LAPORAN PRESENTASI JURNAL

POSNATAL GESTATIONAL AGE ESTIMATION VIA NEWBORN

SCREENING ANALYSIS: APPLICATION AND POTENTIAL

OLEH……:
KEKOMPOK 3
MOH. HAKIM SETYA NEGARA
2002013012

FAKULTAS ILMU KESEHATAN

PROGRAM STUDI ILMU KEPERAWATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2021
 ANALISIS JURNAL

POSNATAL GESTATIONAL AGE ESTIMATION VIA NEWBORN

SCREENING ANALYSIS: APPLICATION AND POTENTIAL

Oleh:
Kelompok 3
Moh. Hakim Setya Negara
2002013012

Telah Di ACC :
Hari:…………..
Tanggal:………
Dan di nyatakan layak oleh:

Fasilitator

(Tri Lestari Handayani, S.Kep, M.Kep,.Sp.Mat)

 DAFTAR ISI
HALAMAN PENGESAHAN...........................................................................................i
DAFTAR ISI.....................................................................................................................ii
KATA PENGANTAR.....................................................................................................iii
BAB I PENDAHULUAN..................................................................................................1
1.1 Latar Belakang..................................................................................................................1
1.2 Tujuan Penulis..................................................................................................................1
BAB II................................................................................................................................2
LAMPIRAN JURNAL.....................................................................................................2
BAB III PEMBAHASAN...............................................................................................10
3.1 Profile Penelitian............................................................................................................10
3.2 Deskripsi Penelitian berdasarkan metode PICO :..........................................................11
BAB IV PENUTUP.....................................................................................................13
4.1 Kesimpulan.....................................................................................................................13
4.2 Saran...............................................................................................................................13
DAFTAR PUSTAKA.............................................................................................................14
LAMPIRAN 1..............................................................................................................16
LAMPIRAN 2..............................................................................................................16

KATA PENGANTAR

ii
 Dengan memanjatkan puji dan syukur pada kehadirat Allah Subhanahu Wa Ta’ala,
sehingga melalui rahmat-Nya lah penulis dapat menyelesaikan tugas dan laporan analisis
jurnal ini yang berjudul “Postnatal gestational age estimation via newborn screening
analysis: application and potential”

Jurnal ini diajukan untuk memenuhi tugas mata kuliah pada keperawatan maternitas ,
Selama penulisan jurnal ini, penulis banyak mendapatkan dukungan dari berbagai pihak. Oleh
karena itu, penulis menyampaikan banyak ucapan terima kasih kepada semua pihak yang
telah membantu dan mendukung dalam penyelesaian analisis jurnal ini dan terimakasih saya
ucapkan kepada Ibu Tri Lestari Handayani, S.Kep, M.Kep,.Sp.Mat selaku fasilitator
kelompok 3

Penulis menyadari bahwa dalam penyusunan laporan analisis jurnal ini masih banyak
kekurangan. Semoga laporan analisis jurnal kami dapat memberikan manfaat khususnya bagi
penulis dan para pembacanya yang senantiasa tidak pernah putus dalam mengembangkan
ilmu pengetahuan khususnya dibidang kesehatan untuk menambah wawasan.

Malang, 13 oktober 2021

Penulis

iii
 BAB I
PENDAHULUAN

1.2 Latar Belakang

Kehamilan adalah pertumbuhan dan perkembangan janin intra uteri mulai sejak
konsepsi dan berakhir sampai permulaan persalinan. Kehamilan, persalinan, nifas, bayi
baru lahir dan pemilihan alat kontrasepsi merupakan proses fisiologis dan
berkesinambungan. (Marmi, 2011:11). Dan tidak bisa di pungkiri bahwa masa kehamilan,
persalinan, masa nifas, bayi baru lahir hingga penggunaan kontrasepsi, wanita akan
mengalami berbagai masalah kesehatan. Agar kehamilan, persalinan serta masa nifas
seorang ibu berjalan normal, ibu membutuhkan pelayanan kesehatan yang baik. Untuk
peraturan pemerintahan Nomor 61 Tahun 2014 tentang kesehatan reproduksi menyatakan
bahwa setiap perempuan berhak mendapatkan pelayanan kesehatan untuk mencapai
hidup sehat dan mampu melahirkan generasi yang sehat dan berkualitas serta mengurangi
Angka Kematian Ibu (Bandiyah, 2009). Pelayanan kesehatan tersebut sangat dibutuhkan
selama periode ini. Karena pelayanan asuhan kebidanan yang bersifat berkelanjutan
(continuity of care) saat di memang sangat penting untuk ibu. Dan dengan asuhan
kebidanan tersebut tenaga kesehatan seperti bidan, dapat memantau dan memastikan
kondisi ibu dari masa kehamilan, bersalin, serta sampai masa nifas.

Kelahiran prematur merupakan masalah kesehatan global yang utama, berkontribusi

terhadap 35% dari semua kematian neonatus pada tahun 2016. Mengingat pentingnya
memastikan perkiraan kelahiran prematur secara akurat dan dalam Mengingat
keterbatasan saat ini dalam estimasi usia kehamilan postnatal (GA), metode baru untuk
memperkirakan GA postnatal tanpa adanya USG prenatal diperlukan. Pekerjaan
sebelumnya telah menunjukkan potensi metabolomik untuk memperkirakan GA dengan
menganalisis data yang diambil melalui skrining bayi baru lahir rutin.

