title: Methylphenidate in Pregnancy: A Multicenter, Prospective, Comparative, Observational Study.
abstract: Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention-deficit disorder with or without hyperactivity (ADD/ADHD). Data on its use in human pregnancy are limited. The primary objective of the study was to evaluate the risk of major congenital anomalies after pregnancy exposure to methylphenidate for medical indications.
  
  
  
  In a prospective, comparative, multicenter observational study performed in 4 participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) between 1996 and 2013, methylphenidate-exposed pregnancies were compared with pregnancies counseled for nonteratogenic exposure (NTE) after matching by maternal age, gestational age, and year at initial contact.
  
  
  
  382 methylphenidate-exposed pregnancies (89.5% in the first trimester) were followed up. The overall rate of major congenital anomalies was similar between the groups (10/309 = 3.2% [methylphenidate] vs 13/358 = 3.6% [NTE], P = .780). The rates of major congenital anomalies (6/247 = 2.4% [methylphenidate] vs 12/358 = 3.4% [NTE], P = .511) and cardiovascular anomalies (2/247 = 0.8% [methylphenidate] vs 3/358 = 0.8% [NTE], P = .970) were also similar after exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period). There was a higher rate of miscarriages and elective terminations of pregnancy in the methylphenidate group. Significant predictors for the miscarriages using Cox proportional hazards model were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23-3.20; P = .005) and past miscarriage (adjusted HR = 1.35; 95% CI, 1.18-1.55; P < .001).
  
  
  
  The present study suggests that methylphenidate does not seem to increase the risk for major malformations. Further studies are required to establish its pregnancy safety and its possible association with miscarriages.
authors.affiliation: The Israeli Teratology Information Service, Israel Ministry of Health, PO Box 1176, Jerusalem, 9446724, Israel. orna.diav-citrin@moh.gov.il.|The Israeli Teratology Information Service, Jerusalem, Israel Ministry of Health.|The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Diav-Citrin
authors.affiliation: The Israeli Teratology Information Service, Jerusalem, Israel Ministry of Health.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Shechtman
authors.affiliation: The Israeli Teratology Information Service, Jerusalem, Israel Ministry of Health.
authors.forename: Judy
authors.initials: J
authors.lastname: Arnon
authors.affiliation: The Israeli Teratology Information Service, Jerusalem, Israel Ministry of Health.
authors.forename: Rebecka
authors.initials: R
authors.lastname: Wajnberg
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Borisch
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Berlin, Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Beck
authors.affiliation: The United Kingdom Teratology Information Service, Newcastle upon Tyne, England.
authors.forename: Jonathan Luke
authors.initials: JL
authors.lastname: Richardson
authors.affiliation: The Motherisk Program, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Pina
authors.initials: P
authors.lastname: Bozzo
authors.affiliation: The Motherisk Program, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Irena
authors.initials: I
authors.lastname: Nulman
authors.affiliation: The Israeli Teratology Information Service, Jerusalem, Israel Ministry of Health.|The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Ornoy
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000028:Abortion, Induced / Q000706:statistics & numerical data*; D000022:Abortion, Spontaneous / Q000453:epidemiology*; D018376:Cardiovascular Abnormalities / Q000139:chemically induced / Q000453:epidemiology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008774:Methylphenidate / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D012306:Risk
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate