Keywords antibiotics - infection - pregnancy - breastfeeding
Introduction
Antibiotics are essential for treating bacterial infections and are among the most commonly prescribed drugs worldwide [1 ]. Rational use
of these preparations must be ensured in order to avoid the development of resistance [2 ]
[3 ]. For this purpose, guidelines and the concept of “antibiotic stewardship” are available [4 ]. Some particular features
should be considered when treating pregnant women and breastfeeding mothers with antibiotics [5 ]. For example, certain preparations are
associated with an increased risk of malformations in children [5 ]
[6 ]. In the
literature, changes in the fetal microbiome due to antibiotics and the resulting development of obesity or childhood atopic diseases are also discussed [7 ]
[8 ].
Antibiotic therapies during pregnancy and breastfeeding therefore pose a particular challenge, as the benefits and risks must be weighed appropriately [5 ]
[9 ]
[10 ]
[11 ]
[12 ]
[13 ]. Since randomized controlled trials in pregnant
women are hardly justifiable, the evidence of current treatment guidelines is usually low [5 ]
[14 ]. However, there are some recommendations [5 ]
[15 ] and
guidelines [16 ]
[17 ]
[18 ]
[19 ] for antibiotic treatment in pregnancy and breastfeeding. For Germany, there are hardly any analyses to date on
the use of antibiotics in this critical phase and on the factors influencing their prescription. It is well known that a high level of education [3 ]
[20 ], a high level of health awareness, and a stable socioeconomic environment [3 ]
[20 ]
[21 ] can lead to reduced antibiotic use. However, study
results on this issue are inconsistent [21 ]
[22 ].
The aim of this analysis was to describe potential patterns and determinants of antibiotic treatments during pregnancy and in the first six months after birth using data from the “Healthy
Living in Pregnancy” (GeliS) study [23 ]. The reasons for treatment, the preparations used, and possible influencing factors were also
investigated. Another goal was to compare these results with the existing recommendations.
Methods
Design and setting of the GeliS study
This is a retrospective secondary analysis of the GeliS study. It was designed as a cluster randomized intervention study to investigate whether lifestyle intervention during pregnancy can
prevent excessive weight gain [23 ]. The National Academy of Medicine criteria were used to classify excessive weight gain [24 ]. The participants in the GeliS study were recruited from 71 medical practices in Bavaria as part of routine care [25 ]. The study protocol was approved by the Ethics Committee (project number 5653/13) of the Medical Faculty of the Technical University of
Munich. The GeliS study was registered in the ClinicalTrials.gov Protocol Registration System (NCT01958307).
Study participants
Between 2013 and 2015, 2286 pregnant women were recruited for the GeliS study. The participants were enrolled in the study before 12 weeks of pregnancy, were between 18 and 43 years of age,
and had a body mass index (BMI) ranging from 18.5 to 40.0 kg/m2 . Other selection criteria included sufficient knowledge of the German language and a written declaration of
consent. Women with multiple pregnancies, high-risk pregnancies, such as placenta previa, persistent bleeding, cervical insufficiency, and pregnancy-induced high blood pressure or other
serious diseases were excluded [23 ].
The lifestyle intervention in the GeliS study
The women in the intervention group (IG) received structured lifestyle consultations from previously trained practice staff, such as medical assistants, midwives, and gynecologists, at four
different points in time (12th – 16th week of pregnancy, 16th – 20th week of pregnancy, 30th – 34th week of pregnancy, 6 – 8 weeks postpartum), which were included in routine care during
pregnancy [23 ]. The consultations were based on the recommendation guidelines of the network “Gesund ins Leben – Netzwerk Junge
Familie” [26 ] and covered topics such as healthy nutrition, supplementation, physical activity, and appropriate weight development
during pregnancy and breastfeeding. Participants were also informed about food-related infections, such as toxoplasmosis or listeriosis. At the time of inclusion in the study, the study
participants in the control group (CG) were only given a flyer with general information on a healthy lifestyle during pregnancy [23 ].
Data collection
Information on the participants’ anthropometric, demographic, and socioeconomic characteristics was obtained using a screening survey, which was completed before the 12th week of pregnancy.
Data on treatment with antibiotics during pregnancy and in the first six months postpartum were collected retrospectively on average one year after delivery as part of the ex ante planned
follow-up of the study. For this purpose, a standardized survey was sent to the mothers around the children’s first birthday. In free text fields, the reasons for treatment with antibiotics
and information on the drugs (product name and manufacturer information) were queried, with information on the period of use collected separately (see below). The free text responses to
antibiotic treatments were systematically evaluated for further data processing and summarized into appropriate groups. The preparations used were assigned to the respective antibiotic
class.
The question about the intake period was answered using the following response options:
“In the first trimester”
“In the second trimester”
“In the third trimester”
“In the first six months after birth”
The frequency of antibiotic treatment was determined using the following options:
“Once”
“Twice”
“Three times”
“≥ four times”.
With regard to the breastfeeding behavior of the participants, women who reported breastfeeding their child at least once were referred to as breastfeeding. The precise data collection and
analysis of the breastfeeding data from the GeliS study were described by Hoffmann et al. [27 ]. All data were entered into the central
database of the GeliS study at the Munich Study Center. Prior to final evaluation, the plausibility and quality of the data sets were checked according to established standards.
Data processing and statistical analysis
The analysis is based on the data from all study participants who participated in the 1-year follow-up and provided complete information on antibiotic treatment. The information on
antibiotic therapies was described depending on the treatment reasons and active ingredients used by frequency distributions during pregnancy and in the first six months postpartum. A
possible influence of the intervention on the frequency of treatment was examined using a chi-square test.
Subsequently, the treatment frequencies were analyzed depending on other potential influencing factors. For this purpose, the indication of completed antibiotic treatment was determined as
a target variable. First, we investigated possible differences between the intervention and control groups using generalized estimating equations [28 ]. Various covariates were used, such as educational level, smoking status, partnership, breastfeeding behavior, type of delivery (caesarean section or vaginal birth),
and premature birth (before the 37th week of pregnancy). The model was adjusted for the variables parity, as well as the age and BMI category prior to pregnancy. Logistic regression was
chosen to model the binary target variable antibiotic therapy yes/no (1/0). In order to account for regional differences, the regions were used as a subject variable, which were distributed
over five administrative regions. During cluster randomization in the GeliS study, two regions with similar birth figures and sociodemographic characteristics were selected within each
administrative region (Upper Bavaria, Upper Palatinate, Upper Franconia, Middle Franconia, and Lower Franconia) and randomly defined as either a control or intervention region. IBM SPSS for
Windows (Version 26.0 IBM Corp., Armonk, NY, USA) was used as the statistics program. All coefficients whose P values were below 0.05 were considered statistically significant.
In order to check how well the information on antibiotic therapies corresponded to the currently valid recommendations, the Embryotox Portal of the Pharmacovigilance and Consultation Center
for Embryonic Toxicology at the Charité University Medical Center of Berlin [15 ] was used as a main reference. Indicators of the
quality of treatment were the reasons for treatment, the appropriateness of the preparations, and attention to particularly vulnerable phases during pregnancy. All preparations mentioned by
the study participants were compared with the recommendations in Embryotox [15 ] as well as the currently valid guidelines [16 ]
[17 ]
[18 ]
[19 ] on antibiotic therapy during pregnancy. In addition, recommendations were specifically researched at different times of treatments
during pregnancy and breastfeeding, e.g., during particularly vulnerable phases [14 ] in order to be able to evaluate the treatment
frequencies at different times during pregnancy and postpartum.
Results
Participants and their characteristics
Of the 2286 women included in the GeliS study, information on antibiotic treatment during pregnancy and in the first six months postpartum ([Fig. 1 ]) was available for 71.6% of participants (n = 1636).
Fig. 1
Flow chart on the inclusion of the study participants with information on antibiotic treatments.
The mean age of the women included in the evaluation was 30.5 ± 4.3 (standard deviation) years ([Table 1 ]). The mean BMI and mean weight prior
to pregnancy were 24.3 ± 4.4 kg/m2 and 68.1 ± 13.2 kg. 44.2% of the women had earned university entrance qualification or had a university degree, while the remaining participants
had an intermediate secondary school diploma, lower secondary school diploma or no school diploma. Women who reported antibiotic treatment were more likely to be in the lifestyle
intervention group (p = 0.025), were more likely to live without a partner (p = 0.010), and had premature births (p = 0.02) or caesarean sections (< 0.001) more frequently ([Table 1 ]).
Table 1
Characteristics of the study participants.
Antibiotic treatment
Yes
(n = 352)
No
(n = 1284)
Total
(n = 1636)
P valueb
BMI = body mass index.
a mean value ± standard deviation.
b P value for differences between study participants who were and were not treated with antibiotics, tested using a Kruskal-Wallis test for continuous and a chi-square
test for categorical variables.
Age at study inclusiona
30.3 ± 4.3
30.6 ± 4.3
30.5 ± 4.3
0.343
Weight prior to pregnancy (kg)a
68.2 ± 13.8
68.1 ± 13.1
68.1 ± 13.2
0.697
BMI prior to pregnancy (kg/m2 )a
24.3 ± 4.7
24.3 ± 4.4
24.3 ± 4.4
0.731
BMI category prior to pregnancy [n (%)]
0.797
BMI 18.5–24.9 kg/m2
231/352 (65.6%)
839/1284 (65.3%)
1070/1636 (65.4%)
BMI 25.0–29.9 kg/m2
76/352 (21.6%)
294/1284 (22.9%)
370/1636 (22.6%)
BMI 30.0–40.0 kg/m2
45/352 (12.8%)
151/1284 (11.8%)
196/1636 (11.9%)
Weight gain during pregnancy (kg)a
13.8 ± 5.2
14.1 ± 5.1
14.0 ± 5.1
0.506
Country of birth [n (%)]
0.405
Germany
344/352 (97.7%)
1243/1283 (83.8%)
1587/1635 (97.1%)
Other country of birth
8/352 (0.23%)
40/1283 (3.1%)
48/1635 (2.9%)
Level of education, [n (%)]
0.106
Lower secondary school diploma/no diploma
38/352 (10.8%)
180/1282 (14.0%)
218/1634 (13.3%)
Intermediate secondary school diploma
165/352 (46.9%)
530/1282 (41.3%)
695/1634 (42.5%)
University entrance qualification/university degree
149/352 (42.3%)
573/1282 (44.7%)
722/1634 (44.2%)
Lifestyle intervention received [n (%)]
197/352 (56.0%)
632/1284 (49.2%)
829/1636 (50.7%)
0.025
Living with their partner [n (%)]
333/352 (94.6%)
1246/1280 (97.3%)
1579/1632 (96.8%)
0.010
Primiparous, [n (%)]
220/352 (62.5%)
765/1284 (59.6%)
985/1636 (60.2%)
0.321
Breastfed child [n (%)]
308/350 (88.0%)
1072/1275 (84.1%)
1380/1625 (84.9%)
0.069
Premature birth [n (%)]
34/352 (9.7%)
66/1281 (5.2%)
100/1633 (6.1%)
0.002
Caesarean section [n (%)]
124/352 (35.2%)
331/1282 (25.8%)
455/1634 (27.8%)
< 0.001
Antibiotic therapies during and after pregnancy
In the GeliS study, 21.5% of women reported a treatment with antibiotics at least once during pregnancy or in the first six months postpartum ([Table 2 ]). A total of 352 participants received 463 antibiotic therapies, as a proportion of these women were repeatedly treated with antibiotics for recurring infection.
Single treatments were the most common (n = 267; 16.3%). Two treatments were performed in 64 women (3.9%), and only 20 women (1.2%) received three or more treatments with antibiotics.
Table 2
Frequency of antibiotic treatments during pregnancy and in the first six months postpartum.
