This study examined the prevalence of multiple medication use during pregnancy, factors associated with multiple medication use, as well as associated pregnancy complications. About 35% of pregnant women indicated that they took at least one medication during their pregnancy, and 12% consumed two or more medications during their pregnancy. Women of older age and higher BMI, those born in Australasia and Oceania, higher socioeconomic status, and multimorbidity were more likely to use multiple medications during pregnancy. Women using multiple medications had higher odds of caesarean section, were at higher risk of preterm birth and fetal death, and their newborns had higher rates of admission to SNC/NICU.

In this study, one in three women took at least one medication. The finding is higher than 11.7 in China [33] but in line with a study done in Serbia where rates were 34.7% and 39.2% in Ireland [34, 35]. However, it is higher in many other countries, such as Italy (48%) [36], Sweden (57.6%) [37], and Norway (57.7%) [38], and a broader finding of 60% [39]. The USA reports an even higher rate, with 73.4% of pregnant women taking at least one medication [40]. However, in the USA, only 7.4% of pregnant women were taking two or more medications [14], which is lower than the 12% observed in our population. These variabilities reflect diverse maternal age, BMI, parity, morbidities, healthcare practices, and cultural attitudes towards medication use during pregnancy globally. In addition, the way medication use is extracted, the variation in the included medication, the definition of multiple medication use, differing inclusion and exclusion criteria, the characteristics of pregnant women included vary across studies, and the variability in the year data collected. The field would be advanced by developing more consistent, harmonized, and aligned maternal morbidity, medication reporting systems, and outcome reporting.

In this study, endocrine medications, including insulin, are the most commonly utilized medications during pregnancy, which is in line with other studies [39, 41]. In addition, about 7% of women took antiemetics, similar to other studies [40, 42]. Furthermore, antibiotics, corticosteroids for pregnancy disorders, antihypertensive agents, bronchodilators, and corticosteroids for chronic disorders are also commonly used during pregnancy [40, 40, 43]. Antidepressants were also used by about 3% of women, which is in line with another study [42].

This research identified increasing age, higher BMI, higher IRSD status, and multimorbidity as factors associated with multiple medication use. In Australia, there is a very notable and growing trend of first-time mothers aged over 30 years: 15% before 1981, 23% in 1991, 43% in 2011, and 53% in 2020 [44]. Additionally, the proportion of women with obesity giving birth has risen from 20.7% in 2012 to 24.0% in 2021. Over the same period, the percentage of overweight women giving birth increased from 26.5% to 28.4% [45]. There is clear evidence linking advanced maternal age, overweight, and obesity to an increased prevalence of multiple chronic conditions and obstetric complications [46,47,48,49]. These factors would be expected to cause a rise in pregnant women affected by multimorbidity, including pre-existing conditions, such as hypertension, diabetes mellitus, and asthma, and pregnancy-induced conditions, including pre-eclampsia and gestational diabetes mellitus. Both pre-existing and pregnancy-induced conditions, in turn, contribute to pregnancy complications, adverse outcomes, and higher medication use. The public health consequences of these factors are important to consider and need to be addressed at a population level.

Higher IRSD status was found to be associated with multiple medication use. As high IRSD means that most women are educated and have better occupations and income, it may suggest more well-educated women who are then delaying childbearing for a career and are older with more comorbidities at the time of pregnancy, or it may imply actual inequity in healthcare delivery/access, where women from low IRSD cannot engage with and afford healthcare to be taking multiple medications. However, further research is needed to explore this difference further.

Ethnicity has also been identified as a factor associated with multiple medication use. Australasian and Oceanian women are more likely to use multiple medications as compared with other ethnicities. In addition to a person’s regions of birth, their ancestry, the birthplaces of their parents, and the languages they speak affect their health through various mechanisms [50]. These include social determinants of health, such as socioeconomic status [51,52,53], cultural practices, lifestyle choices, and access to healthcare [54]. Investigations have revealed differences by genetic ancestry for conditions such as diabetes [55, 56] and various cancers [57] associated with an increased risk of these diseases. This genetic variation is thought to explain, at least in part, the disproportionate burden of disease in some populations [57]. This variation in health conditions could lead to variations in medication use. Various studies have also highlighted the differences in multiple medication use rates across geographical locations and ethnic backgrounds. For instance, the New Zealand Māori population demonstrated higher multiple medication use than New Zealand Europeans [58]. Further research is needed to clarify the drivers of differences by regions of birth.

This study also explored the association between multiple medication use and maternal and fetal complications. When adjusted for morbidity, BMI, and maternal age, infants born to mothers taking multiple medications are more likely to require SNC/NICU admission as compared with infants born to mothers who are not taking multiple medications. Moreover, those infants who were born to mothers taking multiple medications have an increased likelihood of preterm birth and fetal death. However, importantly, the association between multiple medication use and outcomes does not equate to causation with likely unmeasured or confounding variables or the possibility of reverse causation. These increased complications are multifactorial, including rising maternal risk factors. Furthermore, women giving birth to preterm infants or infants requiring specialized nursery care are more likely to be prescribed corticosteroids for pregnancy disorders, and other medications meant to support maturing of preterm infants might increase the number of medication use.

The use of specific medications during pregnancy, particularly in the first trimester, is known to lead to adverse effects on the fetus [9, 11, 12], although evidence from randomized controlled trials is scarce owing to significant barriers to including pregnant women in such trials. When multiple medications are used in pregnancy, interactions are even less understood. Medication safety profiles are often assigned based on animal models or studies in the general population (often in male individuals), generating uncertainty around safety during pregnancy and beyond long-term maternal and fetal health [19]. Trials for common medications and post-marketing surveillance for ongoing safety monitoring, particularly in pregnant women, is increasingly important given the demonstrated increase in medication use in pregnancy and could be managed in routine clinical data. This study highlights the need for enhanced monitoring of medication use in pregnant populations to understand the pharmacokinetic and pharmacodynamic profiles better and to ensure the short-term and long-term sequelae are better understood. In addition, pooled individual participant data from large observational studies might increase the strength of evidence for further studies.

Strengths include a large and diverse population across multiple sites and comprehensive capture of pregnancy outcomes. Limitations include potential under-reporting of medications, which can arise from factors such as poor recall, language barriers, or a participant’s choice to withhold certain medication information. In addition, ideally, all medications a woman takes during pregnancy, including supplements, are recorded; however, this process is variable in completeness and inconsistent. Furthermore, as the medication use recording started from the first booking, any medication taken from conception to booking might be missed. While we have identified broad medication classes, the specific medications within these categories often need more detail. The inability to identify specific medications, combinations of multiple medications from the same ‘category’, and the inability to record more than one exposure to a single category of medication is also another limitation. The use of medications such as corticosteroids for fetal lung maturity and magnesium sulfate for neuroprotection are entered into the system to assist with regulatory reporting. However, the medications used intrapartum are not routinely captured on the system used to provide the data extracted in this study. This is the limitation of using routinely collected health data and fragmentation of where health information is stored; however, it also means that the medication data examined in this study are not complicated with other drugs used during the birth. Specifics regarding dosage, timing, frequency, and prescription details are not provided, which constrains deeper analysis. We could also not provide insights into medication patterns based on different pregnancy trimesters and are unable to explore reasons underlying differences by regions of birth. This observational study cannot attribute any of the associations between multiple medications and pregnancy complications as causal. However, it does provide evidence that these associations exist and warrant further investigation within future trials, something which has not been done routinely and yet should be conducted given the large proportion of women taking medications during pregnancy [15].