Preterm births are a leading cause of death in under five worldwide. World Health Organization (WHO) defines it as births that occur after 20 weeks and before 37 weeks of gestation. Preterm births can either be spontaneous or induced/ iatrogenic and afflict about 15 million children every year, one million or whom die. Bacterial infections are hypothesized to increase the risk of preterm labour and birth. However, bacterial species associated with such outcomes are poorly described.
REVIEW OF LITERATURE
According to the World Health Organization (WHO), preterm birth refers to any birth that occurs before 37 weeks of completed gestations, and is further divided into three levels (moderate or late preterm (32–<37 weeks), very preterm (28–<32 weeks), and extremely preterm (<28 weeks) based on gestation. It is a common occurrence globally with close to 15 million neonates thought to be afflicted (1). Of the 15 million cases, more than 84% of cases are moderate or late preterm, while approximately 10% and 5% of cases are often very preterm and extremely preterm respectively (2).
The prevalence of preterm birth is 5-18% globally with Nigeria, India, United States, China, Indonesia, and Pakistan, accounting for 50% of cases (3). In Low to Middle Income Countries, 60% of preterm births are in Sub-Saharan Africa, while 12.8% are south Asia (4). In Kenya, the prevalence of preterm births was estimated to be 18.8% in a maternal unit in 2018 (5) and around 20.2% in a post-natal ward in 2017 (6). In country estimates put the overall prevalence of preterm birth in Kenya at around 13.1%-18.5% (7), which is slightly higher than in Uganda where 13.7%-14.4% of all births are preterm (7,8) and Tanzania where 14.3% of all births are preterm (9).
While the efforts instituted to prolong labour and prevent preterm labor and birth have been effective, a few gaps still exist in resource limited areas such as Kenya. Bacterial infections have been shown to increase the risk preterm labor and birth in epidemiological and experimental human research and in animal models. However, data on the bacterial species possibly associated with preterm labor and preterm birth is limited in Kenya. Its possible association with preterm births among women with spontaneous preterm births with ruptured membranes has not been evaluated.
Labor is preterm when the cervix opens with regular contractions after week 20 of gestation and before 37 weeks (10). The condition is popular among women with a short cervix and a history of gynecological complications, and can be spontaneous or provider initiated/induced. Spontaneous premature labor commences naturally with pre-ruptured or intact membranes despite efforts to prolong pregnancies, and is the commonest type at 65-75% of all cases. Induced or provider initiated preterm labor commences after a medical intervention necessitated by adverse maternal or fetal complications such as preeclampsia or fetal growth restriction, and accounts for 30-35% of cases (11). Among affected women, premature birth is the main endpoint for spontaneous and induced labor – a risk factor for perinatal mortality and morbidity.
According to the World Health Organization (WHO), preterm birth refers to any birth that occurs before a baby reaches 37 weeks of completed gestations, and is further divided into three levels (moderate or late preterm (32–<37 weeks), very preterm (28–<32 weeks), and extremely preterm (<28 weeks) based on gestation. It is a common occurrence globally with close to 15 million neonates thought to be afflicted (1). Of the 15 million cases, more than 84% of cases are moderate or late preterm, while about 10% and 5% of cases are very preterm and extremely preterm respectively (2).
Preterm birth is a leading cause of mortality and morbidity in under-fives worldwide. In 2015, preterm births were associated with about 1.055 million deaths of neonates (95% CI=0·935–1·179), way ahead of pneumonia at 0·921 million and intrapartum-related events at 0·691 million (12). By 2020, as much as 35% of all neonatal deaths were as a result of preterm births as the principle cause or as a contributory factor, making it an important public health problem that warrants immediate attention (2).
The prevalence of preterm birth is 5-18% globally with six countries, namely Nigeria, India, the United States, China, Indonesia, and Pakistan, accounting for 50% of cases (3). Low- and Medium-Income Countries (LMIC), mostly in sub-Saharan Africa and South East Asia, are disproportionately affected. According to Blencowe et al., over 60% of preterm births are reported in Sub-Saharan Africa, while 12.8% occur in south Asia (4). In Kenya, a 2018 cross-sectional study of 322 mothers admitted at the maternity unit of Kenyatta National Hospital (KNH) found the prevalence of preterm births to be 18.8% with antepartum hemorrhage, pregnancy induced hypertension, and prolonged pre labour rupture of membranes identified as risk factors (5). The prevalence was slightly higher in a post-natal ward at KNH (20.2%) in a cross-sectional study by Okubatsion and others in 2017 (6) , while the overall in country estimates published by Miller et al., put the prevalence of preterm birth in Kenya at 13.1%-18.5% (7). The rate is slightly higher than in Uganda where 13.7%-14.4% of all births are preterm (7,8) and in Tanzania where about 14.3% of all births are preterm (9).