Intervention group
(n = 829)
Control group
(n = 807)
Total
(n = 1636)
a The sum of treatments over the observation periods deviates from the total treatments, as data were not available for 12 antibiotic treatments at the time.
b Chi-square test based on yes/no information on antibiotic treatments (yes: at least one treatment).
Treatment with antibioticsa [n (%)]
197/829 (23.8%)
155/807 (19.2%)
352/1636 (21.5%)
First trimester
15/829 (1.8%)
13/807 (1.6%)
28/1636 (1.7%)
Second trimester
51/829 (6.2%)
40/807 (5.0%)
91/1636 (5.6%)
Third trimester
56/829 (6.8%)
50/807 (6.2%)
106/1636 (6.5%)
Six months postpartum
67/829 (8.1%)
48/807 (5.9%)
115/1636 (7.0%)
Child not breastfed
6/127 (4.7%)
4/118 (3.4%)
10/245 (4.1%)
Child breastfed
61/697 (8.8%)
43/683 (6.3%)
104/1380 (7.5%)
IG vs. CGb
Χ2 = 5.03; df = 1; p = 0.025
Frequencies of antibiotic treatment over time
The information on the time of antibiotic therapy shows an increasing frequency of treatment from the onset of pregnancy to the first six months postpartum ([Table 2 ]). Antibiotic treatment occurred in 1.7% of study participants in the first trimester of pregnancy. The relative frequency in the second trimester increased to
5.5%, and in the last trimester it increased to 6.5%. Approximately 7.0% of women were treated with antibiotics in the first six months after birth.
The division of participants into IG and CG showed that pregnant women in the IG were treated with antibiotics significantly more often than in the CG (p = 0.025) ([Table 2 ]).
Reasons for antibiotic treatment
In 427 out of 463 (92.2%) cases of antibiotic treatment, information about the reason for the treatment was provided. The frequency distributions for antibiotic treatment in [Fig. 2 ] refer to data from study participants for whom information on the reasons and associated time was available (n = 410 corresponds to
100%).
Fig. 2
Frequencies, reasons (a ) and active ingredients (b ) of antibiotic treatments during pregnancy and in the first six months postpartum. When interpreting
the illustration, it must be noted that the postpartum period of six months is cumulatively longer than the individual trimesters of pregnancy, and thus the probability of antibiotic
treatment increases.
Urinary tract infections (n = 119; 28.6% of the reasons; 7.3% of all study participants) were stated as the most common reason for the treatment, with 16 mentions (3.9% of the reasons) of
ascending urinary tract infections, mostly pyelonephritis. The occurrence of urinary tract infections was evenly distributed over the different time periods. In 74 cases (18.0% of the
reasons; 4.5% of all study participants), other causes were the second most frequently mentioned treatment category. These included, e.g., other bacterial infections (including chlamydia,
borrelia), perioperative infection prophylaxis, nonspecific increases in inflammatory parameters, or local inflammation. Compared with the first trimester (1.4% of the reasons), their
frequency tripled (second trimester; 4.1%), quadrupled (third trimester; 5.6%) and quintupled (in the first six months postpartum; 6.8%) over time. The third most common were ENT
infections, such as otitis media, sinusitis and tonsillitis (n = 59; 14.4% of the reasons; 3.6% of all study participants). Antibiotic treatments for premature rupture of membranes, wound
healing disorders after a caesarean section, or birth injuries were classified as birth complications (n = 43; 10.5% of the reasons; 2.6% of all study participants). In the first six
months after birth, mastitis (n = 37; 9.0% of the reasons; 2.3% of all study participants) was the most common reason for antibiotic treatment ([Fig. 2 ]
a ).
