Mirtazapine

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
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
Chan (Controls exposed to SSRIs), 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 ...)...
Djulus (Controls exposed to other antidepressants), 2006	prospective cohort	During the initial telephone contact with mother, details of exposure and concurrent exposures were recorded on a standardized questionnaire. A specific, detailed questionnaire was sent to each prescribing general practitioner regarding drug history.	Gestational findings and fetal outcomes were documented on a structured form by telephone interview with each mother. That was corroborated with the report of the physician caring for the infant with a specific, detailed questionnaire sent to each prescribing general practitioner.	The 2 comparison groups were matched with the mirtazapine group for maternal age at the time of conception (± 2 years), gestational age at the first contact (± 2 weeks), tobacco use, alcohol consumption, and chronic conditions.
Djulus (Controls unexposed, disease free), 2006	prospective cohort	During the initial telephone contact with mother, details of exposure and concurrent exposures were recorded on a standardized questionnaire. A specific, detailed questionnaire was sent to each prescribing general practitioner regarding drug history.	Gestational findings and fetal outcomes were documented on a structured form by telephone interview with each mother. That was corroborated with the report of the physician caring for the infant with a specific, detailed questionnaire sent to each prescribing general practitioner.	The 2 comparison groups were matched with the mirtazapine group for maternal age at the time of conception (± 2 years), gestational age at the first contact (± 2 weeks), tobacco use, alcohol consumption, and chronic conditions (NOS).
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.	No adjustment/no matching for this group of exposure (the 2 whole groups were matched for maternal age, smoking, and alcohol use).
Gungor (Controls exposed to SSRI), 2019	prospective cohort	Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.	After delivery, the medical records of the baby were recorded.	None
Gungor (Controls unexposed, disease free), 2019	prospective cohort	Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.	After delivery, the medical records of the baby were recorded.	None
Gungor (Controls unexposed, sick), 2019	prospective cohort	Patient pregnant women were followed naturalistically throughout their pregnancy. The psychiatric medication and use of other medications were documented in every individual visit.	After delivery, the medical records of the baby were recorded.	None
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...
Källen, 2013	population based cohort retrospective	The exposure data are either based on midwife interviews from the first antenatal visit (usually during weeks 10–12) or on linkage with a prescribed drug register.	Medical Birth Register (MBR) supplemented with data from the Register of Birth Defects (RCM, previously Register of Congenital Malformations) and from a Hospital Discharge Register (HDR).	Adjustment was made for year of birth, maternal age (5-year class), parity (1–4), smoking in early pregnancy (unknown, none, <10 cigarettes/day, ≥10 cigarettes per day), and BMI (unknown, <18.5, 18.5–24.9, 25–29, 9. 30–34.9, ≥35).
Kieler, 2015	nested case control	The prescription registers include data on dispensed item, substance, brand name, and formulation, together with date of dispensing for over 95% of the total outpatient population.	In the registers the diagnoses and pregnancy complications are classified according to the national version of the International Classification of Diseases (ICD).	Controls were matched with cases by country of residence, calendar year of pregnancy end point, age, and parity. Model 2 also adjusting for use of antidiabetics, antiepileptics, or other teratogenic drugs.
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 SSRI), 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...
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).
Ostenfeld, 2022	population based cohort retrospective	Data on pregnancies ending in live births and stillbirths were collected from The Medical Birth Register. Data on pregnancies with abortive outcome before 22 weeks of gestation were obtained from The National Hospital Register.	Data on filled prescriptions including Anatomical Therapeutic Chemical (ATC) code, date, dosage, and package size of filled prescription were collected from the Register of Medicinal Product Statistics.	The pregnancies were matched based on propensity scores using the greedy nearest neighbor matching algorithm, with covariables: maternal age, income, education level, parity, multiple birth pregnancy, smoking during pregnancy, previous pregnancy with the same outcome, prescription drug use (antidiabetic, antihypertensives, antiepileptics, …), hospital care utilization in past year...
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 a (control exposed to SSRIs), 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 a (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 (age, race/ethnicity, primiparity, diabetes, multifetal gestation, pain-related diagnosis...), 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.
Winterfeld (Controls exposed to SSRI), 2015	prospective cohort	Medication exposure (indication, timing in pregnancy, duration, dose, and concomitant medication) was collected at initial Teratology Information Services (TIS) contact.	After the expected date of delivery, follow-up was achieved through a structured telephone interview and/or mailed questionnaire to the patient and/or her health care professional.	Cases and control subjects were matched by TIS center, year of TIS contact (±2 years), maternal age (±2 years), and gestational age at time of call (±4 weeks).
Winterfeld (Controls unexposed, NOS), 2015	prospective cohort	Medication exposure (indication, timing in pregnancy, duration, dose, and concomitant medication) was collected at initial Teratology Information Services (TIS) contact.	After the expected date of delivery, follow-up was achieved through a structured telephone interview and/or mailed questionnaire to the patient and/or her health care professional.	Cases and control subjects were matched by TIS center, year of TIS contact (±2 years), maternal age (±2 years), and gestational age at time of call (±4 weeks).
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.

master protocol