- Medication and Pregnancy KB

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Anderka, 2012	case control	Histories of NVP and treatments obtained from a standardized computer- assisted telephone interview with the mother. Data were collected by month for the first trimester and by trimester for the second and third trimesters.	Case infants (over 30 different birth defects) are identified prenatally, at birth or during the first year of life from surveillance systems (10 participating states). 9 sites also collected fetal deaths at 20 GW or greater and 8 sites collected diagnosed and electively terminated.	Potential confounders for the adjusted analyses were selected a priori: maternal age, race-ethnicity, education, parity, smoking in the month before conception through the first trimester, plurality, previous miscarriage, infant sex, use of folic acid, body mass index (BMI), study site, and year of expected date of delivery.
Ashkenazi-Hoffnung, 2013	prospective cohort	At the initial phone conversation, information was obtained using a standard questionnaire and included use of medications.	The mothers were contacted up to 2 years after the initial phone conversation for a follow-up telephone interview using a structured questionnaire (birth weight, fetal growth, congenital birth defects, infant age and development at follow-up ... were recorded).	None
Asker, 2005	population based cohort retrospective	The standard practice in Sweden is that during the first antenatal care visit (usually between weeks 10 and 12), the pregnant woman is interviewed by a midwife. Among the many questions asked is one which refers to drug use since the woman has become pregnant.	Swedish Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Register.	Adjusted for year of birth, maternal age, parity, smoking, and years of involuntary childlessness. Among singleton infants for preterm and low birth weight.
Bérard, 2019	population based cohort propective	The Quebec Prescription Drug Insurance Plan administered by the Régie de l’assurance maladie du Quebec (RAMQ).	MCMs were identified in the Régie de l’assurance maladie du Quebec (RAMQ) and MedEcho databases and defined according to ICD-9 and ICD-10 codes.	Adjustment for diagnosis of NVP during pregnancy, demographic characteristics, exposure to folic acid, maternal comorbidities, use of health services in the year before.
Berkovitch, 2002	prospective cohort	Data were collected at the time of exposure and before pregnancy outcome was known.	All women were called after the expected date of delivery for a follow-up telephone interview to collect all pregnancy outcomes. Whenever a malformation was reported, it was confirmed with the pediatrician taking care of the baby.	Controls were matched (each metoclopramide exposed woman was matched with a control woman in the same center) for maternal age (±2 years), smoking and alcohol consumption habits, factors that may affect intrauterine growth, birth defects, and psychomotor development.
Bsat, 2003	randomized controlled trial	Patients were prospectively randomized into three treatment groups: pyridoxine–metoclopramide, prochlorperazine, or promethazine. Mean gestational age between 7.9 and 8.6 weeks (according regimens).	Not specified.	None. There were no statistically significant differences among the groups when compared for maternal age, gestational age at enrollment, parity, and subsequent hospitalization for nausea or vomiting.
Bylsma-Howell, 1983	randomized controlled trial	Administration in a double-blind way of metoclopramide or placebo in parturient women undergoing elective Caesarian section.	Neonatal drug effects determined using Apgar (by the attending paediatric intensive care nursery) and the NACS neurobehavioural tests (administred by one blinded examiner, at two, four, six and 24 hours of age using the NACS Neurobehavioural test).	None. All patients were comparable as regards to age, weight and gestational age, while none of the patients experienced dyspeptic symptoms other than the oesophageal refluxing commonly encountered in late pregnancy.
Fejzo, 2013	case control	Participants were asked to submit their medical records and complete an online surveyregarding treatment. The majority of participants, both cases and controls, joined the study and began the survey during their pregnancies.	Participants were asked to submit their medical records and complete an online surveyregarding outcomes. The majority of participants, both cases and controls, were automatically prompted to complete the survey on outcome following their due date.	None.
Fejzo, 2015	case control	Participants were asked to submit their medical records and complete an online survey regarding treatment.	Participants were asked to submit their medical records and complete an online survey regarding outcomes. A follow-up survey was administered on the diagnosis of childhood emotional, behavioral, and learning disorders.	Cases and controls were well-matched for mean maternal age, spontaneous labor, delivery method, and use of assisted reproduction. Children of cases and controls were well-matched for gender and age, with the average age between 8 and 9 years old.
Howard, 1973	randomized controlled trial	The subjects were given either metoclopramide 10 mg or sterile water by intramuscular injection on a double-blind random basis at the start of the test, in each case once labour had definitely become established.	Not specified	None
Huybrechts, 2018	retrospective cohort (claims database)	Prescriptions filled on an outpatient basis.	The presence of congenital malformations was defined using algorithms based on inpatient or outpatient diagnoses and procedure codes in the maternal (first month after delivery) or infant (first 3 months after date of birth) record.	Several adjusted analyses considering some or all potential confounders (or proxies) including treatment indication (nausea and vomiting during pregnancy, hyperemesis gravidarum) and associated conditions (weight loss, dehydration, ...), calendar year, state of residence, age, race, multiple gestation, maternal conditions, concomitant medications, and general markers of the burden of illness.
