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\begin{document}

\title{Gestational period-specific renal functions: Evidence from a large,
community-based, prospective cohort in rural Sri Lanka}



\author[1]{Suneth Agampodi}%
\author[1]{Thilini Agampodi}%
\author[1]{Gayani Amarasinghe}%
\author[1]{Janith Warnasekara}%
\author[1]{Ayesh Hettiarachchi}%
\author[1]{Imasha Jayasinghe}%
\author[2]{Iresha Koralagedara}%
\author[1]{Parami Abeyrathna}%
\author[1]{Shalka Srimantha}%
\author[1]{Nirmani de Silva}%
\author[1]{Nuwan  Darshana Wickramasinghe}%
\affil[1]{Rajarata University of Sri Lanka}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective To estimate the gestational age-specific serum creatinine
(sCr) in pregnancy. Design A population-based prospective cohort study.
Settings Anuradhapura district, Sri Lanka Population or sample Study
group: Healthy pregnant women with a period of gestation less than 12
weeks and without pre-existing medical conditions. Comparison group: A
sample of non-pregnant reproductive age females from a population-based
renal screening. Methods Baseline data were compared among pregnant and
non-pregnant groups and the pregnant women were followed-up until the
end of the second trimester. Main Outcome Measures Gestational
period-specific sCr. Results A total of 2,259 pregnant women and 2.012
non-pregnant women were recruited. The mean (SD) sCr of the 2,012
nonpregnant women was 62.8(12.4) \selectlanguage{greek}μ\selectlanguage{english}mol/L, with the 97.5th percentile of
89.0 \selectlanguage{greek}μ\selectlanguage{english}mol/L. The mean (SD) eGFR was 105.1(27.9) mL/min/1.73 m2. At 4-7,
8-9, 10-12, 24-27 and 28-30 weeks of pregnancy, the mean sCr was 55.1,
52.7, 51.0, 47.2, and 49.3, while the 97.5th percentile for sCr was
72.4, 69.2, 69.3, 63.9, and 66.0 \selectlanguage{greek}μ\selectlanguage{english}mol/L, respectively, in the sample of
pregnant women. In the first and second trimesters, the average sCr
value was 84.7\% and 76.4\% of that of the nonpregnant group,
respectively. The mean eGFR increased up to 129.4 mL/min/1.73 m2 in the
24th week of gestation. The analysis of cohort data clearly confirmed a
significant reduction in sCr with advancing pregnancy (p\textless{}0
.001). Conclusions This study confirms that the precise normative data
needs to be considered in the interpretation of sCr in pregnancy, based
on the period of gestation.%
\end{abstract}%



\sloppy


\textbf{Title:} Gestational period-specific renal functions: Evidence
from a large, community-based, prospective cohort in rural Sri Lanka

\textbf{Authors}

Suneth Buddhika Agampodi. MD\textsuperscript{1}

Thilini Chanchala Agampodi. PhD\textsuperscript{1}

Gayani Shashikala Amarasinghe. MSc. \textsuperscript{1}

Janith Niwanthaka Warnasekara. MPH\textsuperscript{1}

Ayesh Umeshana Hettiarachchi. MBBS\textsuperscript{1}

Imasha Upulini Jayasinghe. MBBS\textsuperscript{1}

Iresha Sandamali Koralegedara. MBBS\textsuperscript{2}

Parami Lakshani Kumari Abeyrathna. MBBS\textsuperscript{3}

Shalka Madushan Srimantha. BSc\textsuperscript{1}

Farika Nirmani de Silva. BSc\textsuperscript{1}

Nuwan Darshana Wickramasinghe. MD\textsuperscript{1}

\textsuperscript{1}Department of Community medicine, Faculty of Medicine
and Allied Sciences, Rajarata University of Sri Lanka.

\textsuperscript{2} Department of Anatomy, Faculty of medicine and
Allied Sciences, Rajarata University of Sri Lanka

\textsuperscript{3}Department of Family Medicine, Faculty of medicine
and Allied Sciences, Rajarata University of Sri Lanka

\textbf{Corresponding author}

Suneth Buddhika Agampodi

Department of Community medicine, Faculty of Medicine and Allied
Sciences, Saliyapura, Sri Lanka 50008

Mobile: +94777880096

\textbf{Source of Support} : This research was supported by the
Accelerating Higher Education Expansion and Development (AHEAD)
Operation of the Ministry of Higher Education, Sri Lanka funded by the
World Bank.