1.2 Tujuan Penulis

1. Memaparkan informasi terkini dengan evidence based di era keperawatan terkait

dengan topik tertentu
2. Memberikan penjelasan tentang temuan terbaru atau inovasi di dunia keperawatan
3. Meningkatkan critical thinking tentang manfaat hasil penelitian tersebut bagi
dunia keperawatan
 BAB II
LAMPIRAN JURNAL

EXPERT REVIEW OF PROTEOMICS

2019, VOL. 16, NO. 9, 727–731
https://doi.org/10.1080/14789450.2019.1654863

SPECIAL REPORT

Postnatal gestational age estimation via newborn screening analysis:

application and potential
Lindsay A. Wilson a, Malia SQ. Murphya, Robin Ducharmea, Kathryn Denizeb, Nafisa M. Jadavjia, Beth
Potterc,
Julian Littlec, Pranesh Chakrabortyb, Steven Hawken a and Kumanan Wilsona
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; bNewborn Screening Ontario,
a

Children’s Hospital of Eastern

Ontario, Ottawa, Canada; cDepartment of Epidemiology and Community Health, University of Ottawa, Ottawa, Canada

ABSTRACT ARTICLE
Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in HISTORY
2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current Received 12
limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the June 2019
absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for
metabolomics to estimate GA by analyzing data captured through routine newborn screening. Accepted 6
Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn August 2019
screening and demographic data, our group developed an algorithm capable of estimating GA postnatally KEYWORDS
to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by Gestational
including additional analytes and validating the model’s performance through internal and external age;
validation studies, and through implementation of the model internationally.
Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but
is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus
on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible
and acceptable to individuals in low-resource settings.

metabolomics; newborn screening

1. Introduction from 8.7% in Europe to 13.4% in North Africa [3].

However, there is uncertainty as to the accuracy
Preterm birth, defined as birth that occurs before
of these estimates in low- and middle-income
37 weeks’ gestation, is a major public health
settings due to the limited availability of prenatal
concern worldwide, affecting nearly 15 million
ultrasounds and the unreliability of last
births in 2014 (10.6% of the total births [1]).
menstrual period as an indicator of gestational
Complications resulting from preterm birth are
age (GA) due to imperfect recall and
the leading cause of death among children under
documentation [4,5]. In addition, in many
five, accounting for 35% of all global neonatal
settings, preterm birth estimates are not
deaths in 2016 [1]. Infants who survive are at
reported or are not classified according to
increased risk of a variety of complications,
internationally accepted standards [6]. These
including cerebral palsy, sensory deficits,
limitations are significant, as accurate estimates
respiratory illness, and poorer cardiometabolic
of GA are important at both a population and
outcomes [2,3].
individual level. Without comprehensive
Rates of preterm birth vary considerably by population-level data, appropriate resource
geographic region, with 2014 estimates ranging allocation and program evaluation to support

