Escitalopram

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Ames, 2021	case control	Maternal use of SSRIs during pregnancy were ascertained from all participants in three ways: self-report in a telephone interview shortly after study enrollment (SEED Caregiver Interview), self-report on the SEED maternal medical history form, and abstraction from prenatal medical records.	Children completed a multistage process. 1) Mother (mainly) completed the Social Communication Questionnaire. 2) Gold standard clinical assessments: Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales.	Adjusted ORs were adjusted by the following variables: maternal age (continuous), maternal race, maternal education, family income, and smoking history.
Andersen, 2014	population based cohort retrospective	Information on use of prescription medication was collected from the National Prescription Register (the Register of Medicinal Product Statistics), that contains individual-level data on all prescribed drugs dispensed at all pharmacies in Denmark.	The National Hospital Register was used to identified all registered cases of miscarriage (O021 and O03 according to the International Classification of Diseases, 10th Danish Revision) and induced abortion (ICD, 10th Danish Revision codes O04, O05 and O06).	Model adjusted for maternal age, number of previous miscarriages, income, year of outcome or censoring and educational length.
Anderson, 2020	case control	Information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants, conducted 6 weeks to 24 months after the EDD.	Case infants were ascertained through population-based birth-defects surveillance systems in 10 U.S. states. Controls were selected randomly from the same geographic areas. Clinical data were abstracted from medical records and classified by clinician geneticists and other clinicians.	Adjusted for maternal race/ ethnicity, prepregnancy body mass index, education, and early pregnancy smoking and alcohol use
Ban (Controls unexposed, disease free), 2014	retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.	All diagnoses of major congenital anomalies (MCAs) were identified in the children’s medical records using Read codes that we classified into 14 system-specific groups according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroups.	Multivariable analyses were used to adjust for maternal age at the end of pregnancy, year of childbirth, Townsend deprivation quintile, maternal smoking history, body mass index before pregnancy, and maternal diabetes, hypertension, asthma, and epilepsy in the year before conception or during pregnancy.
Ban (Controls unexposed, sick), 2014	retrospective cohort (claims database)	The Health Improvement Network (THIN), a nationally representative database that contains drug prescriptions.	All diagnoses of major congenital anomalies (MCAs) were identified in the children’s medical records using Read codes that we classified into 14 system-specific groups according to the European Surveillance of Congenital Anomalies (EUROCAT) subgroups.	Multivariable analyses were used to adjust for maternal age at the end of pregnancy, year of childbirth, Townsend deprivation quintile, maternal smoking history, body mass index before pregnancy, and maternal diabetes, hypertension, asthma, and epilepsy in the year before conception or during pregnancy.
Chan (Controls exposed to TCA), 2024	retrospective cohort (claims database)	Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.	Diagnoses of malformations were determined by pediatricians, and were ascertained using the ICD-9-CM codes from specialist outpatient and inpatient records.	Exclusion of abnormalities due to maternal infection or exposure to known teratogens. No adjustment for this group of comparison.
Chan (Controls unexposed, pop general), 2024	retrospective cohort (claims database)	Study data were obtained from the Clinical Data Analysis and Reporting System, a database that contains prescribing/dispensing records.	Diagnoses of malformations were determined by pediatricians, and were ascertained using the ICD-9-CM codes from specialist outpatient and inpatient records.	Exclusion of malfo due to maternal infection or exposure to known teratogens. Adjusted for age, parity, maternal pre-existing diseases (diabetes, hypertension, epilepsy...), gestational diabetes, hypertension, placental abnormalities, caesarean delivery, preterm delivery, maternal psychiatric disorders, substance/alcohol use disorders, medications (suspected teratogens, anticonvulsivant ...)...
Colvin, 2012	retrospective cohort (claims database)	The national Pharmaceutical Benefits Scheme (PBS), a claims database that includes 80% of all prescriptions dispensed in Australia.	The Western Australia Data Linkage System (WADLS), which contains data from the Hospital Morbidity Data System, the Midwives’ Notification System, the WA Registry of Births and Deaths and the WA Register of Developmental Anomalies. The ICD-10-AM is used.	None for these outcomes.