\textbf{Running title:} Renal functions in pregnancy

\textbf{Abstract}

Objective

To estimate the gestational age-specific serum creatinine (sCr) in
pregnancy.

Design

A population-based prospective cohort study.

Settings

Anuradhapura district, Sri Lanka

Population or sample

Study group: Healthy pregnant women with a period of gestation less than
12 weeks and without pre-existing medical conditions. Comparison group:
A sample of non-pregnant reproductive age females from a
population-based renal screening.

Methods

Baseline data were compared among pregnant and non-pregnant groups and
the pregnant women were followed-up until the end of the second
trimester.

Main Outcome Measures

Gestational period-specific sCr.

Results

A total of 2,259 pregnant women and 2.012 non-pregnant women were
recruited. The mean (SD) sCr of the 2,012 nonpregnant women was
62.8(12.4) \selectlanguage{greek}μ\selectlanguage{english}mol/L, with the 97.5th percentile of 89.0 \selectlanguage{greek}μ\selectlanguage{english}mol/L. The mean
(SD) eGFR was 105.1(27.9) mL/min/1.73 m2. At 4-7, 8-9, 10-12, 24-27 and
28-30 weeks of pregnancy, the mean sCr was 55.1, 52.7, 51.0, 47.2, and
49.3, while the 97.5th percentile for sCr was 72.4, 69.2, 69.3, 63.9,
and 66.0 \selectlanguage{greek}μ\selectlanguage{english}mol/L, respectively, in the sample of pregnant women. In the
first and second trimesters, the average sCr value was 84.7\% and 76.4\%
of that of the nonpregnant group, respectively. The mean eGFR increased
up to 129.4 mL/min/1.73 m2 in the 24th week of gestation. The analysis
of cohort data clearly confirmed a significant reduction in sCr with
advancing pregnancy (p\textless{}0 .001).

Conclusions

This study confirms that the precise normative data needs to be
considered in the interpretation of sCr in pregnancy, based on the
period of gestation.

\textbf{Key words} : renal functions, pregnancy, serum creatinine,
threshold,



\textbf{Introduction}

Owing to the alteration of the renin-angiotensin-aldosterone system
(RAAS) and other maternal hormonal changes, systemic vascular resistance
decreases during pregnancy, leading to lower blood pressure and an
increase in renal plasma flow\textsuperscript{1}. Studies using inulin,
paminohippurate clearances\textsuperscript{2} and 24-hour creatinine
clearance\textsuperscript{3} suggest that with augmented blood flow,
renal vasodilatation and volume expansion up to 70\%, a progressive
increase in glomerular filtration occurs during pregnancy. Due to the
rapid and dynamic changes in renal physiology during pregnancy,
assessing renal functions and deciding on thresholds for normal and
abnormal values is a major challenge in clinical practice.

Assessing renal functions in routine obstetric practice is a challenge.
Both cystatin C- and serum creatinine (sCr)-based equations have been
shown to systematically underestimate the glomerular filtration rate
(GFR) in pregnancy \textsuperscript{4-7}. Thus, 24-hour urine collection
remains the standard method for estimating GFR, while sCr is used in
clinical settings as a more feasible test for the assessment of renal
functions in routine practice\textsuperscript{8}. Nevertheless, both
sCr- and sCr-based eGFR were shown to be predictive of adverse outcomes
in pregnancy\textsuperscript{9-11}, although the latter was proven to be
an inaccurate estimate of renal functions in
pregnancy\textsuperscript{12}.