2
local and global health initiatives are impeded. At
the individual level, accurate GA knowledge can
help to direct care, particularly for term small-
for-gestational-age (SGA) infants, who may
appear similar to preterm infants in terms of size
and birth weight. The ability to distinguish term
SGA from preterm infants directly impacts both
clinical decision-making and expectations for the
achievement of developmental milestones.
In the absence of gold-standard prenatal
ultrasound technology, several postnatal GA
measurements exist, including the Ballard and
Dubowitz scores, both of which are based on
physical and neurological assessments of
developmental milestones that occur in a
predictable sequence over time [7–9]. A recent
systematic review of GA assessment methods
indicated that the Dubowitz score dates 95% of
pregnancies to within ±2.6 weeks of ultrasound-
estimated GA, while the Ballard score dates
pregnancies to within ±3.8 weeks of ultrasound-
estimated GA [10]. Another approach to
postnatal GA estimation is through the
evaluation of the newborn’s anterior lens
capsule vascularity (ALCV); the disappearance of
ALCV is a normal embryological process that
occurs between 27- and 34-weeks’ gestation
CONTACT Kumanan Wilson kwilson@ohri.ca Ottawa Hospital, Civic Campus, 1053 Carling Avenue, Box 684, Administrative Services Building, Ottawa ON
K1Y 4E9, Canada
© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
[11]. ALCV can be evaluated within 48 h of birth
and is a good indicator of preterm birth
(correlation: −0.719 [12]), as the vessels are
usually completely resorbed by 35 weeks’
gestation [11]. This approach is highly dependent
on environmental conditions, requires access to
technology capable of producing highquality
images, and is of limited utility in identifying late
preterm infants with a gestational age above 35
weeks [12]. The low level
728 L. A. WILSON ET AL.
Article Highlights
● Preterm birth is a major global health concern,
contributing to 35% of all neonatal deaths in 2016.
3
Complications resulting from preterm birth are the
leading cause of death among children under five,
accounting for 35% of all global neonatal deaths in 2016.
● The circulating metabolites measured during newborn
screening are known to be affected by gestational age,
and many of these metabolites are measured during
routine newborn screening. Thus, we sought to explore
the potential for newborn screening-based metabolomics
to offer additional insights into rates of preterm birth.
● Leveraging 2 years of health administrative and newborn
screening analyte data from NSO for approximately
250,000 infants, our group developed an algorithm
capable of accurately estimating GA to within 1.06 weeks
of ultrasound-validated GA.
● We then explored the addition of fetal-to-adult
hemoglobin ratios into our model, and validated model
performance among infants of immigrant mothers in
Canada and a cohort of infants in Matlab, Bangladesh.
● Our ongoing efforts to improve the precision of our
models in a variety of settings have demonstrated that
metabolomics techniques may be used to generate
estimates of GA that are accurate to within 1–2 weeks of
ultrasound-derived GA. Future enhancements will be
based on applying novel machine learning techniques to
improve the accuracy of our models, and developing
point of care testing to improve the intervention’s cost-
effectiveness.
of invasiveness and low cost of these measures
are important considerations for implementation
in low-income settings, but these methods are
also subject to a high level of inter-user
variability, are affected by factors such as
ethnicity and geography, and have limited
accuracy, particularly among preterm and SGA
infants [7–10].
Given the importance of accurately ascertaining
estimates of preterm birth and in light of current
limitations in postnatal GA estimation, novel
methods of estimating GA postnatally in the
absence of prenatal ultrasound are urgently
required. Previous and ongoing work conducted
by our research group and others has
demonstrated the potential for metabolomics to
fill this gap. Metabolomics refers to the use of
liquid chromatography and mass spectrometry
for the ‘quantitative cataloging’ of metabolites in
a biological sample [13]. Concentrations of
metabolites in such samples may reflect
underlying biological processes that are
associated with fetal maturation and thus may
correlate with gestational age. Newborn
screening programs in many countries already
use biological samples collected during the
neonatal period to measure a range of
metabolites. Thus, we sought to explore the
potential for newborn screening-based
metabolomics to offer additional insights into
rates of preterm birth.
2. Associations between gestational age
andcirculating analytes in newborns
Newborn screening programs are public health
initiatives intended to identify infants at risk of
rare, treatable diseases that do not typically
show symptoms during the neonatal period.
Newborn screening programs in high-income
settings may screen infants for as many as 50
different conditions [14]. Screening usually
involves collecting a small sample of blood from
an infant’s heel during the first few days of life
[15]. Tandem mass spectrometry (MS/MS) is
used for expanded newborn screening programs
that target metabolic diseases via the analysis of
amino acids and acylcarnitines. Other analytes,
including 17-hydroxyprogesterone (17-OHP) and
thyroid-stimulating hormone (TSH) for screening
of congenital adrenal hyperplasia and congenital
hypothyroidism, respectively, are typically
analyzed by immunoassay. Hemoglobin analysis
for sickle cell disease and other
hemoglobinopathies is facilitated by isoelectric
focusing or high-performance liquid
chromatography (HPLC), and polymerase chain
reaction may be used to confirm genetic
abnormalities.
The circulating metabolites measured during
newborn screening are known to be affected by
GA, a factor that is considered in the
interpretation of newborn screening results [16].
Amino acids including arginine, leucine, and
valine differ by as much as 50% between
extremely preterm and term infants [17]. These
variations may reflect higher levels of catabolism
or delays in hepatic maturation among preterm
4
infants. Newborn 17-OHP and TSH levels are also
significantly correlated with GA at birth [17].
Levels of 17-OHP increase with increasing levels
of prematurity, potentially due to heightened
levels of neonatal stress. By contrast, levels of
TSH can be as much as 60% lower among
preterm infants compared to term infants, likely
as a result of decreased thyroid and pituitary
development [17].
In Ontario, Canada, nearly every infant born in
the province undergoes newborn screening, and
the results of this screening, including the
individual analyte levels and key demographic
variables, are stored by Newborn Screening
Ontario (NSO), the provincial newborn screening
program, until the child’s 19th birthday.
Leveraging 2 years of linked health
administrative and newborn screening analyte
data from NSO for over 250,000 infants, our
group developed an algorithm capable of
accurately estimating GA to within 1 week of
ultrasound-validated GA [18]. Model
performance was evaluated across multiple birth
categories: ≥37, 33–36, 28–32, ≤27 weeks’
gestation, and ≤34 and <37 weeks’ GA. Ryckman
and colleagues at the University of Iowa and
Jeliffe-Pawlowski and colleagues at the
University of California, San Francisco used
similar approaches to develop models capable of
differentiating preterm from term births using
data derived from 230,013 infants and 729,503
infants, respectively [19,20]. A summary of these
approaches and their successes is provided in
Table 1.
3. Model refinement and ethnic
validation
After determining the functionality of this
approach, it was important to assess the validity
of the algorithm in different ethnic populations
as a first step to determining its applicability in
other countries. Birth weight, a significant
predictor in all of our GA estimation models, is
strongly correlated with GA and varies
considerably by ethnicity; infants of European
descent tend to have larger birth weights than
 other infants [21]. Infants of East Asian descent,
who have a lower mean birth weight than other
infants, are prone to misclassification as SGA
when born in Western countries and assessed
against growth curves derived in Western
populations [22,23]. As our original GA
estimation model was based on data from a
sample of predominantly white infants and
included birth
EXPERT REVIEW OF PROTEOMICS
729
weight among its model predictors, we
conducted a retrospective validation study using
data from infants in Ontario whose mothers
were recent landed immigrants and compared
model performance to that of infants born to
mothers not identified as landed immigrants. In
this way, we sought to determine whether one
global algorithm would be adequate for
estimating GA across ethnic subgroups, or
whether local model calibration would likely be
required in each new setting. Our results
‘term’ or ‘preterm’.LMP:LastMenstrualPeriod
relationship between the ratio of fetal-to-adult
hemoglobin (Hb) levels and GA [25], and the
relative ease of measuring Hb levels compared to
other newborn screening analytes (measured by
HPLC versus MS/MS), we investigated the ratio
of fetal-to-adult Hb as a potential new predictor
of GA in our original Ontario sample. Though
insufficient to predict GA on its own, the ratio of
fetal-to-adult Hb in combination with clinical
factors such as sex and birthweight estimated GA
better than clinical covariates alone and
improved upon the performance of our original
Ontario-based algorithm described above [26].
Notably, Hb levels are relatively consistent and
stable between blood spot samples taken via
cord blood and heel-prick [27]. This differs from
other analytes that fluctuate in the first few days
after birth and may be inconsistent between
cord and heel-prick blood spot samples due to
differences in timing of collection. This
consistency also has important implications in
low-resource settings where there may be
parental and/or health-care provider hesitancy
surrounding heel-prick procedures, particularly
among preterm infants [27].
4. International implementation

