Nausea and vomiting in pregnancy – association with pelvic girdle pain during pregnancy and 4-6 months post-partum

MoBa is a prospective population-based pregnancy cohort study conducted by the Norwegian Institute of Public Health [27]. Participants were recruited from all over Norway from 1999 to 2008 and 40.6% of all women that were invited consented to participate. The cohort now includes 114,500 children, 95,200 mothers, and 75,200 fathers. Three questionnaires were answered during pregnancy, with follow-up questionnaires answered post-partum at regular intervals. Pregnancy and birth records from the Medical Birth Registry of Norway (MBRN) were linked to the MoBa cohort [28]. The quality-assured data files entitled ‘version 8’ were used. Response rates for the MoBa version 8 questionnaires can be found elsewhere [29, 30].

The data were primarily collected from four self-administered questionnaires (Q). The first one was answered in gestational week 15 (Q1), and the subsequent questionnaires were administered around week 20 (Q2), week 30 (Q3), and 6 months post-partum (Q4).

Q1 probed into details regarding maternal health and lifestyle, demographics, previous pregnancies, and early first trimester reports of NP, NVP, and PGP.

From Q1 we used maternal height (cm) and weight (kg) at the start of pregnancy to calculate body mass index (BMI, kg/m²), education (seven categories collapsed into: ≤12 years, 13–16 years, or ≥ 17 years), smoking during pregnancy (no, sometimes, or daily), age at menarche (years), incidences of irritability before menses (five categories collapsed into ‘yes/no’), number of previous pregnancies, previous experiences of NVP (yes or no), and experiences of NP, NVP, and PGP in the first 15 weeks of pregnancy (separated into 4 week intervals; yes or no). The incidences of irritability before menses were defined as having reported an alleviation of such symptoms after menses. Years from menarche to pregnancy were calculated by subtracting age at menarche (from Q1) from maternal age at time of birth (from MBRN). Due to obvious erroneous reporting, only values ≥5 years and < 35 years from menarche to current pregnancy were used. Likewise, ages at menarche < 7 years and > 25 years of age were considered to be erroneously reported.

Q2 included a food frequency questionnaire and was answered in mid-pregnancy. Version two of Q2 included detailed questions regarding nausea and vomiting, therefore only women answering this version were included in the sample. While the questions regarding NVP and PGP in Q1 were structured simply as ‘yes/no’ for the corresponding 4 week intervals in early first trimester, the NVP questions in Q2 probed experiences of nausea or vomiting during pregnancy (yes or no), the gestational week of onset and cessation, and whether women were still experiencing nausea and/or vomiting at the time of answering the questionnaire (around gestational week 20). These NP and NVP answers were cross-checked with answers provided in Q1 to avoid inconsistent responses, as detailed in the ‘Study Sample’ section below. Prior to calculating the duration of either nausea or vomiting from variables stating the gestational week of onset and the week of cessation of these conditions, recoding for some variables was required, as described in detail previously [5].

Data from Q3 (gestational week 30) enabled us to differentiate NVP women from women diagnosed with hyperemesis gravidarum (HG), defined as prolonged nausea and vomiting during pregnancy requiring hospitalisation before week 25 of gestation [31]. Q3 also provided comprehensive information regarding pain distribution and pain intensity (none/mild/severe) in the pelvic girdle during pregnancy. We defined PGP as self-reported pain in both the pubic symphysis in the anterior pelvis and bilaterally in the sacroiliac joints in the posterior pelvis (yes or no). Severe PGP (sPGP) was defined as having reported severe pain in all the above pain locations [21]. These conditions are referred to as PGP and sPGP, respectively. We also obtained responses regarding experiences of NP, NVP, and PGP from week 15 to week 29 or more of pregnancy (separated into 4 week intervals; yes or no). All ‘yes/no’ responses for NP, NVP, and PGP from Q1 and Q3 were cross-checked with identified cases based upon the more comprehensive definitions of NP, NVP, and PGP defined above.

We based the reporting of PGP or sPGP during the last part of pregnancy and/or 4-6 months post-partum upon questions in Q4 (six months post-partum) regarding pain in the anterior and bilateral posterior pelvis [32]. Women reporting PGP or sPGP during the last part of pregnancy were added to those women reporting PGP or sPGP in Q3, producing the total number of women reporting PGP or sPGP during pregnancy.

Data concerning maternal age at time of birth (year), parity (primiparous, multiparous), and gestational length (weeks) were obtained from the MBRN. Questions allowing only for an answer of ‘yes’ had non-answers recoded to ‘no’ or ‘none’ from MoBa and MBRN [24].

The entire MoBa cohort includes 114,275 children and 95,200 mothers. The present sample comprises those women deemed eligible for inclusion, having satisfied criteria such as answering relevant questions related to the study in Q1 and version 2 of Q2, being registered in the MBRN with a singleton live birth, with complete weight and height data recorded, with a gestational length between 28 to 42 weeks, and with consistent reports regarding symptoms of NP and NVP throughout the first trimester. Furthermore, as some women participated in MoBa multiple times due to multiple pregnancies, only those women with one participation were included, or else only the first pregnancy if more than one was registered. Women with NP or NVP symptoms were only included if their condition did not develop into HG. A total of 52,678 women fulfilled all these criteria and were included in the study sample. These criteria were identical to those used in our previous studies [5, 24, 33].