In a recent study using electronic data from 243,534 pregnancies showed
that sCr rapidly decreases from 60 \selectlanguage{greek}μ\selectlanguage{english}mol/L prepregnancy to approximately
47 \selectlanguage{greek}μ\selectlanguage{english}mol/L at 16-32 weeks\textsuperscript{13}. This observations is
consistent with the findings of two recent systematic
reviews\textsuperscript{14, 15}. One review\textsuperscript{14} included
49 studies with 4,421 serum creatine measurements. The authors proposed
85\%, 80\%, and 86\% of the nonpregnant sCr upper limit in sequential
trimesters as the standards for deciding ``abnormal'' values. Another
systematic review\textsuperscript{15} included 29 studies in the
analysis and showed that sCr reduction was most prominent at 15-21 weeks
of gestation, with a 23.2\% reduction, slightly more than the percentage
estimated in the previous systematic review. Both systematic reviews
discussed a number of limitations in published literature including
small samples size, heterogeneous nature of studies, retrospective/
secondary data use and use of sCr values, which were requested based on
clinical grounds.

Against the backdrop of these important evidence gaps, the present study
was designed to assess the renal function of pregnant women using a
population-based prospective cohort design with comparable reference
data drawn from the same reference population without sampling bias.

\textbf{Methods}

Study setting

This study was a component of the Rajarata Pregnancy Cohort
(RaPCo)\textsuperscript{16}. The study was performed in Anuradhapura,
the largest district (geographically) in Sri Lanka. All pregnant women
newly registered from July to September 2019 and residing in
Anuradhapura were invited to participate in RaPCo and it recruited more
than 90\% of newly registered pregnant women in the district.

Out of the total of 3,407 pregnant women recruited for the RaPCo study,
all pregnant women more than 18 years of age with a period of gestation
(PoG) less than 12 weeks at recruitment were included in the present
study. PoG was confirmed retrospectively after the dating ultrasound
scan. The exclusion criteria included pregnant women with uncertain
dates; a history of physician-diagnosed renal diseases, hypertension,
diabetes mellitus, ischaemic heart diseases, hyperlipidaemia, autoimmune
diseases, and thyroid dysfunctions; pregnant women with any renal
disorders, hypertensive disorders and hyperglycaemic conditions in
previous pregnancies and multiple pregnancies. At the baseline
assessment, a 75 g OGTT was performed, and all pregnant women with
fasting plasma glucose greater than 126 mg/dL and 2-hr plasma glucose
greater than 200 mg/dL were excluded. Pregnant women with systolic blood
pressure greater than 140 mmHg and/or diastolic blood pressure greater
than 90 mmHg at the first visit (screened using Omron OMRON HEM-7320)
were also excluded. A follow-up assessment was performed towards the end
of the second trimester. Study participants were invited to participate
in the follow-up clinic at approximately 24-28 weeks of gestation. Only
those who attended the clinics at 24-30 weeks were included in the
follow-up analysis.

A sample of venous blood was collected in a plain tube by a qualified
nursing officer. All collected samples were stored at -80\selectlanguage{ngerman}°C for further
analysis. Serum creatinine was assessed using a creatinine-sarcosine
oxidase method (CREA-S) assay kit in a fully automated Mindray BS-240
clinical chemistry analyser. For the estimation of eGFR, the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used.

A sample of healthy non-pregnant females of reproductive age
participating in a large community-based chronic kidney disease (CKD)
screening programme in Anuradhapura in 2015-16 were recruited as the
comparison group\textsuperscript{17}. To define the age groups
(nonpregnant women) and PoG groups (pregnant women) for the analysis, a
homogenous subset identification table of ANOVA was used. A one-way,
two-way or repeated-measures ANOVA was used as appropriate for the
analysis. The proposed threshold for `abnormal' sCr was based on the
97.5\textsuperscript{th} percentile.

