Table 3. PhenX measures and protocols in the pregnancy domain.

Measure name*	Protocol sources	Protocol description and rationale
Adequacy of Prenatal Care	Kotelchuck Index, also called the Adequacy of Prenatal Care Utilization (APNCU)	Adequacy of prenatal care is assessed by the month of the initial visit in the pregnancy and total number of prenatal visits until delivery, with that number being calculated as a percentage of recommended visits. Compared to other utilization of care indexes, the Kotelchuck Index is preferred, as it includes a category for women who receive more than the recommended amount of care (adequate plus, or intensive utilization).
Concentrations of Flame Retardants	NCS, Biospecimen Adult Blood Procedures: Standard Operating Procedures NHANES, CDC Laboratory Procedure Manual, PBDEs	Blood samples are collected and analyzed to determine the concentrations of several PBDEs, which are chemicals used as flame retardants. High concentrations of PBDEs in the blood of a pregnant woman or young child may lead to neurobehavioral problems. The NCS was planned as the largest pregnancy cohort studies in the United States, and the NHANES is a major cross-sectional study in the United States. The collection methods used in both been validated previously.
Concentrations of PCBs and Persistent Pesticides	NCS, Biospecimen Adult Blood Procedures: Standard Operating Procedures NHANES, CDC Laboratory Procedure Manual, PCBs and Persistent Pesticides	Blood samples are collected and analyzed to determine the concentrations of several PCBs and persistent pesticides. Prenatal exposure PCBs may lead to poor cognitive function and attention deficit/hyperactivity disorder (ADHD). Prenatal exposures to persistent pesticides (e.g., DDT) may have adverse neurodevelopmental effects on children. The NCS was planned as the largest pregnancy cohort studies in the United States, and the NHANES is a major cross-sectional study in the United States. The collection methods used in both been validated previously.
Concentrations of Phenols and Parabens	NCS Biospecimen Adult Urine Procedures: Standard Operating Procedures NHANES Laboratory Procedure Manual, Bisphenol A, Other Environmental Phenols, and Parabens in Urine	Urine samples are collected and analyzed to determine the concentrations of several phenolic compounds such as bisphenol A (BPA) used to make plastic water bottles, baby bottles, and children's toys. This bioassay also permits analysis of parabens, which are chemicals used as preservatives in foods and beverages, cosmetics, and pharmaceuticals. Some phenols and parabens are endocrine disruptors and some have been associated with adverse health effects. The NCS was planned as the largest pregnancy cohort studies in the United States, and the NHANES is a major cross-sectional study in the United States. The collection methods used in both been validated previously.
Concentration of Trace Metals	NCS Biospecimen Adult Blood Procedures: Standard Operating Procedures NHANES, CDC Laboratory Procedure Manual, Cadmium, Lead, Manganese, Mercury, and Selenium	Blood is collected and analyzed to determine the concentrations of trace metals, which may include cadmium, lead, manganese, selenium, and mercury. High concentrations of metals in the blood may cause neurodevelopmental problems, particularly in a developing fetus or in young children. The NCS was planned as one the largest pregnancy cohort studies in the United States, and the NHANES is a major cross-sectional study in the United States. The collection methods used in both been validated previously.
Current Pregnancy Status	(Self-report) NHANES Reproductive Health Module (Assay) NCS, Biospecimen Adult Urine Procedures: Standard Operating Procedures NHANES Mobile Examination Center Laboratory Procedures Manual	This measure is used to determine whether a woman is currently pregnant. It may be needed to determine suitability for participation in a research study and because pregnancy may influence the results of several physical and health measures such as weight and blood pressure. Depending on specific needs and implications, researchers may accept self-report of pregnancy or require a biological sample (urine or blood) for confirmation. The NHANES question on current pregnancy status was chosen for self-report. However, it was acknowledged that a biological assay is the most accurate pregnancy test and should be used for confirmation if pregnancy determination is critical to the study (i.e., prior to certain investigations such computed tomography, or with the use of pharmaceutical agents). The NCS was planned as the largest pregnancy cohort studies in the United States, and the NHANES is a major cross-sectional study in the United States. The collection methods used in both been validated previously.
Difficulties in Pregnancy	nuMoM2b47 - Difficulties in Pregnancy Visit 1, Form V1E	A measure in the form of a single-item (with 13 subparts) used to capture worries, concerns, and difficulties a woman has experienced related to her pregnancy. Likert-style, self-report questionnaire, administered at 6–13 weeks, and again at 22–29 weeks. The nuMoM2b is a major prospective cohort study collecting data throughout pregnancy on approximately 10,000 nulliparous women. The data collection instruments were developed by the nuMoM2b investigators in collaboration with Project Scientists from the NICHD.
Family History of Pregnancy Complications	nuMoM2b Difficulties in Pregnancy, Maternal Interview Visit 2	Questions to assess a woman's family history of pregnancy complications. Of relevance, as researchers should be knowledgeable about a woman's family history of pregnancy complications, given some complications may be passed from one generation to the next. The nuMoM2b is a major prospective cohort study collecting data throughout pregnancy on approximately 10,000 nulliparous women. The data collection instruments were developed by the nuMoM2b investigators in collaboration with project scientists from NICHD.
