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ORIGINAL ARTICLE
Year : 2023 | Volume
: 30
| Issue : 1 | Page : 25-30
Microalbuminuria and its association with adverse pregnancy outcome in a tertiary health centre in Nigeria
Khadijat Omodunni Afolabi-Oboirien1, Abubakar Abubakar Panti2, Karima Abubakar Tunau2, Aaron Eze Ukwu2, Muhammad Bashir Abdulrahman3, Jamila Abubakar Garba4
1 Department of Obstetrics and Gynaecology, Dalhatu Araf Specialist Hospital, Lafia, Nasarawa, Nigeria
2 Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
3 Department of Chemical Pathology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
4 Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
Correspondence Address:
Abubakar Abubakar Panti
Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto
Nigeria
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/npmj.npmj_293_22
Background: Adverse pregnancy outcomes occur more commonly in developing countries and are still prevalent in our sub-region. Microalbuminuria is a marker of endothelial dysfunction and has been proposed as an aetiological factor in the development of some adverse pregnancy outcomes such as pre-eclampsia, intrauterine growth restriction (IUGR) and pre-term labour. Aim: The aim is to determine the prevalence of microalbuminuria and its association with adverse pregnancy outcomes. Methods: This was a prospective cross-sectional study with follow-up amongst women in early pregnancy presenting at Usmanu Danfodiyo University Teaching Hospital, Sokoto. Three hundred and thirty women with singleton pregnancy at gestational age <20 weeks, blood pressure <140/90 mmHg, normal fasting blood sugar and normal renal function were recruited. Those with a history of hypertension, diabetes mellitus, chronic kidney disease, sickle cell anaemia were excluded, multiple pregnancies, urinary tract infection or positive dipstick proteinuria at first contact were excluded. They were recruited consecutively and a structured interviewer-administered questionnaire was completed. Single-spot urine analysis for albumin was performed. The women were followed up to the time of delivery and the puerperium and any adverse outcome were documented. Results: The prevalence of microalbuminuria was 58.4%. The maternal and foetal adverse outcomes such as hypertensive disorders of pregnancy, pre-mature rupture of membrane, IUGR, preterm birth and stillbirth occurred more amongst the women with microalbuminuria. However, there was no statistically significant association between microalbuminuria and having these adverse outcomes (P > 0.05). Conclusion: There was a high prevalence of microalbuminuria amongst healthy pregnant women and pregnancy complications occurred more frequently in women with microalbuminuria than in those without. However, this association was not sufficient to predict adverse outcomes in pregnancy.
Keywords: Adverse pregnancy outcome, foetal, maternal, microalbuminuria
Pregnancy is one of the most important events in the life of any family. Any cause of adverse outcomes during this period is a cause for concern. Adverse events such as pre-eclampsia, pre-term labour, pre-term pre-mature rupture of membranes (PROMs), intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM) are possible complications of pregnancy that have a significant impact on both maternal and foetal well-being.[1] It is, therefore, important to evaluate the predictors of these adverse outcomes before their onset and institute management early to prevent these complications.
The term 'microalbuminuria' is a relative misnomer: It suggests 'small size', but it means the presence of a ‘small quantity of protein’ in the urine[2] This term was used first about 30 years ago by Viberti et al.[2] It means an abnormally high excretion rate of albumin in the urine within the range of 30–299 mg/g creatinine.[3] This is below the sensitivity of conventional semi-quantitative test strips.[4] Microalbuminuria is said to occur when albumin is increased within the normal range of albumin in the urine.