indicated that tailored algorithms may help to

improve the precision of GA estimation, but our
model performed well among infants from a
variety of ethnic backgrounds [24], although
there was some variation in accuracy of GA
estimation. Among non-immigrant mothers, the
model estimated GA to within an average of 1.05
weeks of true GA, while among immigrant
mothers, estimates ranged from 0.98 to 1.15
weeks of true GA [24]. This suggested that our
Prematurity and Stillbirth (GAPPS). Health-care
global model could perform well across a wide
eeks ’ gestationwhere99.5%oftheinfantswerecorrectlyclassifiedas
Having demonstrated proof-of-principle for
metabolic estimation of GA, the effectiveness
and practicality of using this approach in low-
resource settings needed to be established. In
2016, we embarked upon a prospective
validation study in Matlab, Bangladesh, nested
within an existing preterm birth cohort
established by the Global Alliance to Prevent

providers collected paired dried heel-prick and

variety of settings but might be further improved
cord blood samples from the newborns of
through local calibration in new settings.
consenting mothers and gathered demographic
Recognizing that establishing new routine data from the mother-child pairs. The dried
newborn screening programs in low-income blood spot samples were then shipped to
settings may be hindered by technological and Ottawa, Canada for analysis at NSO
resource requirements, we also sought to refine
the model to facilitate its implementation in
these settings. Because of the known