The study sample was divided into three groups: symptom-free (SF), nausea alone (NP), and both nausea and vomiting (NVP). Furthermore, we categorised the women according to whether they were with or without all forms of PGP during pregnancy. Two variables were dichotomised according to the median value: nausea duration (< 8 or ≥ 8 weeks) and vomiting duration (< 7 or ≥ 7 weeks). Only women reporting either NP, NVP, or PGP both in the simple ‘yes/no’ questions as well as the more detailed definitions used for these conditions were included in the analyses regarding the reported week of onset.

Descriptive results are presented as means (standard deviations; SDs) or frequencies (%). Comparisons between women with or without PGP, stratified by condition (SF, NP and NVP), were performed by two sample t-test and chi-squared test. PGP and sPGP at 4-6 months post-partum were explored using logistic regression analysis. We present crude and adjusted odds ratios (cOR and aOR, respectively), with 95% confidence intervals (CI). We adjusted for maternal age, BMI, smoking during pregnancy, parity, education, age at menarche, and incidences of irritability before menses after reviewing previous literature regarding NP, NVP, and PGP. Additional adjustment for length of gestation, years from menarche to pregnancy, and use of hormonal contraceptives prior to pregnancy did not change the results, therefore these results are not reported.

A significance level of 0.05 was used except when we studied statistical interaction effects, where 0.01 was used to allow for multiple testing. All analyses were performed using SPSS 22.0 (IBM Corp, Armonk, NY, USA). We followed the guidelines in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement (http://​www.​strobe-statement.​org).

Women with PGP tended to be heavier and with a higher pre-pregnancy BMI compared to those without PGP (Table 1), and the highest means were for NVP women with PGP. Age at menarche and the number of years from menarche to pregnancy were slightly lower for SF, NP, and NVP women with PGP as compared to women without PGP. SF, NP, and NVP women with PGP had the highest proportion with an education ≤12 years, the highest proportion of irritability before menses amongst those primiparous, and the highest proportion with previous experiences of NVP amongst those multiparous, compared to women without PGP.

When the total study sample was compared with women excluded from the sample, similar estimates were seen in regards to age, weight, BMI, and age at menarche, but among the excluded women a lower proportion were primiparous (48.4% vs 52.7%, found in supporting information Additional file 1), had ≤12 years of education (29.2% vs 30.5%), and a higher proportion were daily smokers (5.7 vs 5.1%).

When we studied the timing of onset of total NP and NVP during the specific periods in pregnancy, we observed a sharp increase in early first trimester, with NP peaking in weeks 5-8 (31.9%) and NVP in weeks 9-12 (28.0%, Fig. 1). Thereafter, both conditions decreased steadily. By contrast, among the SF, NP and NVP women, the proportions of PGP increased gradually from 0.3, 1.2 and 1.5%, in weeks 0-4, respectively, to 8.5, 21.5 and 18.2%, respectively, in week 29 or over.

When comparing the occurrences of PGP and sPGP during pregnancy and 4-6 months post-partum with shorter or longer periods of nausea or vomiting, we observed consistently higher proportions of PGP and sPGP for women with longer durations of either nausea or vomiting (Fig. 2).

Analysis of women with PGP and sPGP 4-6 months post-partum showed the NVP group having the highest proportion as compared to the NP and SF groups (Table 2).

Compared to SF women, NP and NVP women had significantly higher odds of PGP 4-6 months post-partum (aOR = 2.14, 95% CI 1.70-2.71, and aOR = 2.83, 95% CI 2.25–3.57, respectively). NVP women also had significantly higher odds of sPGP 4-6 months post-partum (aOR = 3.35, 95% CI 1.78-6.32) while non-significantly increased odds were found among NP women (aOR = 1.87, 95% CI 0.96-3.64).

The strengths of this study are the large sample from a population-based cohort and the linkage to the MBRN, providing detailed access to maternal health during pregnancy. The MoBa cohort specifically addressed NVP-related issues, providing the opportunity to differentiate between NP and NVP women [5, 24, 33]. Likewise, the detailed questions regarding PGP formed a basis for the robust definition of PGP used [21]. As this is a large cohort, numerous significant associations tend to appear, yet the merit of these in the clinical setting are not always relevant. Furthermore, the responses in the MoBa questionnaires do not allow for an easy assessment of the severity of NVP symptoms. Retrospective evaluation of NVP symptoms has previously been reported as a possible source of bias [50]. We attempted to address this by excluding cases with inconsistencies in NVP symptoms reported between questionnaires (n = 15,791) to have as much confidence as possible in the remaining study sample. When we performed sensitivity analyses with the excluded cases included in the sample, the results were mostly unaffected. Women excluded from the present study had similar ages at delivery, BMI and energy intake, while there tended to be more women with a lower education (29.2% vs 30.5%) as well as a higher parity (48.4% vs 52.7%), findings consistent with non-compliance present in other studies [34, 51, 52]. The slightly higher number of daily smokers in the excluded group (5.7% vs 5.1%) is most likely a product of the high number of missing values for this variable. Other weaknesses include the reliance on self-reports of PGP, nausea, and vomiting. The diagnosis of PGP in our study would have benefited from a clinical assessment, as has been suggested elsewhere [13], in order to support the women’s self-reports. However, this is not feasible in a large cohort study. Categorising the difference between retching and actual vomiting (defining NP and NVP) may also have led to misclassifications and affected the results. Another weakness is the lack of information on biomarkers (e.g. hormones).