Cornet, 2024	retrospective cohort (claims database)	Prescription files of Kaiser Permanente Northern California pharmacies. For each prescription, dispensation date, daily dosage and number of pills dispensed were collected.	Maternal, pregnancy and neonatal data were obtained from electronic medical records of Kaiser Permanente Northern California.	Term infants only. Exclusion of infants with congenital anomalies or genetic abnormalities. Adjusted for maternal age, race/ethnicity, state-subsidized insurance, nulliparity; anxiety or depression during pregnancy, maximal PHQ-9 score, non-SSRI antidepressant/antipsychotic, positive pregnancy toxicology screen, cannabis use; chronic hypertension, type 2 diabetes and infant sex.
Dave, 2019	nested case control	The IBM MarketScan commercial claims database, an employer- sourced health insurance database.	Neonatal abstinence syndrome deliveries were identified using in- and outpatient encounters with the ICD-9 code 779.5 within 30 days of delivery date in either the infant or mother’s medical encounter files.	No adjustment for this substance. Exclusion of any conditions related to iatrogenic Neonatal abstinence syndrome (intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, spontaneous intestinal perforation or bronchopulmonary dysplasia).
Einarson, 2009	prospective cohort	During the initial telephone contact, details of exposure and concurrent exposures are recorded on a standardized questionnaire.	At the follow-up interview, gestational findings, fetal outcomes, and neonatal health are documented on a structured form by telephone interview with each mother. The details are then corroborated with the report of the physician caring for the baby.	The 2 whole groups were matched for maternal age, smoking, and alcohol use. But no matching for individual substance.
Furu, 2015	population based cohort retrospective	The Nordic prescription registers include data on dispensed drugs, substance, brand name, and formulation, together with date of dispensing.	From the medical birth, patient, and malformation registers data on maternal characteristics, the pregnancy and delivery, and major birth defects were retrieved.	Adjusted for maternal age, year of birth, birth order, smoking, maternal diabetes, country, and use of other prescribed drugs (antiepileptics (atC code n03), anxiolytics and hypnotics (n05b and n05C), and angiotensin converting enzyme inhibitors (C09)).
Heuvelman, 2023	retrospective cohort (claims database)	The Clinical Practice Research Datalink (CPRD) contains an extensive code list to identify the name, formulation and dose of medications, which are mandatory fields in the prescription electronic record (according to protocol).	For child outcomes, the primary care clinical and referral records were examined for presence of disorders based on Read codes and for ADHD: prescription of ADHD medication (methylphenidate, dexamphetamine, atomoxetine, dextroamphetamine, amphetamine with dexamphetamine, or lisdexamphetamine).	Adjusted for maternal age, Charlson Comorbidity Index score, maternal disorders (alcohol-related, psychosis, anxiety, self-harm, bipolar disorder, eating disorders, personality disorders, sleep disorders and neuropathic pains), medications (for physical health problems, central nervous system agents, multiple antidepressants ...) smoking, any recorded severity of past depressive symptoms...
Jimenez-Solem (Controls unexposed, NOS), 2012	population based cohort retrospective	The drug redemptions were identified using the Register of Medicinal Product Statistics which has recorded drugs dispensed from Danish pharmacies.	Congenital malformations were identified through the Danish National Hospital Register.	Multivariable logistic regressions are adjusted for mother’s age, parity, income, education, smoking and year of conception.
Jimenez-Solem (Controls unexposed, sick), 2012	population based cohort retrospective	The drug redemptions were identified using the Register of Medicinal Product Statistics which has recorded drugs dispensed from Danish pharmacies.	Congenital malformations were identified through the Danish National Hospital Register.	No adjustment for this group of comparison.
Jordan, 2016	retrospective cohort (registry)	Anomalies registries were linked with prescription and healthcare databases covering their source populations (Danish national Prescription and Patient register; Norway National Prescription Database; and Wales’ health and social care linked electronic databank).	Three congenital anomalies registries that contribute to EUROCAT that routinely collected data on congenital anomalies. Major congenital anomalies were classified according to the EUROCAT standard subgroups (with correspondance with ICD10).	No adjustment for this exposure.
Källén, 2007	population based cohort retrospective	Drug information was obtained from routine midwife interviews at the first antenatal care center visit (in 90% before the end of week 12) using a standardized form.	Congenital malformations were identified from the Swedish Medical Birth Register, from the Register of Congenital Malformations, and from the Hospital Discharge Register.	Adjustments were made for year of birth, maternal age, parity, smoking, and !3 previous miscarriages.