\textbf{Results}

Renal functions of nonpregnant women of reproductive age

Data from 2,012 nonpregnant women of reproductive age were available for
the comparison group. The mean (SD) age of this group was 35.9 (8.2)
years. The mean (SD) sCr of the group was 62.8 (12.4) \selectlanguage{greek}μ\selectlanguage{english}mol/L with a
97.5\textsuperscript{th} percentile of 89.0 \selectlanguage{greek}μ\selectlanguage{english}mol/L. The mean (SD) eGFR
was 105.1 (27.9) mL/min/1.73 m\textsuperscript{2} with a median of 100.8
(IQR 85.5-118.4) mL/min/1.73 m\textsuperscript{2}. The distribution of
sCr and eGFR showed that the sCr values were fairly normally distributed
(skewness of 0.182), while eGFR was skewed to the right (skewness of
1.21). However, the Kolmogorov-Smirnov statistics showed a violation of
normality for both parameters (p\textless{}0.001). Age-disaggregated
mean sCr and eGFR values were compared to identify homogenous subsets of
age groups using one-way ANOVA. Based on the ANOVA results, two
subgroups for sCr and three subgroups for eGFR were identified (Table
1). Although the mean sCr was significantly different, the
95\textsuperscript{th} percentile for sCr was almost similar.

The pregnancy cohort

A total of 2,259 pregnant women were included in this analysis. The mean
(SD) age of the study sample was 28.4 (5.3) years. The numbers of
pregnant women in their first, second and third pregnancies were 508
(22.5\%), 834 (36.9\%) and 619 (27.4\%), respectively. sCr in the
pregnancy cohort was reasonably normally distributed (skewness 0.067)
with a mean (SD) of 53.2 (8.7) \selectlanguage{greek}μ\selectlanguage{english}mol/L. The
97.5\textsuperscript{th}percentile for the SC in the first trimester was
70.9 \selectlanguage{greek}μ\selectlanguage{english}mol/L. The mean (SD) eGFR was 123.4 (10.7) mL/min/1.73
m\textsuperscript{2}, with a median of 123.5 (IQR 118.1-144.0)
mL/min/1.73 m\textsuperscript{2}. During the follow-up at 24-30 weeks of
PoG (992 pregnant women), the mean SC (SD) was 48.0 (8.2) \selectlanguage{greek}μ\selectlanguage{english}mol/L, with a
slightly skewed distribution (skewedness 1.9). The
97.5\textsuperscript{th} percentile for sCr from 24\textsuperscript{-}30
weeks was 65.2 \selectlanguage{greek}μ\selectlanguage{english}mol/L. The mean (SD) eGFR was 127.4 (9.6) mL/min/1.73
m\textsuperscript{2} , with a median of 127.9 (IQR 122.4-133.8)
mL/min/1.73 m\textsuperscript{2}.

From the 4\textsuperscript{th}-5\textsuperscript{th} week of PoG, SC
continued to decrease steadily until the completion of 12 weeks (Figure
1). At the 24\textsuperscript{th} week, a further decline in sCr was
observed, and it started to increase after the
25\textsuperscript{th}week. The respective eGFR values followed the
inverse pattern, with the highest value at approximately the
24\textsuperscript{th} week. Homogenous subsets of sCr values according
to PoG were prepared for further analysis using one-way ANOVA (Table 2).
In these groups, a one-way between-group ANOVA was conducted to explore
the impact of PoG on sCr. There was a significant difference in sCr for
the three groups {[}F (4,3250)=95.703, p\textless{}0.001{]}. The effect
size calculated using eta squared was 0.105 (medium to large effect).
Post hoc comparisons using Tukey's HSD test indicated that the mean sCr
for each PoG group was significantly different from that of other
adjacent groups.

As age showed an effect on sCr in the nonpregnant cohort, the values of
the pregnancy cohort were further analysed according to age categories.
After the initial descriptive analysis and subset analysis, participants
were divided into two groups according to their age (Group 1: less than
35 years; Group 2: 35 years and above). Using a two-way ANOVA for age
and PoG, the interaction effect between PoG and age group was found to
be marginal {[}F(4,3251)=2.331, p=0.054{]}. There was a statistically
significant main effect for PoG {[}F(4,3251)=45.112,
p\textless{}0.001{]}, and the effect size was small to medium (partial
eta squared=0.052). Post hoc comparisons using Tukey's HSD test
indicated that even after including age in the model, the mean sCr for
each PoG group was significantly different from that of the adjacent
groups. The main effect of age {[}F(1,3251)=5.760, p=0.016{]} was also
significantly different across age groups, with a small effect and
higher sCr for the age group of 35 years and above.