5
 *modelperformanceamongstpreterminfantsonly,
weeksoftruegestationalage(%)
A total of 1,036 cord blood and 487 heel-prick samples were
collected from 1,069 unique newborns. Collecting both heel-
prick and cord blood samples enabled both validation of the
model overall and evaluation of its relative performance in
both sample types.When applied to heel-prick data, our
algorithms estimated GA to within 1.07 weeks of ultrasound-
validated GA overall, and correctly estimated GA to within 2
weeks for 94% of the infants. While model performance was
slightly reduced when applied to data derived from cord blood
samples, GA was correctly estimated to within 2 weeks for
over 90% of the infants. These findings are encouraging, as
cord blood sampling was more widely accepted by parents
than heel-prick sampling due to concerns around causing
discomfort to the infant or lack of understanding of the
procedure. Health-care providers also reported being more
comfortable collecting cord blood samples. The increased
acceptability and uptake of cord blood sampling are an
important consideration going forward if metabolic gestational
aging approaches are to be scaled up to other settings.
Importantly, the model performed especially well among
infants whose birthweight was
Our approach is now being implemented in real-world
settings in sub-Saharan Africa and South-East Asia, in
populations where prenatal care and use of gestational-dating
ultra sounds are not widespread. In partnership with
investigators at Stanford University, this initiative will result
in prospective collection of heel-prick and cord blood samples
from infants in Kenya, Zambia, Zimbabwe, and Bangladesh,
permitting us to further define the accuracy of our algorithms
in both types of samples, with a particular emphasis on cord
blood.
5.Conclusion It is well established that a difference in
GA at birth of as little as 1 week can have significant impacts
on neonatal morbidity, mortality, and long-term outcomes
[28,29]. A problem in current clinical approaches to preterm
infants is the limited availability of postnatal GA assessment
tools that are both non-invasive and accurate, particularly
among preterm and SGA infants. Evidence suggests that
metabolomics techniques may be used to generate estimates
of GA that are accurate to within 1–2 weeks of ultrasound-
derived GA [18–20]
6. Expert opinion Our modeling approach has evolved
considerably over time and has now expanded to include
advanced machine learning techniques to better
accommodate large numbers of predictors relative to sample
size, to incorporate flexible non-linear modeling of
predictoroutcome associations, and to incorporate interaction
effects among predictors and outcome. In order to better
tailor our models as they are deployed in each new setting,
we are developing model calibration and updating strategies
to optimize model performance
6
for local conditions. Calibration and updating in this
yielding dramatic improvements in the accuracy of pr
and estimation.
We are also exploring state-of-the-art artificial inte
(AI) modeling approaches such as deep learning
networks (DLNN). The most advanced methods can
much larger datasets with many more predictors
identify and exploit more complex features in pu
highly accurate models, but these benefits come at the
more challenging interpretation and resource intens
Although promising, these more advanced predict
estimation models may provide diminishing returns co
to our latest conventional models with machine
enhancements.
We are also undertaking studies that will exam
potential for an untargeted metabolomic approach to
our ability to estimate GA postnatally and to identify
at risk for a variety of conditions. The metabolites c
included in our GA model are restricted to those trad
obtained through newborn screening and require
exploration to better elucidate their relationship to G
use of a broader spectrum of analytes may incre
accuracy of our model.
We continue to strive to enhance our approach to
its feasibility and acceptability. A major challenge
metabolomics approach to postnatal GA dating
requisite use and expertise of advanced laboratory tec
and resources to analyze biological samples. Previo
has demonstrated the feasibility of international te
newborn samples, but such approaches are not econo
sustainable in the long term [27]. For instance,
Bangladesh cohort, the cost for shipment and analysis
sample was approximately USD$50.00, excluding
start-up and maintenance costs. To address this, w
explored and continue to develop partnership
established newborn screening programs in closer geo
proximity to sampling sites. We are also exploring
approach to GA estimation that is based on birthwe
adapted to the region in which it is being implement
This approach would assume that infants above a
weight threshold are term and would not require
testing. Below a certain weight threshold, infants c
classified as ‘potentially preterm’ and GA could be e
using existing postnatal GA estimation measures,
Anterior Lens Capsule Vascularity measurement whi
between thresholds could undergo metabolomic GA
Additionally, adaptation of our model for reliable use
blood-derived data will likely enhance the acceptab
sample collection methods by family members and
care providers who have expressed reticence about he
sampling. By addressing these challenges, we may
approach transition from a method of populati
surveillance to a tool that could be used to guide
individual infants.
7
Funding
This research was supported by the Bill &
Melinda Gates Foundation, grants:
[OPP1141535 and OPP1184574].
Declaration
of interest The authors have no relevant
affiliations or financial involvement with any
organization or entity with a financial interest
in or financial conflict with
the subject matter or materials discussed in
the manuscript. This includes employment,
consultancies, honoraria, stock ownership or
options, expert testimony, grants or patents
received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no
relevant financial or other relationships to
disclose
3. World Health Organization. WHO | New global
estimates on preterm birth published [Internet].
Sex. Reprod. Heal. World Health Organization;
2018 [cited 2019 Jun 11]. Available from:
https://www.
who.int/reproductivehealth/global-estimates-
preterm-birth/en/
4. Baird DD, McConnaughey DR, Weinberg CR, et
al. Application of a method for estimating day of
ovulation using urinary estrogen and
progesterone metabolites. Epidemiology
[Internet]. 1995;6:547–550. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/8562634
5. Nakling J, Buhaug H, Backe B. The biologic
error in gestational length related to the use of
the first day of last menstrual period as a proxy
for the start of pregnancy. Early Hum Dev
[Internet]. 2005;81:833–839. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/16084037

ORCID
Lindsay A. Wilson http://orcid.org/0000-
0002-9910-3338 Steven Hawken
http://orcid.org/0000-0002-3341-9022

References Papers of special note have been

highlighted as either of interest (•) or of
considerable interest (••) to readers.
1. Chawanpaiboon S, Vogel JP, Moller A-B, et
al. Global, regional, and national estimates of
levels of preterm birth in 2014: a systematic
review and modelling analysis. Lancet Glob
Health [Internet]. 2019;7:e37–e46. Available
from: https://linkinghub.elsevier.com/
retrieve/pii/S2214109X18304510 •• Overview
of current burden of preterm birth
internationally.
2. Saigal S, Doyle LW. An overview of mortality
and sequelae of preterm birth from infancy to
adulthood. Lancet [Internet]. 2008;371:261–
269. Available from:
https://linkinghub.elsevier.com/
retrieve/pii/S0140673608601361