Kieler, 2012	population based cohort retrospective	The prescription registers.	from the medical birth registers and th cause of death registers, infants with persistent pulmonary hypertension of the newborn identified as an ICD-10 code P29.3 or I27.0.	Adjusted for maternal age, dispensed non-steroidal anti-inflammatory drugs and antidiabetes drugs, pre-eclampsia, chronic diseases during pregnancy, country of birth, birth year, level of delivery hospital, and birth order.
Kitchin, 2022	case control	Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians distributed on nine Autonomous Regions (out of 17), which contains prescriptions.	Database for Pharmacoepidemiological Research in Primary Care, a computerized medical longitudinal population database of electronic medical records from 10.153 primary care practitioners and pediatricians, which contains medical diagnoses, medical visits, hospital admissions.	Controls individually matched to cases (maternal age, gestational age, and year of Last Menstrual Period date). Adjusted by number of GP visits, obesity, smoking, HTA, diabetes.
Klieger-Grossmann, 2012	prospective cohort	During the initial telephone contact, details of exposure and concurrent exposures were recorded using a standardized questionnaire. Details regarding the exposure included duration and timing in pregnancy, as well as dose, frequency, and indication for drug use.	After the EDD, researchers telephoned each woman to obtain the outcome of the pregnancy. Then, the researcher sent a letter to the caller’s physician if there were a live birth, asking for verification of the information obtained from the mother regarding the baby’s health.	Controls were matched for maternal age ±2 years, alcohol consumption and smoking, and gestational age at time of call ±2 weeks.
Kolding (Controls unexposed, disease free) , 2021	population based cohort retrospective	Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.	Data on prenatally diagnosed cardiac malformations came from the Danish Fetal Medicine Database and data on cardiac malformations diagnosed up to 1 year postnatally came from the Danish National Patient Registry.	Variables included in the analysis with propensity score fine stratification: ethnicity, civil status, parity, age, BMI, smoking, exposure to teratogens, antihypertensives, antidiabetics, use of other psychotropic drugs, depression diagnosis, diabetes diagnosis.
Kolding (Controls unexposed, sick), 2021	population based cohort retrospective	Exposure to antidepressants was measured using redeemed prescriptions through linkage to the Danish Health Services Prescription Database.	Data on prenatally diagnosed cardiac malformations came from the Danish Fetal Medicine Database and data on cardiac malformations diagnosed up to 1 year postnatally came from the Danish National Patient Registry.	Adjusted for smoking and age at conception.
Laspro, 2024	nested case control	Gestational medication use was identified by medications, prescribed, provider-administered, or reported use by mothers at any point during pregnancy.	Oral cleft cohorts were isolated using a combination of ICD codes, from the EPIC medical records.	None.
Lee (Controls exposed to TCAs), 2025	retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including clinical information like diagnoses, clinic attendances, hospital admissions.	Singleton. No adjustment for this group of comparison.
Lee (Controls unexposed, general pop), 2025	retrospective cohort (claims database)	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including prescribing and dispensing records.	The Clinical Data Analysis and Reporting System (CDARS) that captures and links all clinical data, including clinical information like diagnoses, clinic attendances, hospital admissions.	Singleton. Adjusted for age, parity, maternal diabetes, hypertension, dyslipidaemia, epilepsy, physical comorbidity burden, gestational diabetes and hypertensive disorders, maternal psychiatric disorders, substance/alcohol use disorders, drugs during pregnancy (antipsychotics, lithium, valproate, lamotrigine, carbamazepine, benzodiazepines, z-hypnotics, opioid), history of psychiatric admission...
Liu, 2017	population based cohort retrospective	Information on antidepressant use came from the Danish National Prescription Registry, that covers all prescriptions dispensed in Denmark since 1995.	Information on psychiatric diagnosis came from the Danish Psychiatric Central Research Register, that holds information on all inpatient and outpatient psychiatric treatment in Denmark. Primary outcome was first diagnosis of psychiatric disorders (ICD-10 codes F00-F99) in the offspring.	Adjusted for maternal age, primiparity, maternal psychiatric history, inpatient and outpatient psychiatric treatment from 2 years before pregnancy, dispensing of other psychotropic or antiepileptic during pregnancy, nb of non-psychiatric hospital visits during pregnancy, smoking, place of residence, marital status, highest education, income, year of delivery, and paternal psychiatric history.
