Trial Outcomes & Findings for Lamotrigine Pregnancy Registry (LAM05) (NCT NCT01064297)

Last Updated: 2013-02-25

Results Overview

The number of live births, fetal deaths, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine monotherapy. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs.

Recruitment status

COMPLETED

Target enrollment

3416 participants

Primary outcome timeframe

Although reports and diagnoses of major congenital malformations are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth

Results posted on

2013-02-25

Participant Flow

Participant milestones

Participant milestones
Measure	Lamotrigine Monotherapy Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine monotherapy at doses between 0-1200 mg/day	Lamotrigine Polytherapy With Valproate Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate, all dose ranges	Lamotrigine Polytherapy Without Valproate Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine polytherapy without valproate, all dose ranges
Overall Study STARTED	2567	219	630
Overall Study COMPLETED	1776	171	497
Overall Study NOT COMPLETED	791	48	133

Reasons for withdrawal

Reasons for withdrawal
Measure	Lamotrigine Monotherapy Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine monotherapy at doses between 0-1200 mg/day	Lamotrigine Polytherapy With Valproate Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate, all dose ranges	Lamotrigine Polytherapy Without Valproate Pregnancy Exposures Prospectively enrolled pregnancies exposed to lamotrigine polytherapy without valproate, all dose ranges
Overall Study Lost to Follow-up	791	48	133

Baseline Characteristics

Lamotrigine Pregnancy Registry (LAM05)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lamotrigine Monotherapy Pregnancy Exposures n=2567 Participants Prospectively enrolled pregnancies exposed to lamotrigine monotherapy at doses between 0-1200 mg/day	Lamotrigine Polytherapy With Valproate Pregnancy Exposures n=219 Participants Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate, all dose ranges	Lamotrigine Polytherapy Without Valproate Pregnancy Exposures n=630 Participants Prospectively enrolled pregnancies exposed to lamotrigine polytherapy without valproate, all dose ranges	Total n=3416 Participants Total of all reporting groups
Age Continuous	27.9 years STANDARD_DEVIATION 5.84 • n=5 Participants	25.8 years STANDARD_DEVIATION 5.49 • n=7 Participants	28.1 years STANDARD_DEVIATION 6.08 • n=5 Participants	27.8 years STANDARD_DEVIATION 5.89 • n=4 Participants
Sex: Female, Male Female	2567 Participants n=5 Participants	219 Participants n=7 Participants	630 Participants n=5 Participants	3416 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Although reports and diagnoses of major congenital malformations are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth

Population: Prospectively enrolled pregnancies exposed to lamotrigine monotherapy.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=1699 Participants The first trimester begins at conception	First Exposure During Second Trimester n=95 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=18 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure n=5 Participants The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Live Birth (Birth Defects Reported)	31 infants	4 infants	1 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Fetal Death (Birth Defects Reported)	1 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Induced Abortion (Birth Defects Reported)	3 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Live Birth (No Birth Defects Reported)	1523 infants	91 infants	17 infants	5 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Fetal Death (No Birth Defects Reported)	10 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Induced Abortion (No Birth Defects Reported)	33 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy Spontaneous Pregnancy Loss	98 infants	0 infants	0 infants	0 infants	—

PRIMARY outcome

Timeframe: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported following assessments made in the delivery room or shortly after birth

Population: Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate.

The number of live births, fetal deaths, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine polytherapy with valproate. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=161 Participants The first trimester begins at conception	First Exposure During Second Trimester n=8 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=3 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure n=1 Participants The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Live Birth (Birth Defects Reported)	14 infants	1 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Fetal Death (Birth Defects Reported)	0 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Induced Abortion (Birth Defects Reported)	2 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Live Birth (No Birth Defects Reported)	134 infants	6 infants	3 infants	1 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Fetal Death (No Birth Defects Reported)	1 infants	1 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Induced Abortion (No Birth Defects Reported)	4 infants	0 infants	0 infants	0 infants	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate Spontaneous Pregnancy Loss	6 infants	0 infants	0 infants	0 infants	—

PRIMARY outcome

Population: Prospectively enrolled pregnancies exposed to the lamotrigine polytherapy without valproate

The number of live births, fetal deaths with pregnancy loss occurring \>=20 weeks gestation, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine polytherapy without valproate. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs. Although birth defects may not have been reported, they cannot be ruled out.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=474 Participants The first trimester begins at conception	First Exposure During Second Trimester n=25 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=3 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Live Birth (Birth Defects Reported)	11 infants	0 infants	1 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Fetal Death (Birth Defects Reported)	0 infants	0 infants	0 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Induced Abortion (Birth Defects Reported)	1 infants	0 infants	0 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Live Birth (No Birth Defects Reported)	418 infants	25 infants	2 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Fetal Death (No Birth Defects Reported)	3 infants	0 infants	0 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Induced Abortion (No Birth Defects Reported)	19 infants	0 infants	0 infants	—	—
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate Spontaneous Pregnancy Loss	22 infants	0 infants	0 infants	—	—

