 1985;92:39–45. doi: 10.1111/j.1471-0528.1985.tb01046.x.
    1. Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery flow velocity waveforms and placental resistance: pathological correlation. Br J Obstet Gynaecol. 1985;92:31–38. doi: 10.1111/j.1471-0528.1985.tb01045.x.
    1. Trudinger BJ, Giles WB, Cook CM, Bombardieri J, Collins LEE. Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. Br J Obstet Gynaecol. 1985;92:23–30.
    1. Dorman EK, Shulman CE, Kingdom J, Bulmer JN, Mwendwa J, Peshu N, Marsh K. Impaired uteroplacental blood flow in pregnancies complicated by falciparum malaria. Ultrasound Obstet Gynecol. 2002;19:165–170. doi: 10.1046/j.0960-7692.2001.00545.x.
    1. Landis SH. A longitudinal ultrasound study of fetal growth and intrauterine growth restriction in Kinshasa. Democratic Republic of Congo. Dissertation. University of North Carolina, Epidemiology; 2007.
    1. Landis SH, Lokomba V, Ananth CV, Atibu J, Ryder RW, Hartmann KE, Thorp JM, Tshefu A, Meshnick SR. Impact of maternal malaria and under-nutrition on intrauterine growth restriction: a prospective ultrasound study in Democratic Republic of Congo. Epidemiol Infect. 2009;137:294–304. doi: 10.1017/S0950268808000915.
    1. Taylor SM, Juliano JJ, Trottman PA, Griffin JB, Landis SH, Kitsa P, Tshefu AK, Meshnick SR. High-throughput pooling and real-time PCR-based strategy for malaria detection. J Clin Microbiol. 2010;48:512. doi: 10.1128/JCM.01800-09.
    1. Ohrt C, Obare P, Nanakorn A, Adhiambo C, Awuondo K, O'Meara W, Remich S, Martin K, Cook E, Chretien J-P, Lucas C, Osoga J, McEvoy P, Owaga ML, Odera JS, Ogutu B. Establishing a malaria diagnostics centre of excellence in Kisumu. Kenya. Malar J. 2007;6:79.
    1. Maulik D. In: Doppler Ultrasound in Obstetrics and Gynecology. 2nd rev. and enlarged ed. edition. Maulik DZ, Zalud I, editor. Springer-Verlag, Berlin Heidelberg; 2005. Spectral Doppler Sonography: waveform analysis and hemodynamic interpretation; pp. 35–56.
    1. Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology. 1991;181:129–133.
    1. Johnsen SL, Rasmussen S, Wilsgaard T, Sollien R, Kiserud T. Longitudinal reference ranges for estimated fetal weight. Acta Obstet Gynecol Scand. 2006;85:286–297. doi: 10.1080/00016340600569133.
    1. Landis SH, Ananth CV, Lokomba V, Hartmann KE, Thorp JM Jr, Horton A, Atibu J, Ryder RW, Tshefu A, Meshnick SR. Ultrasound derived fetal size nomogram for a sub Saharan African population: a longitudinal study. Ultrasound Obstet Gynecol. 2009;34:379–386. doi: 10.1002/uog.6357.
    1. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology. 1984;152:497–501.
    1. Mongelli M, Wilcox M, Gardosi J. Estimating the date of confinement: ultrasonographic biometry versus certain menstrual dates. Am J Obstet Gynecol. 1996;174:278–281. doi: 10.1016/S0002-9378(96)70408-8.
    1. Krasovec K, Anderson MA. Maternal nutrition and pregnancy outcomes: anthropometric assessment. Washington, DC: Pan American Health Organization, Pan American Sanitary Bureau, Regional Office of the World Health Organization; 1991.
    1. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982;38:963–974. doi: 10.2307/2529876.
    1. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986;73:13. doi: 10.1093/biomet/73.1.13.
    1. Fitzmaurice GM. Longitudinal data analysis. Chapman & Hall/CRC, Boca Raton, FL; 2009.
    1. Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, Newman RD. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007;7:93–104. doi: 10.1016/S1473-3099(07)70021-X.
    1. Rogerson SJ, Hviid L, Duffy PE, Leke RF, Taylor DW. Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis. 2007;7:105–117. doi: 10.1016/S1473-3099(07)70022-1.
    1. Rijken MJ, Papageorghiou AT, Thiptharakun S, Kiricharoen S, Dwell SLM, Wiladphaingern J, Pimanpanarak M, Kennedy SH, Nosten F, McGready R. Ultrasound evidence of early fetal growth restriction after maternal malaria infection. PLoS One. 2012;7:e31411. doi: 10.1371/journal.pone.0031411.
    1. Arbeille P, Carles G, Bousquet F, Body G, Lansac J. Fetal cerebral and umbilical artery blood flow changes during pregnancy complicated by malaria. J Ultrasound Med. 1998;17:223–229.
    1. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension. Science. 1997;277:1669. doi: 10.1126/science.277.5332.1669.
    1. Ordi J, Menendez C, Ismail MR, Ventura PJ, Palacín A, Kahigwa E, Ferrer B, Cardesa A, Alonso PL. Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells. J Infect Dis. 2001;183:1100. doi: 10.1086/319295.
    1. Yui J, Garcia-Lloret M, Wegmann TG, Guilbert LJ. Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placenta. 1994;15:819–835. doi: 10.1016/S0143-4004(05)80184-5.