In the general population, microalbuminuria is associated with obesity, hypertension, diabetes mellitus and subclinical renal disease.[5],[6] Microalbuminuria is a sign of endothelial dysfunction and implies a higher likelihood for the development of cardiovascular morbidity and mortality, particularly in high-risk populations such as those with diabetes mellitus and hypertension.[3] It has also been suggested that microalbuminuria occurs a few weeks before the appearance of overt proteinuria and is a probable predictor of pre-eclampsia.[7] Vascular endothelial dysfunction was proposed to be an aetiology of IUGR, pre-eclampsia and pre-term labour.[8]
So far, attempts at using microalbuminuria as a predictor of pre-eclampsia have yielded variable results.[9] In South America, Conde-Agudelo et al.[10] found that the sensitivity of microalbuminuria for the prediction of pre-eclampsia was 7%–90% and the specificity of 29%–97%; which is of low value in clinical practice.[10] In Bangladesh, the sensitivity of albumin-to- creatinine ratio (ACR) for the prediction of pre-eclampsia is 80%, specificity of 49.54% and positive and negative predictive values of 12.69% and 96.42%, respectively.[9] In Nigeria, a similar sensitivity and specificity (88.9% and 67.9%) were recorded, but the positive and negative predictive values were 22.2% and 98.3%, respectively.[11]
Current guidelines use urinary ACR in conjunction with an estimated glomerular filtration rate (GFR) to stage chronic kidney disease.[12] The urinary ACR is a well-validated tool in the diagnosis and prognosis of kidney disease outside pregnancy.[12] It has been reported that healthy pregnant women may excrete albumin in amounts not detectable by conventional dipstick tests[4] and that microalbuminuria determination using ACR is a fast, inexpensive and simple way of detecting urinary albumin excretion. It is therefore important to carry out research that will detect the presence of microalbumin in the urine of healthy pregnant women. In addition, there is also the need to evaluate the effectiveness of microalbuminuria measurement in determining adverse pregnancy outcomes. One of such adverse pregnancy outcomes is preeclampsia/eclampsia, which is a leading cause of maternal and perinatal morbidity and mortality in Sokoto.[13] This may help in identifying women at risk to intensify maternal as well as foetal surveillance to improve the outcome of the pregnancy. There are also limited studies on the prevalence of microalbuminuria amongst pregnant women and the effect of microalbuminuria on pregnancy outcomes in Nigeria. This study aimed at determining the prevalence of microalbuminuria and its association with adverse pregnancy outcomes. The information generated in this study may be useful in the management of pregnant women by improving pregnancy outcomes and making it a fulfilling experience for them and their families.
MethodsEthics
The study was conducted in compliance with the Helsinki Declaration of 1975, and ethical clearance was obtained from Usmanu Danfodiyo University Teaching Hospital (UDUTH) Health Research and Ethics Committee, Sokoto, Sokoto State. It was obtained on 1st June 2017 with reference number HREC/2017/No. 586. In addition, written and informed consent was obtained from the respondents before data collection. The duration of the study was from July 2017 to February 2018.
Study design
This was a prospective cross-sectional study with follow-up conducted amongst pregnant women at the antenatal care clinic of UDUTH, Sokoto. The inclusion criteria were women with singleton pregnancy at gestational age <20 weeks estimated by the last menstrual period or ultrasound scan estimation in the first trimester. They were also women with blood pressure <140/90 mmHg, normal fasting blood sugar and normal renal function. Those with a history of hypertension, diabetes mellitus, chronic kidney disease or sickle cell anaemia were excluded from the study. Those with multiple pregnancies, symptoms of UTI or positive dipstick proteinuria at first contact were also excluded from the study.
Sample size determination
The sample size was determined for each of the study objectives and the prevalence formula[14] for the objective of determining of prevalence of microalbiminuria was the highest; hence, it was used for the study.
The sample size was calculated using the formula: n = Z2pq/d2
where: n = Sample size
Z2 = Standard normal deviation at 95% confidence interval = 1.96
P = Prevalence of microalbuminuria from a previous study (23.7%)[11]
q = Complementary probability of P (q = p-1) = 0.82
d = 5%= 0.05
Assuming a precision within plus or minus 5% (desired precision, d = 0.05) and also a 95% confidence interval assuming that 95% of the time, the sample estimates will fall within 1.96 standard errors of the specified population value, if it were the true value.
To accommodate for attrition, the estimated sample size, n, was divided by 0.9 (with the anticipation of a 90% response rate, R). Thus, ns = n/R = 277/0.9 = 308 subjects.
However, a total of 330 women were recruited to improve the power of the study.
Study protocol
The pregnant women attending the antenatal clinic of UDUTH who met the inclusion criteria and consented to participate in the study were recruited consecutively till the desired sample size was achieved. The duration of the study was from July 2017 to February 2018.