PRIMARY outcome

Timeframe: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth

Population: Among lamotrigine monotherapy exposures: live births, fetal deaths, induced abortions with birth defects, and live births without defects. Due to the likelihood of inconsistent identification of birth defects among spontaneous losses, fetal deaths, and induced abortions without reported birth defects, these offspring were not included in analyses.

Among lamotrigine monotherapy exposures: live births, fetal deaths, induced abortions with birth defects, and live births without defects. Due to the likelihood of inconsistent identification of birth defects among spontaneous losses, fetal deaths, and induced abortions without reported birth defects, these offspring were not included in analyses.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=1558 Participants The first trimester begins at conception	First Exposure During Second Trimester n=95 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=18 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure n=5 Participants The earliest trimester of exposure was not specified	All Trimesters n=1676 Participants Exposure during any trimester of pregnancy
Number of Infants With Major Congenital Malformations by Earliest Trimester of Exposure to Lamotrigine Monotherapy	35 infants	4 infants	1 infants	0 infants	40 infants

PRIMARY outcome

Population: Among lamotrigine polytherapy with valproate exposures: live births, fetal deaths, induced abortions with defects, and live births without defects. Due to the likelihood of inconsistent identification of defects among spontaneous losses, fetal deaths, and induced abortions without reported defects, these offspring were not included in analyses.

The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy with valproate.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=150 Participants The first trimester begins at conception	First Exposure During Second Trimester n=7 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=3 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure n=1 Participants The earliest trimester of exposure was not specified	All Trimesters n=161 Participants Exposure during any trimester of pregnancy
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy With Valproate	14 infants	1 infants	0 infants	0 infants	1 infants

PRIMARY outcome

Population: Among lamotrigine polytherapy without valproate exposures: live births, fetal deaths, induced abortions with defects, and live births without defects. Due to the likelihood of inconsistent identification of defects among spontaneous losses, fetal deaths, and induced abortions without reported defects, these offspring were not included in analyses.

The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy without valproate.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=430 Participants The first trimester begins at conception	First Exposure During Second Trimester n=25 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=3 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure The earliest trimester of exposure was not specified	All Trimesters n=458 Participants Exposure during any trimester of pregnancy
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy Without Valproate	12 infants	0 infants	1 infants	—	13 infants

PRIMARY outcome

Population: Among lamotrigine monotherapy exposures in the first trimester: live births, fetal deaths, induced abortions with defects, and live births without defects. Due to the likely inconsistent identification of defects among spontaneous losses, fetal deaths, and induced abortions without reported defects, these offspring were not included in analyses.

The number of infants with the reported MCM following first trimester lamotrigine monotherapy exposure were counted. Registry personnel contacted the enrolling physician to obtain information on the pregnancy outcome, lamotrigine dosing and duration of exposure, and use of concomitant antiepileptic drugs during pregnancy.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=15 Participants The first trimester begins at conception	First Exposure During Second Trimester n=12 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=6 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure n=2 Participants The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Anencephaly	2 infants	0 infants	1 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Orofacial clefts	2 infants	0 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Hypoplastic left heart/left ventricle hypoplasia	1 infants	0 infants	1 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Transposition of great vessels	2 infants	0 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Ventricular septal defects	0 infants	3 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Minor heart defect, unspecified	0 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Pulmonary stenosis	0 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Hydronephrosis	1 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Renal defect (absent, polysystic, fluid on kidney)	1 infants	0 infants	2 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Cortical dysplasis	0 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Hypospadias	1 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Pyloric stenosis	0 infants	1 infants	0 infants	1 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Diaphragmatic hernia	1 infants	0 infants	1 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Congenital atresia of anus	1 infants	0 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Hip dislocation	1 infants	0 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Club feet	0 infants	1 infants	1 infants	1 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Polydactyly	1 infants	1 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Epidermolysis bullosa	1 infants	0 infants	0 infants	0 infants	—
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received Light spot across entire abdomen	0 infants	1 infants	0 infants	0 infants	—

PRIMARY outcome

Population: Among lamotrigine polytherapy with valproate exposures in the first trimester: live births, fetal deaths, induced abortions with defects, and live births without defects. Due to the likely inconsistent identification of defects among spontaneous losses, fetal deaths, and induced abortions without reported defects, those offspring were excluded.