To further assess the changes in renal functions using the cohort
design, a one-way repeated-measures ANOVA was conducted. This analysis
was conducted only for those who had follow-up data at 24-27 weeks of
PoG, in which the lowest sCr was observed (n=524). Three groups were
defined according to the PoG at the time of recruitment as above. The
mean (SD) values of the first and second measures are presented in Table
3. There was a significant reduction in sCr with advancing pregnancy
{[}Wilks' Lambda=0.71, F(1,521)=211.202, p\textless{}0.001, multivariate
partial eta squared=0.288{]}. This analysis showed that despite having
different mean values based on the PoG, at 24-27 weeks, the PoG values
were concentrated around a mean value of 47 \selectlanguage{greek}μ\selectlanguage{english}mol/L.

\textbf{Discussion}

In this prospective cohort study, we systematically recruited a
population-based sample of women with singleton pregnancies, excluding
all comorbidities, to generate proper ``normality data'' for sCr in
pregnancy. This prospective study, probably one of the largest reported
so far for the first trimester renal function assessment in pregnancy
with 2,259 pregnant women and with 992 follow-ups, provides evidence to
confirm the previous observation and to enhance the precision estimates
probably valid across the South Asian region.

Different upper normal limits for sCr have been proposed without
consensus for many years. The suggested values varied, with different
studies reporting 72 \selectlanguage{greek}μ\selectlanguage{english}mol/L\textsuperscript{18}, 89
\selectlanguage{greek}μ\selectlanguage{english}mol/L\textsuperscript{19}, 80 \selectlanguage{greek}μ\selectlanguage{english}mol/L\textsuperscript{20} and 95
\selectlanguage{greek}μ\selectlanguage{english}mol/L\textsuperscript{21} as upper limits. A similar study performed
recently in China also published higher upper values of 68, 66, and 68
\selectlanguage{greek}μ\selectlanguage{english}mol/L for the first, second, and third trimesters,
respectively\textsuperscript{22}. In 2019, the Renal Association
comprehensively reviewed the published guidelines from the National
Institute of Health and Care Excellence (NICE), UK Consensus Group on
Pregnancy in Renal Disease, and Kidney Disease Outcomes Quality
Initiative (KDOQI) and searched Ovid Medline (1946 to 2018) for
``Clinical practice guideline on pregnancy and renal
disease''\textsuperscript{8}. This guideline used the two most recent
reviews: the Canadian study\textsuperscript{13} and the systematic
review published in 2019. In comparison with the
95\textsuperscript{th}percentile reported in the Canadian study, the
95\textsuperscript{th}percentiles observed in our study cohort in the
first and second trimesters were slightly higher. In weeks 4-7, 8-9,
10-12, 24-27 and 28-30, a previous study reported 70, 65, 61, 59 and 59
\selectlanguage{greek}μ\selectlanguage{english}mol/L, respectively, as the 95\textsuperscript{th} percentile, while
our study reported 69.5, 66.7, 65.4, 59.6 and 63.4 \selectlanguage{greek}μ\selectlanguage{english}mol/L, respectively.
Compared with the systematic review, which reported 85\% and 80\% of
prepregnancy sCr values in the first and second trimesters, we observed
values of 84.7\% and 76.4\% compared with the nonpregnant group,
respectively, showing a slightly higher decrease at the end of the
second trimester. In our study, we tried to overcome the listed
limitations in both studies by using a prospective design and including
all ``healthy pregnant women''.

Sri Lanka is a country with an ongoing epidemic of chronic kidney
disease of unknown origin (CKDu)\textsuperscript{23, 24}. Anuradhapura,
where the present study was performed, is one of the most affected
districts\textsuperscript{25}. A previous study performed in the same
study area among pregnant women showed a mean eGFR of 145.5 mL/min/1.73
m\textsuperscript{2} \textsuperscript{26}, which is higher than the
numbers presented in the present study (122-130 mL/min/1.73
m\textsuperscript{2}). That particular study was not conducted
specifically among healthy pregnant women; thus, the eGFR estimates may
be slightly different. In the same study area, early renal damage among
children was proposed\textsuperscript{27}, raising the question of
whether CKDu is partly due to an early enviormental impact. Based on
these observations, a higher prevalence of renal problems might be
expected even among pregnant women showing high mean sCr values.
Nevertheless, the use of the nonpregnant comparison group and
application of percentage increase will overcome this issue when
generalizing the results.