Older maternal age, maternal stress and gynecological and obstetric factors such as interpregnancy latency and history of preterm labor and well known risk factors for preterm labor (13,14). However, there is growing evidence of an association between bacterial infection and commencement of labor prematurely, even though data from Africa is limited. In a 2011 review titled “Intrauterine infection and preterm labor” published by Agrawal and Hirsch, in Seminars in Fetal & Neonatal Medicine journal, the authors postulated that at least 40% of preterm births reported all over the world might be the result of an intrauterine infection (15). According to the authors, toll like receptors in the uterine cavity detect a broad spectrum of bacterial pathogens and initiate a non-adaptative pro-inflammatory cascade with chemokines, cytokines, and prostaglandins that rupture fetal membranes and induce early fetal contraction.
Such molecular mechanisms linking bacterial infection to preterm labor and birth have been elucidated in experimental studies as well. In an infection and labour study of 264 patients with preterm labor and intact membranes seen at the Yale-New Haven Hospital in the United States in 1989, Romero et al. demonstrated a strong association between infection and labor progression. From the data, microbiological colonization and the probability of detecting inflammatory cytokines were higher among women in preterm labor compared to those who were not in labor. Moreover, all patients who had a bacterial endotoxin in amniotic fluid delivered a preterm baby. Ureaplasma urealyticum, Fusobacterium species, and Mycoplasma hominis were the most frequently isolated bacterial species among the parturients studied. In another study by Fan et al. in New Orleans, 107 episodes of pyelonephritis were associated with the early puerperium or pregnancy (16), while Benedetti et al. and Xiong et al. shown an association between antepartum pneumonia and occurrence of preterm labor and periodontal disease and occurrence of preterm labor respectively (17,18).
These findings have been replicated in animal models as well. Bennett et al. studied the effect of bacterial infection on pregnancy by infusing an intrauterine endotoxin (lipopolysaccharide) in pregnant rats. Overall, rats that received the endotoxin had a significantly shorter interval to labor and delivery compared to controls and showed higher levels of placental prostaglandin F2alpha metabolites (19). In another study, infusion of bacterial toll-like receptor ligands amplified inflammatory response and nitric oxide synthase in gravid mice, and increased incidence of preterm labor (20). Unfortunately, while the molecular mechanisms elucidating the association between bacterial infection and labor progression are, to a great extent, well elucidated, the diversity of bacterial pathogens causing spontaneous labor and premature delivery among women with ruptured membranes has not been studied in-depth in Kenya.
At Kenyatta National Hospital, Amenge James, evaluated “the prevalence of bacteria in intraamniotic infections in spontaneous labor with intact membranes” in a hospital based exploratory cross-sectional study in 2019 (21). In the study, bacterial species, mainly Enterococcus faecalis and Staphylococcus epidermis, were isolated from two out of 22 samples, translating to a prevalence of 9%. However, because of the small sample size and limited scope of the study, causation could not be established. Also, because birth outcomes of parturients were not evaluated, prevalence of preterm births arising from bacterial infection of the uterus of parturients was not evaluated.
The prevalence of preterm labor and births has been approximated to reach 20% in maternity units and postnatal wards in Kenya. This increases the risk of perinatal or neonatal mortality and impeded visual, cognitive, and motor development whenever a child survives. While the efforts instituted to prolong labour and prevent preterm labor and birth have been effective, a few gaps still exist in resource limited areas such as Kenya, which can have a negative bearing on management. While the link between bacterial infections and risk preterm labor and delivery have been shown in epidemiological and experimental human research and in animal models, data on the bacterial species possibly associated with preterm labor and preterm birth is limited in Kenya. Amenge James detected bacterial cultures in 9% of women with spontaneous preterm birth with intact membranes (21) but failed to assess probable link with preterm births. Also, women with ruptured membranes were not evaluated.
REFERENCES
1. World Health Organization. Preterm birth [Internet]. [cited 2021 May 2]. Available from: https://www.who.int/news-room/fact-sheets/detail/preterm-birth
2. Walani SR. Global burden of preterm birth. International Journal of Gynecology & Obstetrics. 2020;150(1):31–3.
3. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller A-B, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162–72.
4. Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller A-B, et al. Born Too Soon: The global epidemiology of 15 million preterm births. Reprod Health. 2013 Nov 15;10(Suppl 1):S2.
5. Wagura P, Wasunna A, Laving A, Wamalwa D, Ng’ang’a P. Prevalence and factors associated with preterm birth at kenyatta national hospital. BMC Pregnancy and Childbirth. 2018 Apr 19;18(1):107.
6. Okube OT, Sambu LM. Determinants of Preterm Birth at the Postnatal Ward of Kenyatta National Hospital, Nairobi, Kenya. Open Journal of Obstetrics and Gynecology. 2017 Aug 30;7(9):973–88.
7. Miller L, Wanduru P, Santos N, Butrick E, Waiswa P, Otieno P, et al. Working with what you have: How the East Africa Preterm Birth Initiative used gestational age data from facility maternity registers. PLOS ONE. 2020 Aug 31;15(8):e0237656.
8. Otieno P, Waiswa P, Butrick E, Namazzi G, Achola K, Santos N, et al. Strengthening intrapartum and immediate newborn care to reduce morbidity and mortality of preterm infants born in health facilities in Migori County, Kenya and Busoga Region, Uganda: a study protocol for a randomized controlled trial. Trials. 2018 Jun 5;19(1):313.
9. Temu TB, Masenga G, Obure J, Mosha D, Mahande MJ. Maternal and obstetric risk factors associated with preterm delivery at a referral hospital in northern-eastern Tanzania. Asian Pacific Journal of Reproduction. 2016 Sep 1;5(5):365–70.
10. Georgiou HM, Di Quinzio MKW, Permezel M, Brennecke SP. Predicting Preterm Labour: Current Status and Future Prospects. Disease Markers. 2015 Jun 15;2015:e435014.
11. Deressa AT, Cherie A, Belihu TM, Tasisa GG. Factors associated with spontaneous preterm birth in Addis Ababa public hospitals, Ethiopia: cross sectional study. BMC Pregnancy and Childbirth. 2018 Aug 13;18(1):332.
12. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. The Lancet. 2016 Dec 17;388(10063):3027–35.
13. Chang Y-K, Tseng Y-T, Chen K-T. The epidemiologic characteristics and associated risk factors of preterm birth from 2004 to 2013 in Taiwan. BMC Pregnancy and Childbirth. 2020 Apr 6;20(1):201.
14. Cobo T, Kacerovsky M, Jacobsson B. Risk factors for spontaneous preterm delivery. International Journal of Gynecology & Obstetrics. 2020;150(1):17–23.
15. Agrawal V, Hirsch E. Intrauterine infection and preterm labor. Semin Fetal Neonatal Med. 2012 Feb;17(1):12–9.
16. Fan YD, Pastorek JG, Miller JM, Mulvey J. Acute pyelonephritis in pregnancy. Am J Perinatol. 1987 Oct;4(4):324–6.
17. Benedetti TJ, Valle R, Ledger WJ. Antepartum pneumonia in pregnancy. Am J Obstet Gynecol. 1982 Oct 15;144(4):413–7.
18. Xiong X, Buekens P, Fraser WD, Beck J, Offenbacher S. Periodontal disease and adverse pregnancy outcomes: a systematic review. BJOG. 2006 Feb;113(2):135–43.
19. Bennett WA, Terrone DA, Rinehart BK, Kassab S, Martin JN, Granger JP. Intrauterine endotoxin infusion in rat pregnancy induces preterm delivery and increases placental prostaglandin F2alpha metabolite levels. Am J Obstet Gynecol. 2000 Jun;182(6):1496–501.
20. Ilievski V, Hirsch E. Synergy between viral and bacterial toll-like receptors leads to amplification of inflammatory responses and preterm labor in the mouse. Biol Reprod. 2010 Nov;83(5):767–73.
21. Amenge J. The prevalence of bacteria in intraamniotic infections in spontaneous labor with intact membranes. University of Nairobi; 2019.
22. Wagura P, Wasunna A, Laving A, Wamalwa D, Ng’ang’a P. Prevalence and factors associated with preterm birth at kenyatta national hospital. BMC Pregnancy and Childbirth. 2018 Apr 19;18(1):107.
23. Mazzulli T. Laboratory Diagnosis of Infection Due to Viruses, Chlamydia, Chlamydophila, and Mycoplasma. In: Long SS, Prober CG, Fischer M, editors. Principles and Practice of Pediatric Infectious Diseases (Fifth Edition) [Internet]. Elsevier; 2018 [cited 2021 Apr 25]. p. 1434-1447.e5. Available from: https://www.sciencedirect.com/science/article/pii/B9780323401814002875
Comments
Post a Comment