8
9
6. Quinn J-A, Munoz FM, Gonik B, et al. Preterm birth:
case definition & guidelines for data collection,
analysis, and presentation of immunisation safety
data. Vaccine [Internet]. 2016;34:6047–6056.
Available from:
http://linkinghub.elsevier.com/retrieve/pii/S0264410
X16300287 7. Alexander GR, de Cannes F, Hulsey TC,
et al. Validity of postnatal assessments of gestational
age: a comparison of the method of Ballard et al. and
early ultrasonography. Am J Obstet Gynecol.
1992;166:891–895.
8. Spinnato JA, Sibai BM, Shaver DC, et al. Inaccuracy
of Dubowitz gestational age in low birth weight
infants. Obstet Gynecol. 1984;63:491–495.
9. Robillard PY, de Caunes F, Alexander GR, et al.
Validity of postnatal assessments of gestational age in
low birthweight infants from a Caribbean community
8071. J.Perinatol. 1992;12:115–119.
10. Lee AC, Panchal P, Folger L, et al. Diagnostic
accuracy of neonatal assessment for gestational age
determination: a systematic review. Pediatrics
[Internet]. 2017;140:e20171423. Available from:
http://
pediatrics.aappublications.org/lookup/doi/10.1542/p
eds.2017-1423 • Systematic review of current
methods of GA estimation; provides comparison of
accuracy between methods.
11. Patel M, Mukherjee D, Farsiu S, et al. Estimation of
gestational age via image analysis of anterior lens
capsule vascularity in preterm infants: a pilot study.
Front Pediatr [Internet]. 2019;7. Available from::
https://www.frontiersin.org/article/10.3389/fped.201
9. 00043/full
12. Desai AD, Peng C, Fang L, et al. Open-source,
machine and deep learning-based automated
algorithm for gestational age estimation through
smartphone lens imaging. Biomed Opt Express
[Internet].2018 9:6038. Available from:
https://www.osapublishing.org/abstract. cfm?
URI=boe-9-12-6038
10
13. Griffiths WJ, Wang Y. Mass
spectrometry: from proteomics to
metabolomics and lipidomics. Chem Soc
Rev [Internet]. 2009;38:1882. Available
from: http://xlink.rsc.org/?
DOI=b618553n
14. Therrell BL, Padilla CD, Loeber JG, et
al. Current status of newborn screening
worldwide: 2015. Semin Perinatol.
2015;39:171–187.
15. Newborn Screening Ontario.
Backgrounder on newborn screening
Ontario (NSO) What is newborn
screening? What is NSO? 2017;8330.
16. Oladipo OO, Weindel AL, Saunders
AN, et al. Impact of premature birth and
critical illness on neonatal range of
plasma amino acid concentrations
determined by LC-MS/MS. Mol Genet
Metab. 2011;104:476–479.
17. Wilson K, Hawken S, Ducharme R, et
al. Metabolomics of prematurity: analysis
of patterns of amino acids, enzymes, and
endocrine markers by categories of
gestational age. Pediatr Res [Internet].
2014;75:367–373. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/2
4216540 •• Original article examining
variation in newborn screening analytes
as GA increases.
18. Wilson K, Hawken S, Potter BK, et al.
Accurate prediction of gestational age
using newborn screening analyte data.
Am J Obstet Gynecol [Internet].
2016;214:513.e1–513.e9. •• Original
model developed to estimate GA based
on newborn screening analytes using
Ontario samples
19. Ryckman KK, Berberich SL, Dagle JM.
Predicting gestational age using neonatal
metabolic markers. Am J Obstet Gynecol
[Internet]. 2016;214:515.e1–515.e13.
20. Jelliffe-Pawlowski LL, Norton ME, Baer RJ, et 27. Murphy MS, Hawken S, Cheng W, et al.
al. Gestational dating by metabolic profile at External validation of postnatal gestational age
birth: a California cohort study. Am J Obstet estimation using newborn metabolic profiles in
Gynecol [Internet]. 2016;214:511.e1–511.e13. Matlab, Bangladesh. Elife [Internet]. 2019;8.
21. Ray J, Sgro M, Mamdani M, et al. Birth Available from:
weight curves tailored to maternal world https://elifesciences.org/articles/42627 ••
region. J Obstet Gynaecol Canada. Article covering international validation study in
2012;34:159–171. Matlab, Bangladesh.
22. De Souza LR, Urquia ML, Sgro M, et al. One 28. Parikh LI, Reddy UM, Männistö T, et al.
size does not fit all: differences in newborn Neonatal outcomes in early term birth. Am J
weight among mothers of Philippine and other Obstet Gynecol [Internet]. 2014;211:265.e1–
East Asian Origin. J. Obstet. Gynaecol. Canada 265.e11. Available from:
[Internet]. 2012;34:1026–1037. Available from: https://linkinghub.elsevier.com/retrieve/pii/
https://linkinghub.elsevier. S0002937814002269
com/retrieve/pii/S1701216316354329 29. Boyle EM, Poulsen G, Field DJ, et al. Effects
23. Ray JG, Jiang D, Sgro M, et al. Thresholds for of gestational age at birth on health outcomes
small for gestational age among newborns of at 3 and 5 years of age: population based cohort
East Asian and South Asian Ancestry. J. Obstet. study. BMJ [Internet]. 2012;344:e896–e896.
Gynaecol. Canada [Internet]. 2009;31:322–330. Available from:
Available from: https://linkinghub.els http://www.bmj.com/cgi/doi/10.1136/bmj.e896
evier.com/retrieve/pii/ S1701216316341494
24. Hawken S, Ducharme R, Murphy MSQ, et al.
Performance of a postnatal metabolic
gestational age algorithm: a retrospective
validation study among ethnic subgroups in
Canada. BMJ Open [Internet]. 2017;7:e015615.
Available from: http://bmjopen.bmj.
com/lookup/doi/10.1136/bmjopen-2016-
015615 •• Ethnic validation study examining
accuracy of model among infants born to
immigrant mothers in Ontario.
25. Thein SL, Menzel S, Lathrop M, et al.
Control of fetal hemoglobin: new insights
emerging from genomics and clinical
implications. Hum Mol Genet. 2009;18:216–
223.
26. Wilson K, Hawken S, Murphy MSQ, et al.
Postnatal prediction of gestational age using
newborn fetal hemoglobin levels. EBioMedicine
[Internet]. 2017;15:203–209. •• Article
exploring inclusion of adult-to-fetal hemoglobin
ratio in GA estimation model.