At first contact, a detailed history was taken with emphasis on parity, last menstrual period (to ascertain the gestational age) and to ensure that the inclusion criteria and exclusion criteria have been met. Those with symptoms of UTI were excluded from the study. Blood was drawn using a vacuum extraction system into a plain vacutainer glass bottle and a fluoride oxalate vacutainer bottle to assess for urea and creatinine and blood sugar, respectively. This was done to exclude chronic kidney disease and diabetes mellitus. Then, the respondents were requested to give a mid-stream, clean-catch urine sample to screen for proteinuria (which possibly implies the presence of an ongoing UTI) and to assess the specific gravity of the urine. This was to ensure that those with positive dipstick proteinuria were excluded and that the sample given was urine.
The urine albumin (mg/L) was determined by immunoturbidimetry. During the analysis of samples, any urine specimen that was turbid or contained particles or was positive for blood and or protein on the dipstick was discarded and another sample was taken at a later date as long as the client was within gestational age for inclusion in the study. The urine sample of any client with blood sugar level ≥5.1 mmol/L and creatinine levels >1.2 mg/dL was not analysed.
All the women received routine antenatal care and were followed till delivery and puerperium for the development of adverse pregnancy outcomes such as pre-eclampsia/eclampsia, PROMs, pre-term birth and GDM. The end-point of the study was between 28 weeks gestation and the puerperium. Rescue stickers were tagged on the folder of the patient for identification and easy follow-up.
The fetuses were also assessed for IUGR before admission into the neonatal intensive care unit. Pre-eclampsia was defined as elevated blood pressure of 140/90 mmHg or more measured on at least two occasions, between 6 and 8 h apart and significant proteinuria (2+ on dipstick). Pregnancy-induced hypertension was defined as elevated blood pressure without proteinuria. Pre-term birth was defined as labour and delivery before 37 weeks of gestation. PROMs were defined as rupture of membranes before the onset of labour at ≥28 weeks gestational age. IUGR refers to a weight at birth of <2500 g for a term pregnancy. For pre-term pregnancy, IUGR was defined as weight at birth below the 10th percentile for that gestation.
The urine sample from participants (5 mL) was obtained using a clean container and stored at −20°C immediately after collection. The analysis was performed on pooled samples of 45 women. The urine albumin concentration was determined using immunoturbidimetry in mg/L. The urine creatinine concentration was also measured in mg/dL using the modified Jaffe reaction. The reagent for assessment of albumin concentration was MICROALBUMIN (IT) (AGAPPE DIAGNOSTICS) code No: 51824001, 51824002. The detection limit was between 4 mg/L and 395 mg/L.
Microalbuminuria is said to occur when albumin is increased within the normal range of albumin in the urine of 30–299 mg/g creatinine.
Adverse pregnancy outcomes considered in this pregnancy were pre-eclampsia, PROMs, pre-term birth, IUGR and maternal and foetal death.
Statistics
Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 25 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). Maternal history, biophysical measurements and laboratory results were summarised using tables, charts and graphs as appropriate. Continuous variables were presented as mean (±standard deviation) and compared using Student's t-test. Categorical variables were presented as percentages. The Chi-square test was used to determine the association between microalbiminuria and adverse pregnancy outcomes. A value of P < 0.05 was considered statistically significant.
ResultsA total of 330 women were recruited for this study. Of these, 293 (88.8%) women were followed up to the time of delivery and the puerperium. Of the remaining, 5 had a spontaneous miscarriage, 10 relocated and delivered elsewhere and 22 had home delivery. Therefore, the obstetric outcome for these women could not be determined and analysed. Fourteen women had macroalbuminuria (ACR ≥300 mg/g), so they were excluded from the outcome analysis.
The age of the respondents ranged between 16 and 44 years, with a mean of 25.84 ± 5.21 years. The majority of the mothers, 213 (72.7%), were Hausa/Fulani and more than half, 179 (61.1%) of them, were homemakers. The most practiced religion was Islam 250 (85.3%), while 43 (14.7%) were Christians. The majority of the women, 216 (73.7%), had at least secondary education and all the respondents were married. Less than half (46.8%) were in the low socio-economic class [Table 1].
More than half of the women (58.4%) in this study had microalbuminuria (30–299 mg/g) and a minority (4.8%) had macroalbuminuria [Figure 1].
During the period of study, 40 (14.3%) women developed hypertensive disorders of pregnancy (Pregnancy induced hypertension, pre-eclampsia and eclampsia), 16 (5.7%) had PROMs and 4 (1.4%) had abruptio placentae.