CKD-EPI was used in this study to estimate the eGFR. While this formula
has been shown to underestimate eGFR during
pregnancy\textsuperscript{28}, CKD-EPI has good performance postpartum
and outside pregnancy, and the current evidence does not suggest that a
superior formula is available for eGFR estimation in
pregnancy\textsuperscript{29}.

To strengthen the observations and to evaluate the utility of the
proposed normality data, a long follow-up of the same cohort is required
with proper assessment of maternal and foetal outcomes. Although the
sCr-based eGFR is not an accurate estimate during pregnancy, previous
studies have shown that it could be used as a predictor of adverse
pregnancy outcomes\textsuperscript{9, 10}. As the normality data
generated through this study are almost similar to the values observed
in the previous secondary data analysis, these values seem universally
valid across geographical regions \textsuperscript{13}.

\textbf{Conclusions}

This prospective cohort study confirms the previous observations on
changes in sCr values in pregnancy with thresholds for normal and
abnormal values almost similar to those observed in completely different
geographical and ethnic settings. The rapid decrease in early pregnancy
sCr and differences across trimesters need to be taken into account
during clinical practice while interpreting sCr in pregnancy. Extension
of prospective studies from early pregnancy to late infancy will provide
confirmatory data on the upper threshold values for sCr as a biomarker
of adverse pregnancy outcomes.

\textbf{Acknowledgment}

We acknowledge the north central province and Anuradhapura district
public health staff for the support given during this study.

\textbf{Disclosure statement}

We received grant from Accelerating Higher Education Expansion and
Development (AHEAD) Operation of the Ministry of Higher Education, Sri
Lanka for this work.

\textbf{Contribution to Authorship}

SBA conceptualized the study, analysed and interpreted data and prepared
the initial draft of the manuscript. SBA, TCA and NDW design the study.
GSA, JNW, AUH, IUJ, ISK and PLKA participated in planning field work,
data collection including clinical assessments and examinations. SMS and
FNS involved in planning the biochemical assessments, sample collection,
laboratory procedures and revising the relevant components in the
manuscript. All authors approved the final version of the manuscript.
All authors have agreed to be accountable for the authors own
contributions and to ensure questions related to the accuracy or
integrity of any part of the work are appropriately investigated,
resolved, and the resolution documented in the literature.

\textbf{Ethics approval}

Ethical clearance for the RaPCo study was obtained from the ethics
review committee of the Faculty of Medicine and Allied Sciences,
Rajarata University of Sri Lanka (ERC/2019/07).

\textbf{Funding}

This research was supported by the Accelerating Higher Education
Expansion and Development (AHEAD) Operation of the Ministry of Higher
Education, Sri Lanka funded by the World Bank. The funding agency has no
role in the design of the study and collection, analysis, and
interpretation of data and in writing the manuscript.

\textbf{Disclosure of interests}

We have no conflict of interests to declare.

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\textbf{Figure and table legends}

\textbf{Table 1.} Distribution of serum creatinine and eGFR values by
age among nonpregnant females of reproductive age in North Central
Province, Sri Lanka

\textbf{Table 2.} Distribution of serum creatinine and eGFR by period of
gestation (grouped) in 2,259 pregnant women during the first trimester
and follow-up in Anuradhapura, Sri Lanka

\textbf{Table 3.} Results of paired sample serum creatinine among 524
pregnant women with follow-up measurements performed between 24-27 weeks

\textbf{Figure 1.} Distribution of serum creatinine and eGFR by the
period of gestation in 2,259 pregnant women during the first trimester
and follow-up at 24-30 weeks