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 BAB III
PEMBAHASAN

3.1 Profile Penelitian

3.1.1 Judul penelitian : Postnatal gestational age estimation via newborn screening
analysis:application and potential
3.1.2 Pengarang : Lindsay A. Wilson a , Malia SQ. Murphya , Robin
Ducharmea ,Kathryn Denizeb , Nafisa M. Jadavjia , Beth
Potterc , Julian Littlec , Pranesh Chakrabortyb , Steven
Hawken a and Kumanan Wilsona
3.1.3 Sumber : Taylor and francis, 2019

3.1.4 Major/minor subject : Gestational age; metabolomics; newborn screening

3.1.5 Abstract : Introduction: Preterm birth is a major global health concern,
contributing to 35% of all neonatal deaths in 2016. Given the
importance of accurately ascertaining estimates of preterm birth
and in light of current limitations in postnatal gestational age
(GA) estimation, novel methods of estimating GA postnatally in
the absence of prenatal ultrasound are needed. Previous work has
demonstrated the potential for metabolomics to estimate GA by
analyzing data captured through routine newborn screening.
Areas covered: Circulating analytes found in newborn blood
samples vary by GA. Leveraging newborn screening and
demographic data, our group developed an algorithm capable of
estimating GA postnatally to within approximately 1 week of
ultrasound-validated GA. Since then, we have built on the model
by including additional analytes and validating the model’s
performance through internal and external validation studies, and
through implementation of the model internationally. Expert
opinion: Currently, using metabolomics to estimate GA
postnatally holds considerable promise but is limited by issues of
cost-effectiveness and resource access in low-income settings.
Future work will focus on enhancing the precision of this
approach while prioritizing point-of-care testing that is both
accessible and acceptable to individuals in low-resource settings.
3.1.6 Publikasi : 2019

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3.2 Deskripsi Penelitian berdasarkan metode PICO :

a. Tujuan penelitian : Penelitian ini bertujuan untuk mengkaji

pengaplikasian dan potensi penggunaan metode
metabolik yang sudah diteliti sebelumnya dalam
memperkirakan GA Postanal yang non-invasif
dan akurat khususnya pada bayi premature

b. Desain penelitian : Memanfaatkan data analit administrasi kesehatan

dan skrining bayi baru lahir selama 2 tahun dari
NSO untuk sekitar 250.000 bayi, kelompok kami
mengembangkan algoritme yang mampu
memperkirakan GA secara akurat hingga 1,06
minggu dari GA yang divalidasi dengan
ultrasound.

c. Populasi/ sample and problem :  bayi yang berisiko terhadap penyakit langka yang
dapat diobati yang biasanya tidak menunjukkan
gejala selama periode neonatal. menargetkan
penyakit metabolik melalui analisis asam amino
dan asilkarnitin. Analisis lain, termasuk 17-
hidroksiprogesteron (17-OHP)

d. Intervensi : Program skrining bayi baru lahir adalah inisiatif

kesehatan masyarakatdimaksudkan untuk
mengidentifikasi bayi yang berisiko terkena
penyakit langka yang dapat diobatiyang biasanya
tidak menunjukkan gejala selama neonatusTitik.
Program skrining bayi baru lahir di lingkungan
berpenghasilan tinggidapat menyaring bayi untuk
sebanyak 50 kondisi yang berbeda. Skrining
biasanya melibatkan pengumpulan sedikit sampel
darah dari tumit bayi selama beberapa hari
pertama kehidupan. program skrining bayi baru
lahir yang menargetkan penyakit
metabolikmelalui analisis asam amino dan
asilkarnitin. Ana lainnyalytes, termasuk 17-
hydroxyprogesterone (17-OHP) dan thyr-oid-
stimulating hormone (TSH) untuk skrining
kongenitalhiperplasia adrenal dan hipotiroidisme
kongenital, masing-masing biasanya dianalisis
dengan immunoassay. Hemoglobin analisis
untuk penyakit sel sabit dan hemoglobinopati
lainnya difasilitasi oleh pemfokusan isoelektrik
atau cairan kinerja tinggi kromatografi (HPLC),