The percentage of women who developed an adverse outcome in pregnancy was observed to be higher in the group with microalbuminuria. However, this observation was not statistically significant [Table 2].
Table 2: Association between microalbuminuria and adverse maternal outcome (n=279)The foetal adverse outcomes observed in this study were pre-term birth (5.7%), IUGR (8.2%) and stillbirth (3.6%). Foetal adverse outcomes occurred more amongst the women with microalbuminuria. However, this observation was not statistically significant [Table 3].
Table 3: Association between microalbuminuria and adverse foetal outcome (n=279) Discussion Two hundred and ninety-three women were followed up to the time of delivery and the puerperium in this prospective study. More than half of the women (58.4%) in this study had microalbuminuria. The maternal and foetal adverse pregnancy outcomes were observed to be more amongst those with microalbuminuria, but the difference between those without microalbuminuria was not statistically significant.
The prevalence of microalbuminuria in this study was higher than the findings from previous studies, with a reported prevalence of 7.8%, 18.5%, 22.9% and 23.7%.[11],[15],[16],[17] The prevalence found in this study was about twice the finding by Salako et al. in Ibadan.[11] This is probably because albumin excretion was assessed using the 24-h collection by the researchers in Ibadan, and the sensitivity of albuminuria testing in the present study was improved by using spot urine to determine the ACR. In addition, the reference value used in this work was higher than that used by Bahasadri et al.[1] Another possible reason for the high prevalence of microalbuminuria in this study is that microalbuminuria is twice as high in sub-Saharan Africans because of a higher GFR and a higher risk of developing chronic renal disease.[18] The high prevalence of microalbiminuria may be a pointer to the risk of chronic kidney disease. There is a need for further follow-up and evaluation to ascertain kidney functions.
Amongst the women who developed hypertensive disorders of pregnancy, 60% of them had microalbuminuria, but this association was not statistically significant. This finding was similar to the report by Konstantin et al.[18] who did not find any significant difference in the ACR of women who developed pre-eclampsia and those unaffected. In another study by Singh et al., more women with microalbuminuria developed pre-eclampsia, but this association was not statistically significant.[19] These observations were different from what was reported by Poon et al. in the UK, who found a significant association between microalbuminuria and pre-eclampsia. The difference in this work was probably because a greater proportion of women in this study (68.4%) were in the second trimester, unlike the work done by Poon et al.[20] where all the study participants were in the first trimester and GFR increases with increasing gestational age.
Bahasadri et al.[1] found a significant association between pre-term birth and microalbuminuria. Sobh et al. in Cairo also found a significant association between having microalbuminuria and pre-term birth (P < 0.001).[16] However, women in both studies (Iran and Cairo) were recruited between 24 and 28 weeks when some of the patients had already developed hypertensive disorders of pregnancy which increased the risk for iatrogenic pre-term delivery. In addition, the prevalence of microalbuminuria in this study was high and this may explain the reason why no statistically significant relationship was found between pre-term delivery and microalbuminuria. However, the prevalence of pre-mature rupture of the membrane was found to be higher in women with microalbuminuria. This observation was not statistically significant. Singh et al. also found that there was no association between premature rupture of membranes and microalbuminuria.[19]
Some of the limitations of this study are that it was a single-centre study and the finding may not be generalised. The relatively small sample size may be the reason for finding a non-significant association in adverse pregnancy outcomes between those with microalbuminuria and those without.
ConclusionThe prevalence of microalbuminuria was high amongst women attending antenatal care clinics in UDUTH, Sokoto and maternal and foetal adverse outcomes occurred more amongst women with microalbuminuria. However, this association was not statistically significant. Employing this test as a screening tool in predicting adverse pregnancy outcomes should be interpreted with caution. Other factors may be responsible for these outcomes.
Recommendations
The ability to predict adverse pregnancy outcomes using microalbuminuria was not validated in this study. Nevertheless, it may be prudent to improve surveillance of women with microalbuminuria early in pregnancy. In addition, a population-based study may be necessary to determine the significance of microalbuminuria in pregnancy and this may also be extended to non-pregnant women. Another research using an early morning urine sample for analysis, as advocated by the American Diabetic Association, is suggested.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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