Active ingredients used
Penicillins, including amoxicillin, ampicillin, as well as cephalosporins, erythromycin, and azithromycin (both from the group of macrolides) have been evaluated as safe active
ingredients in pregnancy and while breastfeeding [5 ]
[15 ]
[29 ]. In contrast, the agents in the group of tetracyclines, aminoglycosides, and fluoroquinolones are considered unsafe [15 ]
[29 ]. In total, only 99 statements on the type of antibiotic preparation could
be obtained (20% of the treatments). In the group of penicillins (n = 58), amoxicillin (n = 39) was mentioned the most frequently, including the combination of amoxicillin and the
beta-lactamase inhibitor clavulanic acid (n = 1; in the first trimester due to a bacterial infection). In second place were prescriptions of cephalosporins, which, like penicillins, belong
to the group of beta-lactam antibiotics (n = 21). In four cases, the information provided related to preparations with less extensive studies, which were subject to a strict risk-benefit
assessment but were also considered safe. These included fosfomycin (n = 3) and clindamycin (n = 1) [15 ].
During pregnancy and postpartum, the proportion of treatments with amoxicillin decreased in favor of other active ingredients ([Fig. 2 ]
b ). In the third trimester and postpartum period, cephalosporins were more frequently mentioned ([Fig. 2 ]
b ). The information on the active ingredients was distributed very unevenly between the various indications due to incomplete answers. Most of the
information on the active ingredients was available for ENT infections, with the beta-lactam antibiotics amoxicillin and penicillin being most frequently mentioned. Amoxicillin was also
frequently used in respiratory or urinary tract infections. In the case of further reasons for administrating antibiotics, no clearly dominant active ingredients could be identified.
A review of the active ingredients mentioned by the study participants ([Fig. 2 ]
b ) using the Embryotox database showed that the
information on the preparations mentioned in our study corresponded to the current general recommendations.
Possible factors influencing antibiotic therapy
[Table 3 ] shows the influence of various factors on the frequency of antibiotic treatments in a multivariable model. With 19.5%, fewer
participants in the CG received treatment with antibiotic preparations than in the IG (24.0%) (p < 0.001; [Table 2 ]). Study participants
without a partner were treated with antibiotics more frequently than those with a partner (p < 0.001). Women who were breastfeeding their children were also treated with antibiotics more
frequently compared to non-breastfeeding participants (22.4% vs. 17.1%; p = 0.008). Mothers who gave birth to their children vaginally (19.5%) received antibiotics less frequently
(p = 0.003) compared to mothers who gave birth by caesarean section (27.8%). Antibiotics were used more frequently in premature births (p = 0.012). There were no significant changes in
treatment rates with regard to level of education or smoking behavior ([Table 3 ]). Other lifestyle factors, such as a healthy diet, recorded
using the Healthy Eating Index (HEI, p = 0.132), a vegetarian diet (p = 0.905) or physical activity (p = 0.465) did not result in any significant changes with regard to the frequency of
antibiotic therapies. In a subgroup analysis, participants with caesarean sections were excluded in order to avoid a possible bias due to perioperative antibiotic surgical prophylaxis. In
this analysis, there was still a significant increase in the rate of treatment with antibiotics in the intervention group (p = 0.025) and in women without a partner (p < 0.001) or who
breastfed their children (p = 0.005), but no longer in women with premature births (p = 0.113). The BMI category, age, and parity of women did not affect antibiotic intake.
Table 3
Possible factors influencing treatment with antibiotics (multivariable model).
n (treatments/participants)
Percentage
Effect size (95% CI)
[Odds Ratio]
P valuea
BMI = body mass index; CI = confidence interval.
a Logistic regression function in a generalized estimating equation (GEE) model adjusted for parity, age, and BMI category prior to pregnancy. P values for
Wald-chi-square test.
b Smoking during pregnancy and/or up to one year postpartum.