Kafle, 1993	randomized controlled trial	Patients randomly divided into two groups to receive either intrathecal meperidine (and metoclopramide and ranitidine) or lidocaine (and ranitidine).	Neurological deficits were ruled out in all patients before discharge from the hospital, as reported by paediatrician.	No adjustment. Randomisation.
Lind, 2013	case control	The National Birth Defects Prevention Study uses computer-assisted telephone interviews to collect information from women 6 weeks to 24 months after their estimated date of delivery.	Cases are identified through population-based birth defects surveillance from each states. A clinical geneticist classifies eligible cases of hypospadias as isolated.	Adjusted for maternal age, race/ethnicity, education, pre-pregnancy BMI, previous live births, sub-fertility, study site, and year of due date.
Lussos, 1992	randomized controlled trial	Parturients were randomized in a double-blind fashion to receive either 2 ml (10 mg) metoclopramide, or 2 ml normal saline intraveinously.	Neonatal behavioral assessments using the early neonatal neurobehavioral scale were performed between 30 min and 4 hours of life.	No adjustment. Randomisation.
Matok, 2009	retrospective cohort (claims database)	The three databases — one from Clalit Health Services and two from Soroka Medical Center — were encoded and linked to create a registry of medications dispensed during pregnancy.	Data on outcomes with respect to the infants were ascertained from the hospital records of each mother and newborn, which had the same unique number for the hospitalization. Data on therapeutic abortions were manually collected from the registry of the Committee for Termination of Pregnancies.	Adjustement for maternal age, ethnic group, presence or absence of maternal diabetes, maternal smoking status, presence or absence of peripartum fever, and parity. For major and minor congenital malformations, the odds ratios were adjusted for maternal age, ethnic group, presence or absence of maternal diabetes, maternal smoking status, and parity.
McGarry (Control exposed to perphenazine), 1971	randomized controlled trial	Patients were allocated to one of the three regimes in accordance with random sequence tables. When analgesia became necessary, pethidine 100 mg was given by intramuscular injection, together with either metoclopramide 10 mg or perphenazine 5 mg, or normal saline 2 ml by the same route.	Apgar score of the baby at 1 and 5 minutes after delivery.	No adjustment. Randomisation.
McGarry (Unexposed control), 1971	randomized controlled trial	Patients were allocated to one of the three regimes in accordance with random sequence tables. When analgesia became necessary, pethidine 100 mg was given by intramuscular injection, together with either metoclopramide 10 mg or perphenazine 5 mg, or normal saline 2 ml by the same route.	Apgar score of the baby at 1 and 5 minutes after delivery.	No adjustment. Randomisation.
Neri, 2005	randomized controlled trial	Randomisation by computer. In the metoclopramide group, the patients received metoclopramide infusion (20 mg/500 mL saline for 60 min) at hospital, twice a week for 2 weeks. Oral supplementation with vitamin B12 complex (pyridoxine, hydroxycobalamine) (30 mg/day) prescribed at home.	Not specified	No adjustment. Randomisation.
Orr, 1993	randomized controlled trial	Exposed pregnant women were given metoclopramide 10 mg intramuscularly at least 20 min before induction of anaesthesia.	The babies were examined at birth by a neonatologist and Apgar scores were given at 1 and 5 min. They were also evaluated using a neurobehavioural and adaptive capacity scoring system (NACS) and their general well- being was assessed daily until they were discharged from hospital.	None
Pasternak, 2013	population based cohort retrospective	Prescriptions for metoclopramide dispensed to women in the cohort identified from the National Prescription Registry, with the timing of exposure defined by the prescription fill date.	National Patient Register (malformations and spontaneous births) and Medical Birth Register (stillbirth, preterm birth, low birth weight and small for gestational age).	The 2 groups were matched (1:4 ratio) on the basis of age, calendar year, and propensity scores, which accounted for baseline characteristics at pregnancy onset, and multivariate adjustment, which controlled for exposures occurring during pregnancy.
Shahriari, 2009	randomized controlled trial	Pregnant women were allocated randomly to receive midazolam 2 mg, or metoclopramide 10 mg at the beginning of surgery before skin incision.	Not specified	None
Sorensen, 2000	retrospective cohort (claims database)	Pharmaco-Epidemiological Prescription Database of North Jutland which thus retains key information on all prescribed and reimbursed drugs sold at pharmacies in the county	Danish Medical Birth Registry (general information on all births in Denmark, recorded by midwives and doctors responsible for the deliveries) and Danish Hospital Discharge Registry to assess malformations.	The analysis included the following potential confounders: maternal age, birth order and smoking.
Zarante, 2009	case control	Information collected in 10 Colombian hospitals (NOS).	Information collected in 10 Colombian hospitals (NOS).	No match/adjustment for this group of exposure.

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