This prospective cohort study was approved by the Kaiser Permanente Northern California (KPNC) Institutional Review Board and conducted among KPNC’s pregnant members in the San Francisco Bay Area, all of whom provided informed consent. The study was performed in accordance with all relevant guidelines and regulations. KPNC is an integrated health care delivery system whose members comprise 28–30% of the population in the catchment area and have consistently been shown to be representative of the underlying population15,16.

Study population

All pregnant women, aged 18 years or older, and residing in the participating Bay Area counties, were identified through the KPNC electronic medical record (EMR) laboratory database based on positive pregnancy tests. At KPNC, all women suspected to be pregnant were routinely asked to have a pregnancy test done at a KPNC facility. Flyers informing women about the study were posted at the participating facilities and given to women at the time of their pregnancy test. Given that miscarriage can occur very early in pregnancy, recruiting pregnant women as early as possible in their pregnancy was crucial to ensuring as complete ascertainment of miscarriage as possible. Our identification of pregnant women through positive pregnancy lab tests ensured early recruitment. To determine whether a woman’s recurrent miscarriage(s), an indication of higher susceptibility to miscarriage, increases her vulnerability to MF exposure, we oversampled women with two or more prior miscarriages. The pregnant women identified were contacted by a trained recruiter/interviewer to determine their eligibility and willingness to participate in the study. Those who indicated their intention to carry the pregnancy to term and whose gestational age at identification was less than 10 completed weeks (still at risk for miscarriage) were invited to participate in the study. Among 1,627 eligible pregnant women, 1,054 agreed to participate in the study.

Measuring magnetic field exposure during pregnancy

All participating pregnant women were asked to carry an EMDEX Lite meter (Enertech Consultants Inc.) for 24 hours during pregnancy. The EMDEX Lite meter is specifically designed to measure MF, which is measured in milligauss (mG).

To ensure better representation of MF exposure during pregnancy and to apply the knowledge gained from the previous study12, we designed the MF measurement to be conducted on a typical day (a day reflecting participants’ typical pattern of work and leisure activities during pregnancy). In the event that a participant’s daily activities might have been altered from what was originally planned, we also verified with the participants, at the end of the measurement period, whether the measurement day was indeed a typical day of their pregnancy. If not, the measurement day was classified as non-typical.

The EMDEX Lite meter was used to measure MF exposure levels by participating pregnant women from all emitting sources. Participants were also asked to keep a diary during the 24-hour measurement period to allow the researchers to (1) identify locations of daily activities (at home, at home in bed, in transit, at work, and other), (2) verify if activities were reflective of a typical day, and (3) examine if locations and activities were associated with high MF exposure.

MF data together with participants’ diary of activities on the measurement day were examined for quality control, including consistency and potential errors. We excluded 31 subjects who failed to carry the meter as instructed. We also excluded 107 subjects who had incomplete (<90% of their 24-hour measurements) MF measurement data. Those exclusions were made without knowledge of subjects’ pregnancy outcomes.

Previous studies have found that the highest MF levels that pregnant women encounter are the most relevant to miscarriage risk12,13, indicating a possible threshold effect at a given MF level above which developmental embryos may cease to be viable. Thus, this study focused on high levels of MF exposure. We used the 99th percentile of MF measurements during the 24-hour period to classify exposure level, balancing between the need to examine as high of MF level as possible and, at the same time, avoid using less stable indices (e.g., maximum exposure level).

To more accurately reflect participants’ true MF exposure during pregnancy, we made significant efforts to separate those participants whose measurements were conducted during a typical day of their pregnancy from those whose measurements were not conducted on a typical day. Measurements obtained on a typical day are likely more representative of MF exposure during pregnancy while measurements obtained on a non-typical day are more subject to misrepresentation of the true MF exposure level during pregnancy, resulting in misclassifying participants into incorrect MF exposure categories. Such misclassification usually reduces scientists’ ability to detect an underlying association. As demonstrated in a previous study, measurements conducted on a typical day showed a stronger association between MF exposure and miscarriage risk, while measurements conducted on a non-typical day showed virtually no association due to incorrectly classifying participants into MF exposure categories12.

Measurement of miscarriage

Using KPNC EMR data, we were able to identify participants’ pregnancy immediately after a positive pregnancy test, thereby starting follow-up at an earlier gestational age than the first prenatal visit, the earliest time at which most other studies have been able to identify pregnant women. This early follow-up allowed us to ascertain early miscarriages that most other studies would have missed, making it an important strength of this study.

All participants were followed for their pregnancy outcomes from the time of their positive pregnancy test to the end of their pregnancy. In the case of miscarriage, this is, by definition, before 20 completed weeks of gestation. We ascertained pregnancy outcomes through the KPNC EMR databases. For participants whose outcomes were not available in the EMR, we contacted them directly. We were able to identify pregnancy outcomes for all participants except one who had moved out of the area, thus she was excluded from further analysis.

In-person interview

An in-person interview was conducted with all participants to ascertain extensive information on potential confounders, including pregnancy history and risk factors for miscarriage. Previous studies have shown that MF exposure level is seldom related to common socio-demographic characteristics and risk factors12,17,18; thus, the number of potential confounders in this study was small. Nevertheless, we still collected many factors for examination to ensure thorough control of confounders. Two participants were not able to complete the interview, thus they were excluded from the analyses.

The prospective study design also ensured that the in-person interview was blinded to MF exposure for both interviewers and participants, since the EMF measurement was conducted after the interview. This study design enhances the quality of the study findings.

Statistical analysis

We used the Cox Proportional Hazards regression model, with accommodation for left truncation, to examine the association between MF exposure level and miscarriage. Hazard ratios with 95% confidence intervals were used to determine the magnitude and significance of associations. Left truncation arises when study participants enter observation at a point in time (i.e. gestational age at cohort entry) after the time of origin, conception. Participants were followed until either (a) miscarriage, (b) end of pregnancy due to other outcomes (e.g., ectopic pregnancy), at which point they were censored or (c) 20 weeks of gestation, for participants who remained pregnant at that time.

We examined confounders using the change-in-estimate criterion, including the confounder if the miscarriage hazard ratio (HR) for MF changed by 10% or more. While most factors examined were not confounders due to a lack of association with MF exposure, we nevertheless included in the model commonly known risk factors for miscarriage and socio-demographic characteristics.

Given the previous finding that the strength of association between MF and miscarriage varied by whether the MF measurements were taken on a typical or non-typical day12, we first conducted analyses separately by day type. The previous finding was confirmed in the current study, and we therefore conducted the remaining analyses only among those whose MF exposure was measured on a typical day of their pregnancy.

Since we oversampled those with multiple prior miscarriages, we first stratified analysis by those with and without multiple prior miscarriages to determine if the MF association with miscarriage risk differed between these two groups. Once it was determined that the observed associations were largely similar, we included all participants in the analyses and adjusted for prior miscarriage in all the models.

A total of 913 subjects with valid MF measurements and pregnancy outcomes were included in the final analysis.

Statistical analyses were conducted using SAS 9.3.