13
 dan reaksi berantai polimerase mungkin
digunakan untuk mengkonfirmasi kelainan
genetik
e. Comporation :-

f. Outcomes : Sudah diketahui bahwa perbedaan GA saat lahir hanya dalam

waktu 1 minggu dapat memiliki dampak yang signifikan pada
morbiditas, mortalitas, dan hasil jangka panjang neonatus.
Masalah dalam pendekatan klinis saat ini untuk bayi prematur
adalah terbatasnya ketersediaan alat penilaian GA postnatal
yang non-invasif dan akurat, khususnya di antara bayi prematur
dan SGA. Bukti menunjukkan bahwa teknik metabolomik dapat
digunakan untuk menghasilkan perkiraan GA yang akurat
dalam 1-2 minggu GA yang diturunkan dari ultrasound

g. Kelebihan : 1. Memaparkan informasi lengkap tentang kelahiran

premature. Informasi tersebut meliputi faktor factor
kelahiran prematur, resiko kelahiran prematur dan
sebagainya, bahkan informasi yang disampaikan ke
tingkat metabolic penyebab kelahiran premature
2. Penelitian dilakukan secara spesifik dan sangat mendalam
bahkan melibatkan alat dan teknologi yang canggih,
sehingga hasilnya lebih valid

Kekurangan : Peneliti sering menyebutkan bahwa penelitian ini

merupakan lanjutan dari penelitian sebelumnya,
namun tidak menambahkan informasi terkait artikel
penelitian sebelumnya yang dimaksud

h. Manfaat Penelitian : 1. Menguasai serta memahami teori keperawatan

yakni peran kolaboratif perawat dalam pemberian
edukasi pada pasien
2. Mengetahui betapa pentingnya menjaga asupan dan
kondisi tubuh untuk ibu hamil guna menghindari
kelahiran premature

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 BAB IV
PENUTUP

4.1 Kesimpulan
Kelahiran premature merupakan kondisi dimana bayi lahir sebelum waktu
yang ditentukan. Dari permasalahan ini diperlukan metode pencegahan kelahiran
premature ini. Pada penelitian ini, peneliti mencoba membuktikan bahwa penting
dilakukan screening kesehatan baik pra maupun pasca kelahiran dan kelahiran.
Screening ini sangat penting dilakukan guna mengantisipasi adanya kelahiran
premature. Metode yang dilakukan peneliti adalah pengecekan secara fisik dan juga
metode metabolomics. Metabolomic merupakan metode lanjutan analisis data dari
hasil screening bayi baru lahir yang telah dilakukan. Metode ini agak sulit diterapkan
secara komersial karena membutuhkan teknologi medis dan laboratorium yang
canggih, sehingga hanya beberapa Negara maju yang bisa menerapkan metode ini.

4.2 Saran
Dalam melakukan penelitian ini, perlu dilakukan penelitian lebih lanjut terkait
pemerataan implementasi dari metode. Hal ini dimaksudkan agar metode tersebut bisa
merata dan bisa membantu banyak orang untuk mencegah maupun menangani
kelahiran premature.

15
 DAFTAR PUSTAKA

Chawanpaiboon S, Vogel JP, Moller A-B, et al. Global, regional, and national estimates of
levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob
Health [Internet].
Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to
adulthood. Lancet [Internet].
World Health Organization. WHO | New global estimates on preterm birth published
[Internet]. Sex. Reprod. Heal. World Health Organization; 2018 [cited 2019 Jun 11]

16
 LAMPIRAN 1

LOOG BOOK

Judul : Postnatal gestational age estimation via newborn

screening analysis: application and potential
Pelaksana : MOH. HAKIM SETYA NEGARA
Tanggal : 13 Oktober 2021

Saya memberikon tribusi kelompok ini dengan :

Mencari bahan materi berdasarkan literature terpercaya menganalisi isi jurnal

Berikutnya, saya akan :

Menganalisis jurnal berdasarkan Metode PICO

Tuliskan pengalaman anda setelah mengerjakan proyek ini :

Merasa lebih mengetahui manajemen terealisasi keperawatan terkini yang dapat

diterapkan kepada pasien
Tuliskan kemampuan apa saja yang seharusnya anda miliki agar proyek terlaksana
dengan baik :
Manajemen waktu dan ketelatenan dalam menganalisis jurnal berdasarkan Metode
PICO

1 = Sangat Tidak Setuju 2 = Tidak Setuju 3=Setuju 4=Sangat Setuju

Semua anggota berkontribusi yang sama dalam proyek ini     V  
Kelompok kami bekerja keras dalam proyek ini     V  
Ketidaksamaan pendapat telah diselesaikan tugas sesuai jadwal
yang telah dibuat      V  
Saya merasa diberi semangat oleh kelompok kami untuk dapat
bekerja baik di proyek ini      V
Saya ingin bergabung lagi dengan kelompok ini       V

LAMPIRAN 2

17
 LEMBAR KONSULTASI PRESENTASI JURNAL

JUDUL: Postnatal gestational age estimation via newborn screening analysis: application
and potential
TTD
No HARI/TANGGAL MATERI KONSULTASI PEMBIMBING
KONSULTASI DOSEN
1.
KONSULTASI JUDUL :

2.
KONSULTASI ANALISIS JURNAL :

3.
KONSULTASI PENYUSUNAN
LAPORAN JURNAL :

4.
KONSULTASI SLIDE PRESENTASI :

TTD ACC PRESENTASI JURNAL

____________

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