Fetal Growth Assessment	Fetal Growth Standards based on NICHD Fetal Growth Studies	This measure includes abstraction of fetal growth and ultrasound information from a medical record. Fetal growth is a gestational age–dependent measure of fetal size, in relation to a defined standard growth curve. Fetal growth at both extremes of pathology (SGA and LGA) affects fetal and neonatal outcomes, and has been linked with a variety of co-morbidities encountered in later life. The Fetal Growth Standards based on NICHD Fetal Growth Studies offer robust methodology and account for ethnic differences in fetal growth. The protocol is accessible and easy to use. The formula chosen to calculate the EFW, which was then used to develop the fetal growth centiles, is well-known and broadly used. Researchers searching for a protocol for fetal growth assessment can apply this formula with ease to calculate the EFW centile for their study, using ultrasound-derived biometry measures, which are then plotted on the available NICHD growth curves.
Gestational Age (GA)	(Maternal Interview) ELGAN Study Maternal Interview (Medical Record Abstraction) GA	For maternal interview, the protocol originates from the well-established ELGAN Project, a large-scale, multi-center, epidemiologic study. Maternal Record Abstraction is the preferred option for establishing GA, with maternal interview provided as an alternate when medical record abstraction is untenable. GA is established using criteria for determination of EDD adapted from ACOG, AIUM, SMFM, and SOGC. Determination of EDD is based on review and correlation of menstrual dating with ultrasound parameters in natural conception and on ART-derived EDD when ART is used.
Gestational Diabetes	nuMoM2b: CLA Prenatal Labs	Abstraction of prenatal laboratory data to determine the presence of gestational diabetes. Pregnant women are commonly screened for gestational diabetes because untreated or poorly controlled gestational diabetes can cause negative health outcomes for the mother and baby, including macrosomia, hypoglycemia, and increased risk for cesarean section delivery. The nuMoM2b is a major prospective cohort study collecting data throughout pregnancy on approximately 10,000 nulliparous women. The data collection instruments were developed by the nuMoM2b investigators in collaboration with the NICHD.
Health and Wellness in Pregnancy	Early Life Exposure Assessment Tool (ELEAT)	The measure is used to determine a woman's general physical and mental health in the time period surrounding her pregnancy. The ELEAT tool has been used in previous studies.
Mode of Conception	(Maternal Interview) PRAMS Phase 7 Core Questions and Standard Questions (Medical Record Abstraction) ELGAN Chart Abstraction Form	Questions assessing whether medical intervention of any kind was needed to achieve pregnancy. Information about natural or assisted conception (i.e., infertility treatments or reproductive technologies) is essential to determine fertility status. Questions for the maternal interview protocol have been derived from PRAMS, a major ongoing survey. Questions for the medical record abstraction protocol have been derived from the ELGAN project, a large, multicenter epidemiologic study.
Mode of Delivery	(Maternal Interview) PRAMS Phase 7 Standard Questions (Medical Record Abstraction) A Randomized Trial of Induction Versus Expectant Management (ARRIVE)	Information about the initiating event of a woman's delivery, the mode of delivery, and if it was an assisted delivery. The mode of delivery may influence the health of both the mother and the neonate. Questions for the maternal interview protocol have been derived from PRAMS, a major ongoing survey.
Prenatal and Postpartum Depression	Edinburgh Postnatal Depression Scale© (EPDS)	This measure is a questionnaire that can be used to screen for recent symptoms of depression, including perinatal and postnatal depression. There are 10 questions to assess a mother's postnatal depression in the previous 7 days. A depression screening tool helps health care providers assess women for symptoms of depression before and after their pregnancy. The EPDS is one of the most widely-used, validated self-report instruments to screen for depression during and after pregnancy.
Supplemental information
Placental Assessment	Amsterdam Placental Workshop Group Consensus Statement & College of American Pathologists Practice Guideline for Examination of the Placenta	A protocol for the histopathologic examination of gross and microscopic placental features. The protocol provides explicit instructions on specimen collection and sampling of placental tissues and guidance on definitions, diagnostic criteria, and classification of placental lesions to assist in international comparability of research studies and continued evolution of knowledge regarding the significance of placental lesions associated with adverse pregnancy and later health outcomes.
International Fetal Growth Standards	Stirnemann J, et al. (2016). International Estimated Fetal Weight Standards of the INTERGROWTH-21st Project. Ultrasound Obstet Gynecol. doi: 10.1002/uog.17347 Hadlock FP, et al. (1985). Estimation of fetal weight using head, body and femur measurements - a prospective study. Am J Obstet Gynecol, 151:333-337.	This measure includes abstraction of fetal growth and ultrasound information from a medical record.

^*All measures and protocols are available at: https://www.phenxtoolkit.org/index.php?pageLink=browse.measures&id=240000 ACOG – American Congress of Obstetricians and Gynecologists; AIUM – American Institute of Ultrasound in Medicine; ART – Assisted Reproductive Technology; BPA – bisphenol A; CDC – Centers for Disease Control; EDD – Estimated Date of Delivery; EFW – Estimated Fetal Weight; ELEAT – Early Life Exposure Assessment Tool; ELGAN – Extremely Low Gestational Age Newborns; GA – Gestational Age; LGA – Large for Gestational Age; NCS – National Children's Study; NHANES – National Health and Nutrition Examination Survey; NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development; nuMoM2b – Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-Be; PBDEs – Polybrominated Diphenyl Ethers; PCBs – polychlorinated biphenyls; PRAMS – Pregnancy Risk Assessment Monitoring System; SGA – Small for Gestational Age; SMFM – Society for Maternal-Fetal Medicine; SOGC – Society of Obstetricians and Gynecologists of Canada