\textbf{Table 1.} Distribution of serum creatinine and eGFR values by
age among nonpregnant females of reproductive age in North Central
Province, Sri Lanka\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\textbf{Age (years)} & \textbf{N} & \textbf{Mean} & \textbf{Std.
Deviation} & \textbf{Std. Error} & \textbf{97.5\textsuperscript{th}
Percentile}\tabularnewline
\midrule
\endhead
\textbf{Serum creatinine} (\selectlanguage{greek}μ\selectlanguage{english}mol/L) & \textbf{Serum creatinine} (\selectlanguage{greek}μ\selectlanguage{english}mol/L)
& & & &\tabularnewline
\textless{}35 & 920 & 60.93 & 12.383 & 0.408 & 88.6\tabularnewline
35 and above & 1,092 & 64.45 & 12.222 & 0.370 & 89.2\tabularnewline
\textbf{eGFR} (mL/min/1.73 m\textsuperscript{2}) & \textbf{eGFR}
(mL/min/1.73 m\textsuperscript{2}) & \textbf{eGFR} (mL/min/1.73
m\textsuperscript{2}) & & &\tabularnewline
\textless{}30 & 534 & 118.7 & 30.533 & 1.321 &\tabularnewline
30-34 & 386 & 107.19 & 25.624 & 1.304 &\tabularnewline
35 and above & 1,092 & 97.72 & 24.418 & 0.739 &\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2.} Distribution of serum creatinine and eGFR by period of
gestation (grouped) in 2,259 pregnant women during the first trimester
and follow-up in Anuradhapura, Sri Lanka\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\textbf{PoG (Weeks)} & \textbf{N} & \selectlanguage{greek}\textbf{Serum creatinine μmol/L} &
\selectlanguage{greek}\textbf{Serum creatinine μmol/L} & \textbf{95\% CI for Mean} &
\textbf{95\% CI for Mean} & \textbf{97.5\textsuperscript{th} Percentile}
& \textbf{eGFR} & \textbf{eGFR}\tabularnewline
\midrule
\endhead
& & \textbf{Mean} & \textbf{SD} & \textbf{Lower} & \textbf{Upper} & &
\textbf{Mean} & \textbf{SD}\tabularnewline
4-7 & 830 & 55.1 & 8.5 & 54.5 & 55.7 & 72.4 & 122.0 &
10.9\tabularnewline
8-9 & 871 & 52.7 & 8.3 & 52.2 & 53.3 & 69.2 & 123.7 &
10.4\tabularnewline
10-12 & 558 & 51.0 & 8.9 & 50.3 & 51.7 & 69.3 & 125.0 &
10.7\tabularnewline
24-27 & 708 & 47.2 & 7.3 & 46.6 & 47.7 & 63.9 & 129.4 &
9.2\tabularnewline
28-30 & 284 & 49.3 & 9.9 & 48.1 & 50.5 & 66.0 & 127.6 &
11.7\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3.} Results of paired sample serum creatinine among 524
pregnant women with follow-up measurements performed between 24-27 weeks\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
& & \selectlanguage{greek}\textbf{Serum creatinine μmol/L}\selectlanguage{english} & \selectlanguage{greek}\textbf{Serum creatinine μmol/L}\selectlanguage{english}
& \selectlanguage{greek}\textbf{Serum creatinine μmol/L}\selectlanguage{english} & \selectlanguage{greek}\textbf{Serum creatinine
μmol/L}\selectlanguage{english}\tabularnewline
\midrule
\endhead
& & \textbf{1\textsuperscript{st} trimester (4-12 weeks)} &
\textbf{1\textsuperscript{st} trimester (4-12 weeks)} & \textbf{End of
2\textsuperscript{nd} trimester (24-27\textsuperscript{th} weeks)} &
\textbf{End of 2\textsuperscript{nd} trimester
(24-27\textsuperscript{th} weeks)}\tabularnewline
\textbf{PoG at the first visit} & \textbf{N} & \textbf{Mean} &
\textbf{SD} & \textbf{Mean} & \textbf{SD}\tabularnewline
4-7 weeks & 150 & 54.4 & 8.7 & 47.2 & 8.1\tabularnewline
8-9 weeks & 238 & 52.8 & 8.6 & 47.5 & 7.3\tabularnewline
10-12 weeks & 136 & 49.6 & 8.9 & 47.0 & 6.9\tabularnewline
Total & 524 & 52.4 & 8.9 & 47.3 & 7.4\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig3/Fig3}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

