TITLE: Algorithm for gestational age assessment at birth
AUTHORS: Zilma Reis, Juliano de Souza Gaspar, Sara Oliveira Elias, Regina Amelia Lopes Pessoa De Aguiar

[DESCRIPTION]
<div class = "text-blocks"><div class = "text-block">This protocol presents an algorithm for gestational age assessment when a reliable last menstrual period or an obstetric ultrasound are available in the birth scenario. A software was developed to automatically process data entries into the best estimative of the gestational age at birth. </div><div class = "text-block">It shall be used by the multicenter team of researchers, duly trained in accordance with the Good Clinical Practice Protocol, during the enrollment of newborns. Also, this protocol is complementary documentation for the scientific publications related to the clinical trials:</div><div class = "text-block"><span>"Prematurity detection evaluating interaction between the skin of the newborn and light: protocol for the preemie-test multicentre clinical trial in Brazilian hospitals to validate a new medical device"; Register number </span><a href="http://ensaiosclinicos.gov.br/rg/RBR-3f5bm5" style = "text-decoration:underline;color:blue;cursor:pointer;"><span style = ":;">RBR-3f5bm5</span></a><span style = ":;">.</span></div><div class = "text-block"><span>"Premature or small for gestational age? International multicenter trial protocol for classification of the low birth weight newborn through the optical properties of the skin"; Register number </span><a href="http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-33rnjf" style = "text-decoration:underline;color:blue;cursor:pointer;"><span style = ":;">RBR­33rnjf</span></a><span>.</span></div></div>

[STEPS]
?. [Menstrual cycle reference]
The last menstrual period reference

The interview aims to qualify the information about the last menstrual period, in terms of its reliability.
?. [Menstrual cycle reference]
The last menstrual period assessment to assist gestation age calculation is based on an interview with women and documentary analysis.   To achieve a reliable last menstrual period reference, the researcher will interview the woman using the questions as follows, adapted from Nguyen et al. 2000 report:    
Question 1: When did your last menstrual period occur? Please, confirm if it was the first day of menstruation.    Question 2: Are you sure about this date?  
Question 3: Are your menstrual cycles regulars? Clarify her that it was when the duration of the cycles did not change for more than one week.     Question 4: Two months before your last menstrual period, did you use any contraceptive method, like pills, injections, Mirena IUD, skin implant, vaginal ring?  Question 5: Two months before your last menstrual period, had you an abortion or delivered a child?
?. [Menstrual cycle reference]
For further double-check, take a picture of the personal prenatal care book where the last menstrual period is reported. Make sure she permitted you for this step. 


Make sure the informed date is the same reported in the personal prenatal care book, to avoid memory recall bias.
?. [Ultrasound reference]
The first obstetric ultrasound referenceThis step aims to assess the best antenatal ultrasound record to assist the gestational age calculation at birth. When the assessment occurred between 7w+0d and 13w+6d of pregnancy, the crow-rump-length (CRL) measurement of the embryo is the primary reference. The research should certify the source of information, preferably the value of   CRL.
?. [Ultrasound reference]
Chronologically organize the antenatal obstetric ultrasound reports. 


Select the first gestational assessment with an available CRL measurement, among 7w+0d and 13w+6d of pregnancy. 


Take note of the assessment date and the reported gestational age at this time. When gestational age is incomplete as 7/8 weeks, consider 3 days: 7w+3d.


Take note of the CRL measurement, when available even in the embryo image. 





Crown-rump-length (CRL) measurement

Gestational age will be adjusted according to Intergrowth’s 21st standard curve for ultrasound CRL measurements using the International Fetal Size in Early Pregnancy from 7 weeks and 3 days up to 13 weeks and 6 days (Papageorghiou AT et al., 2014).
?. [Ultrasound reference]
Take a picture of the reference ultrasound report if available or the personal prenatal care book where the ultrasound result is reported. Make sure she permitted you for this step.
?. [Automated algorithm]
Gestational age assessment, according to an automated algorithmFor this step, we developed software to process pregnancy dating at birth following the best practice for gestational age calculation. The algorithm automates methods like the following scientific references recommendations:Adjustment of CRL to the Intergrowth-21st reference: PapageorghiouAT, Kennedy SH, Salomon LJ, et al.International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.Ultrasound Obstet Gynecol 2014;44:641–8. DOI:10.1002/uog.13448Reliable last menstrual period concept: Nguyen TH, Larsen T, Engholm G, et al. Increased adverse pregnancy outcomes with unreliable last menstruation.Obstet Gynecol2000;95(6 Pt 1):867–73. DOI:10.1016/s0029-7844(99)00639-0Gestational age at birth assisted by the CRL measurement or the last menstrual period: Committee on Obstetric Practice, the Society for Maternal-Fetal Medicine. Committee Opinion No 700: Methods for estimating the due date. Obstet Gynecol. 2017;129(5):e150-4. PMID: 28426621. DOI: 10.1097/AOG.0000000000002046.
?. [Automated algorithm]
DetailsInsert data in the information system entries:  ABC1VariableDataDetalis2LMP_DateDate of the last menstrual periodDate3LMP_1Question 1Yes/ No4LMP_2Question 2Yes/ No5LMP_3Question 3Yes/ No6LMP_4Question 4Yes/ No7LMP_5Question 5Yes/ No8LMP_GA_DaysNumber of days between the LMP_Date and the Childbirth_DateDate9US_CRLCrown-rump-length (mm) reported in the ultrasoundValue10GA_CRLGestational age reported in the reference ultrasound (days)Value11Childbirth_DateDate of the childbirthDate12US_DateDate of the reference obstetric ultrasoundDate13US_GAGestational age reported in the reference ultrasound (days)Value14DIFFDay difference calculated by the LMP and US days of pregnancyValue15DB_IntergrowthDatabase with Intergrowth’s 21st standard curve for US CRLReference values
ABC1VariableDataDetalis2LMP_DateDate of the last menstrual periodDate3LMP_1Question 1Yes/ No4LMP_2Question 2Yes/ No5LMP_3Question 3Yes/ No6LMP_4Question 4Yes/ No7LMP_5Question 5Yes/ No8LMP_GA_DaysNumber of days between the LMP_Date and the Childbirth_DateDate9US_CRLCrown-rump-length (mm) reported in the ultrasoundValue10GA_CRLGestational age reported in the reference ultrasound (days)Value11Childbirth_DateDate of the childbirthDate12US_DateDate of the reference obstetric ultrasoundDate13US_GAGestational age reported in the reference ultrasound (days)Value14DIFFDay difference calculated by the LMP and US days of pregnancyValue15DB_IntergrowthDatabase with Intergrowth’s 21st standard curve for US CRLReference values
?. [Automated algorithm]
Decision-tree details
?. [Experts checking and adjustments]
A team of researchers-experts has a role in rechecking the data, according to sources as photos of ultrasound reports, the digital image of the CRL, the digital copies of the personal prenatal care book. This procedure demands access to the database simultaneously with the digital images.    After one-by-one of the newborns' data double-checking, gestational age obtained at birth should be adjusted to mirror the registered information when the original data was recollected. 


Once more, the algorithm will process the optimal dating gestational age at birth.
?. [Experts checking and adjustments]
We expect the best accuracy for the gestational age assessment at birth.