Malm, 2011	population based cohort retrospective	The Drug Reimbursement Register that contains data on 98% of reimbursed prescription drug purchases.	The Medical Birth Register and the The Register of Congenital Malformations, which data on diagnoses during pregnancy and delivery and neonatal outcome data (including major malformations). Data are collected from all maternity hospitals and include all births and stillbirths.	Independent variables considered in the adjusted logistic model were maternal age at the end of pregnancy, parity, year of pregnancy ending, marital status, smoking during pregnancy, purchase of other reimbursed psychiatric drugs (including antiepileptics) during the first trimester, and maternal prepregnancy diabetes.
Marks (Controls exposed to Bupropion), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Marks (Controls unexposed, sick), 2021	retrospective cohort	Data were obtained from electronic medical records (EMRs) through the Regenstrief Institute in Indianapolis.	Diagnoses were extracted from the electronic database discharge summaries, delivery records, and/or International Classification of Diseases (ICD) codes. Clinical diagnosis were extracted from the delivery discharge summary written by the clinician caring for the infant.	All results reported as aOR (95% CI) controlling for maternal race, age, insurance, and gestational age at delivery.
Martin, 2024	population based cohort retrospective	In the UK, prescription data were based on the prescriptions written by general practitioners (CPRD GOLD), whereas in Norway and Sweden, dispensation of prescription drugs from all ambulatory pharmacies was used (Norwegian Prescription Database, and Swedish Prescribed Drug Register).	The UK Clinical Practice Research Datalink that contains diagnoses made in primary care and secondary care data; Norway: Medical Birth Registry of Norway and the Norwegian Patient Registry; and Sweden: the Medical Birth Register of Sweden and the National Patient Register.	Singletons only. Adjusted for maternal age at delivery, early-pregnancy body mass index, parity, previous stillbirth, anti-seizure medication and antipsychotic use in the 12 months prior to pregnancy, smoking anytime during pregnancy, maternal depression or anxiety diagnosis prior to the start of pregnancy, proxy measures of socioeconomic position (SEP).
Merlob, 2009	prospective cohort	A standardized pregnancy questionnaire is administered to all women on admittance to the maternity ward and reviewed by the attending neonatologist. The use of any drug during pregnancy is routinely recorded.	Every infant born at the center during that period was examined on the first day of life for cardiac murmur. Those with a persistent murmur on the second or third day of life were examined by a pediatric cardiologist and referred for electrocardiography and echocardiography.	None.
Nordeng - Citalopram/Escitalopram (Controls unexposed, NOS), 2012	cohort	The pregnant women completed 2 questionnaires during pregnancy at around gestational weeks 17 and 30, which included notably questions regarding medication use.	The Medical Birth Registry of Norway (MBRN) which contains detailed medical information and diagnostics regarding the infant originating from mandatory notification forms completed by midwives, obstetricians, and/or pediatricians at delivery and during the hospital stay.	Malfo: adjusted for maternal depression, maternal age at delivery, parity, and use of psychotropic drugs during pregnancy. Preterm, LBW: adjusted for level of depression, maternal age at delivery, education, parity, prepregnancy BMI, maternal asthma or cardiovascular disease, NSAID use, folic acid use, and smoking during pregnancy.
Nordeng - Citalopram/Escitalopram (Controls unexposed, sick), 2012	cohort	The pregnant women completed 2 questionnaires during pregnancy at around gestational weeks 17 and 30, which included notably questions regarding medication use.	The Medical Birth Registry of Norway (MBRN) which contains detailed medical information and diagnostics regarding the infant originating from mandatory notification forms completed by midwives, obstetricians, and/or pediatricians at delivery and during the hospital stay.	No adjustment for this group of comparison.
Ozturk, 2016	prospective cohort	At the first contact, initiated via gynecologists, a detailed patient history form was used to notably record all drug exposures (dose, duration and timing in pregnancy).	Each newborn baby was checked at birth for signs of problems or complications.	None
Palmsten (Controls exposed to TCA), 2013	retrospective cohort (claims database)	Outpatient pharmacy-dispensing data.	Medicaid enrollment information was linked to inpatient and outpatient procedures and diagnoses. Outcome validity was assessed by reviewing delivery hospital medical records for a sample of 183 women. Preeclampsia defined with ICD-9 code for preeclampsia or eclampsia (642.4x–642.7x).	No adjustment for this group of comparison.
Palmsten (Controls unexposed, sick), 2013	retrospective cohort (claims database)	Outpatient pharmacy-dispensing data.	Medicaid enrollment information was linked to inpatient and outpatient procedures and diagnoses. Outcome validity was assessed by reviewing delivery hospital medical records for a sample of 183 women. Preeclampsia defined with ICD-9 code for preeclampsia or eclampsia (642.4x–642.7x).	Adjusted for delivery year, preeclampsia risk factors, depression severity proxies, other antidepressant indications, other medications, and healthcare utilization.