    1. Renaud SJ, Postovit LM, Macdonald-Goodfellow SK, McDonald GT, Caldwell JD, Graham CH. Activated macrophages inhibit human cytotrophoblast invasiveness in vitro. Biol Reprod. 2005;73:237. doi: 10.1095/biolreprod.104.038000.
    1. Williams PJ, Bulmer JN, Innes BA, Broughton Pipkin F. Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy. Biol Reprod. 2011;84:1148–1153. doi: 10.1095/biolreprod.110.088351.
    1. Brabin BJ, Alexander Fletcher K, Brown N. Do disturbances within the folate pathway contribute to low birth weight in malaria? Trends Parasitol. 2003;19:39–43. doi: 10.1016/S1471-4922(02)00004-1.
    1. Conroy AL, McDonald CR, Silver KL, Liles WC, Kain KC. Complement activation: a critical mediator of adverse fetal outcomes in placental malaria? Trends Parasitol. 2011;27:294–299. doi: 10.1016/j.pt.2011.02.005.
    1. Girardi G, Bulla R, Salmon JE, Tedesco F. The complement system in the pathophysiology of pregnancy. Mol Immunol. 2006;43:68–77. doi: 10.1016/j.molimm.2005.06.017.
    1. Burton GJ, Jauniaux E, Charnock-Jones DS. The influence of the intrauterine environment on human placental development. Int J Dev Biol. 2010;54:303–312. doi: 10.1387/ijdb.082764gb.
    1. Belkacemi L, Nelson DM, Desai M, Ross MG. Maternal undernutrition influences placental-fetal development. Biol Reprod. 2010;83:325–331. doi: 10.1095/biolreprod.110.084517.
    1. Roberts CT. IFPA Award in Placentology Lecture: Complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health. Placenta. 2010;31:S47–S53.
    1. Myatt L. Placental adaptive responses and fetal programming. J Physiol. 2006;572:25–30.
    1. Landis SH. A longitudinal ultrasound study of fetal growth and intrauterine growth restriction in Kinshasa, Democratic Republic of Congo. Chapel Hill: The University of North Carolina; 2008.
    1. Muehlenbachs A, Mutabingwa TK, Edmonds S, Fried M, Duffy PE. Hypertension and maternal-fetal conflict during placental malaria. PLoS Med. 2006;3:e446. doi: 10.1371/journal.pmed.0030446.
    1. Abramowicz JS, Sheiner E. Ultrasound of the placenta: a systematic approach. Part II: Functional assessment (Doppler) Placenta. 2008;29:921–929. doi: 10.1016/j.placenta.2008.08.010.
    1. Kingdom JCP, Kaufmann P. Oxygen and placental villous development: Origins of fetal hypoxia. Placenta. 1997;18:613–621. doi: 10.1016/S0143-4004(97)90000-X.
    1. Jackson MR, Mayhew TM, Haas JD. Morphometric studies on villi in human term placentae and the effects of altitude, ethnic grouping and sex of newborn. Placenta. 1987;8:487–495. doi: 10.1016/0143-4004(87)90077-4.
    1. Pfarrer C, Macara L, Leiser R, Kingdom J. Adaptive angiogenesis in placentas of heavy smokers. Lancet. 1999;354:303. doi: 10.1016/S0140-6736(99)01676-1.
    1. Kadyrov N, Kosanke G. Increased fetoplacental angiogenesis during first trimester in anaemic women. Lancet. 1998;352:1747–1749. doi: 10.1016/S0140-6736(98)02069-8.
    1. Cao Y, Linden P, Shima D, Browne F, Folkman J. In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor. J Clin Invest. 1996;98:2507. doi: 10.1172/JCI119069.
    1. Brabin BJ, Romagosa C, Abdelgalil S, Menendez C, Verhoeff FH, McGready R, Fletcher KA, Owens S, D'Alessandro U, Nosten F. et al.The sick placenta-the role of malaria. Placenta. 2004;25:359–378. doi: 10.1016/j.placenta.2003.10.019.
    1. Cottrell G, Mary JY, Barro D, Cot M. The importance of the period of malarial infection during pregnancy on birth weight in tropical Africa. AmJTrop Med Hyg. 2007;76:849.
    1. Huynh BT FN, Gbaguidi G, Dechavanne S, Borgella S, Guezo-Mevo B, Massougbodji A, Ndam N, Deloron P, Cot M. Influence of the timing of malaria infection during pregnancy on birth weight and on maternal anaemia in Benin. AmJTrop Med Hyg. 2011;85:214–220.
    1. Kalilani L, Mofolo I, Chaponda M, Rogerson SJ, Meshnick SR. The effect of timing and frequency of Plasmodium falciparum infection during pregnancy on the risk of low birth weight and maternal anemia. Trans R Soc Trop Med Hyg. 2010;104:416–422. doi: 10.1016/j.trstmh.2010.01.013.
    1. Taha TET, Gray RH, Mohamedani AA. Malaria and low birth weight in central Sudan. Am J Epidemiol. 1993;138:318.
    1. Fried M, Muga RO, Misore AO, Duffy PE. Malaria elicits type 1 cytokines in the human placenta: IFN-{gamma} and TNF-{alpha} associated with pregnancy outcomes. J Immunol. 1998;160:2523.
    1. Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, Font F, Alonso PL. The impact of placental malaria on gestational age and birth weight. J Infect Dis. 2000;181:1740–1745. doi: 10.1086/315449.

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