The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy with valproate were counted.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=13 Participants The first trimester begins at conception	First Exposure During Second Trimester n=3 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Hydrocephalus/spina bifida	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Meningomyelocele	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Orofacial clefts	2 infants	1 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Cardiac septal defects	0 infants	2 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Transposition of great vessels	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Ventricular hypoplasia	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Pulmonary stenosis	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Pyloric stenosis	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Gastroschisis	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Club foot	2 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Polydactyly	1 infants	0 infants	—	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received Microcephaly	1 infants	0 infants	—	—	—

PRIMARY outcome

Population: Among lamotrigine polytherapy without valproate exposures in the first trimester: live births, fetal deaths, induced abortions with defects, and live births without defects. Due to the likely inconsistent identification of defects among spontaneous losses, fetal deaths, and induced abortions without reported defects, those offspring were excluded.

The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy without valproate were counted.

Outcome measures

Outcome measures
Measure	First Exposure During First Trimester n=2 Participants The first trimester begins at conception	First Exposure During Second Trimester n=4 Participants The second trimester begins at 14 weeks gestation	First Exposure During Third Trimester n=6 Participants The third trimester begins at 28 weeks gestation	Unspecified Trimester of Exposure The earliest trimester of exposure was not specified	All Trimesters Exposure during any trimester of pregnancy
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Neural tube defect	0 infants	0 infants	1 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Cardiac septal defect/murmur	0 infants	1 infants	1 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Coarctation of aorta	0 infants	1 infants	0 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Tetralogy of Fallot	0 infants	0 infants	1 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Esophageal defects	0 infants	1 infants	1 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Hypospadias	1 infants	0 infants	0 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Hydroencephalopathy	1 infants	0 infants	0 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Omphalocele	0 infants	1 infants	0 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Extra digit	0 infants	0 infants	1 infants	—	—
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received Skin tags on ear	0 infants	0 infants	1 infants	—	—

Adverse Events

Lamotrigine Monotherapy Pregnancy Exposures

Serious events: 35 serious events

Other events: 0 other events

Deaths: 0 deaths

Lamotrigine Polytherapy With Valproate Pregnancy Exposures

Serious events: 16 serious events

Other events: 0 other events

Deaths: 0 deaths

Lamotrigine Polytherapy Without Valproate Pregnancy Exposures

Serious events: 12 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Lamotrigine Monotherapy Pregnancy Exposures n=1776 participants at risk Prospectively enrolled pregnancies exposed to lamotrigine monotherapy with completed pregnancy outcome (does not include those lost to follow up where outcome information could not be obtained)	Lamotrigine Polytherapy With Valproate Pregnancy Exposures n=171 participants at risk Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate exposures with completed pregnancy outcome (does not include those lost to follow up where outcome information could not be obtained)	Lamotrigine Polytherapy Without Valproate Pregnancy Exposures n=497 participants at risk Prospectively enrolled pregnancies exposed to lamotrigine polytherapy without valproate exposures with completed pregnancy outcome (does not include those lost to follow up where outcome information could not be obtained)
Congenital, familial and genetic disorders Anencephaly	0.17% 3/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Cardiac septal defect/murmur	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	1.2% 2/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.40% 2/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Club foot	0.17% 3/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	1.2% 2/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Coarctation of aorta	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Congenital atresia of anus	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Cortical dysplasis	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Diaphragmatic hernia	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Epidermolysis bullosa	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Esophageal defects	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.40% 2/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Gastroschisis	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hip dislocation	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hydrocephalus/spina bifida	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hydroencephalopathy	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hydronephrosis	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hypoplastic left heart/left ventricle hypoplasia	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Hypospadias	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Light spot across entire abdomen	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Meningomyelocele	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Microcephaly	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Minor heart defect, unspecified	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Neural tube defect	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Omphalocele	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Orofacial clefts	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	1.8% 3/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Polydactyly	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Pulmonary stenosis	0.06% 1/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Pyloric stenosis	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Renal defect (absent, polysystic, fluid on kidney)	0.17% 3/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Skin tags on ear	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Tetralogy of Fallot	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.20% 1/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Transposition of great vessels	0.11% 2/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Ventricular hypoplasia	0.00% 0/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.58% 1/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.
Congenital, familial and genetic disorders Ventricular septal defects	0.17% 3/1776 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/171 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.	0.00% 0/497 This was a prospective enrollment/follow-up study based on exposure/outcome data collected using structured enrollment and birth outcome report forms completed by healthcare providers of pregnant women. This observational study was designed to investigate birth defects, a specific group of serious adverse events (SAEs); no other SAEs were measured.