Palmsten b, 2013	retrospective cohort (claims database)	Data of prescription.	Women with an ICD-9 code for 666.x during the admission to hospital for delivery, or within three days after the delivery date, were classified as having postpartum hemorrhage. Atonic postpartum hemorrhage only (666.1x) and inpatient postpartum hemorrhage only, also considered.	Adjusted for delivery year, age, race, multiple pregnancy, diabetes, coagulopathy, number of outpatient and inpatient mood/anxiety disorder diagnoses, other mental health disorder, pain indication, sleep disorder, anticonvulsant, benzodiazepine, aspirin, heparin, low molecular weight heparin and warfarin dispensing, and number of outpatient visits and days in hospital during baseline.
Stephansson, 2013	population based cohort retrospective	The prescription registries in the Nordic countries include data on the dispensed item, substance, brand name, and formulation together with date of dispensing for more than 95% of the total outpatient population.	Information on stillbirth was obtained from the medical birth registries and neonatal and postneonatal deaths were obtained from the Nordic causes of death registries. All diagnoses and causes of death are classified according to the ICD-10 codes.	Adjusted for country and year of birth, maternal age, birth order, smoking in early pregnancy, and maternal diabetes and hypertension.
Viktorin - Citalopram or escitalopram (Controls unexposed, NOS), 2017	population based cohort retrospective	Dispensations identified in the Swedish Prescribed Drug Register that holds information on all dispensed prescription drugs in Sweden.	A clinically ascertained diagnosis of offspring Autism spectrum disorder (ASD) was identified in the Swedish Patient Register, with an ICD-10 code according to: F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9.	Adjusted for birthdate, maternal and paternal age, the father's psychotropic medication overlapping the pregnancy, the mother's one-time dispensations of antidepressant and/or other psychotropic medication that overlapped the pregnancy, for any diagnosis of depression in the mother's lifetime, for any diagnosis of psychiatric disorder subgroups in either the mother and/or father's life time.
Viktorin - Citalopram or escitalopram (Controls unexposed, sick), 2017	population based cohort retrospective	Dispensations identified in the Swedish Prescribed Drug Register that holds information on all dispensed prescription drugs in Sweden.	A clinically ascertained diagnosis of offspring Autism spectrum disorder (ASD) was identified in the Swedish Patient Register, with an ICD-10 code according to: F84.0, F84.1, F84.2, F84.3, F84.4, F84.5, F84.8, or F84.9.	Adjusted for birthdate, maternal and paternal age, the father's psychotropic medication overlapping the pregnancy, the mother's one-time dispensations of antidepressant and/or other psychotropic medication that overlapped the pregnancy, for any diagnosis of depression in the mother's lifetime, for any diagnosis of psychiatric disorder subgroups in either the mother and/or father's life time.
Wemakor, 2015	case control	Medication exposure information came from maternal medical/midwifery notes, created prospectively. Other additional data sources include paediatrician records (postnatal), medical geneticist records (postnatal), GP records of mother (prenatal), and maternal interviews (postnatal).	EUROCAT registries collect data using multiple sources of information: maternity, neonatal, and paediatric records; fetal medicine, cytogenetic, pathology, and medical genetics records; paediatric cardiology services; and hospital discharge and child health records. ICD 9 or 10 classification.	Analyses were adjusted for registry in order to adjust for con- founding that may arise if registries differ in both exposure and outcome prevalences.
Yaris, 2005	prospective cohort	Data surveyed by the interviews.	Examinations were made by obstetric ultrasound for the mothers and birth weight and height, gestational age, APGAR scores, congenital malformation and developmental problems for the babies. Periodic checks of all the babies in the neonatal period, were made the first year, and following years.	None for this group of exposure.
Yazdy, 2014	case control	The telephone interview were conducted by trained nurses within 1 year after delivery. It consisted in questions notably on illnesses and medications. If a mother reported using any medications, the timing and indication for use were noted.	Diagnosis of structural clubfoot was confirmed primarily by orthopedic records (77%); when medical records were not available, maternal report of 3 or more castings for the clubfoot was used to confirm a true structural clubfoot (23%).	Adjusted for maternal smoking, alcohol use, and body mass index.

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