c Birth before the 37th completed gestational week
Group affiliation
Control group
155/798
19.5%
Reference
Intervention group
197/820
24.0%
1.32 (1.22–1.42)
< 0.001
Level of education
0.092
Lower secondary school diploma/no diploma
38/214
17.8%
Reference
Intermediate secondary school diploma
156/686
22.7%
1.40 (0.96–2.06)
0.083
University entrance qualification/university degree
149/718
20.8%
1.11 (0.79–1.57)
0.549
Partner
No partner
19/53
35.8%
Reference
Partner
330/1565
21.1%
0.44 (0.27–0.70)
< 0.001
Smoking behavior
Non-smoker
318/1412
22.5%
Reference
Smokerb
34/206
16.5%
0.64 (0.37–1.13)
0.123
Breastfeeding behavior
Child not breastfed
42/245
17.1%
Reference
Child breastfed
308/1373
22.4%
1.52 (1.13–2.04)
0.005
Type of delivery
Vaginal birth
228/1172
19.5%
Reference
Caesarean section
124/446
27.8%
1.61 (1.18–2.21)
0.003
Premature birthc
No
218/1518
14.4%
Reference
Yes
34/100
34.0%
1.94 (1.16–3.26)
0.012
When dividing the analysis period into pregnancy (model a) and the first six months postpartum (model b), there was little change with regard to the influence of the factors lifestyle
advice, living with and without a partner, and smoking behavior ([Table 4 ] in the attachment). With regard to breastfeeding, the power of the
effect (relatively more frequent indication of treatment) was greater compared to the original model ([Table 3 ]), but the variable lost
significance. The variables type of delivery and premature birth were significant depending on how the participants assigned the treatment to the third trimester or the first six months
postpartum ([Table 4 ]).
Discussion
In our study cohort, approximately one in five women was treated with an antibiotic during pregnancy or in the first 6 months after delivery. Overall, the results show a cautious attitude of
the attending physicians with regard to prescribing antibiotics. This refers to the choice of active ingredients and the low use of antibiotic preparations in the first trimester of
pregnancy.
Few studies to date have investigated a trimester-specific frequency of antibiotic treatment during pregnancy [30 ]
[31 ]. Mensah et al. [30 ] reported an increase in antibiotic treatment during pregnancy,
especially in the third trimester (79.0% of treatments) in Ghana. In contrast, in a Danish cohort of 706 pregnant women, Stokholm et al. [31 ] described antibiotic prescription frequencies ranging from 13% in the first trimester to 18% in the third trimester. The data from the GeliS study show that antibiotics
were used rarely (1.7% of respondents), especially in the first trimester of pregnancy. It cannot deduce from our data whether this is a consideration of the treating physicians of the
particularly vulnerable developmental phase of the embryo during the first trimester of pregnancy [5 ]
[31 ]
[32 ]. It is well known that the frequency of certain infections increases during the
course of pregnancy and, accordingly, an increase in the frequency of treatment is plausible [32 ].
The main indication for antibiotic treatment are bacterial infections and infection prophylaxis measures [3 ]. However, there is a high
degree of interindividual variability in the frequency of treatment. While Bookstaver et al. [5 ] reported a treatment prevalence of 20–25%
in pregnancy (based on studies from Finland, Canada, and the Netherlands), a frequency of 65% was found in pregnant women in Ghana [30 ].
The most common reason for antibiotic treatment in the GeliS study was urinary tract infection (7.3% of all study participants). These figures correspond to the frequencies of 2–7% [33 ] or 5–10% [34 ] of urinary tract infections treated with antibiotics during pregnancy
from other studies. Of particular note are infections or asymptomatic colonization with group B streptococci, which should be treated to prevent B streptococci sepsis in newborns [35 ]. According to an analysis by Kwatra et al. [36 ], these have a prevalence of
approximately 19% in Europe. In our study, just under 2% of women reported an infection or colonization with group B streptococci. Since this was self-reported, this information may also be
substantially too low.
For antibiotic therapies of bacterial infections in pregnancy and breastfeeding, the group of penicillins and cephalosporins is considered particularly suitable [29 ]. The antibiotic most commonly used for treatment in the GeliS study was amoxicillin. There are well-established studies for this
broad-spectrum penicillin and it appears to be safe in pregnancy and breastfeeding [37 ]. Furthermore, as recommended for pregnancy [15 ], first and second-generation cephalosporins were used for treatment. Like penicillins, these belong to the group of beta-lactam
antibiotics [5 ]
[38 ]. The remaining antibiotic preparations were ampicillin,
fosfomycin, various macrolides (e.g., erythromycin and azithromycin), and other individual active ingredients that are considered unproblematic or safe in pregnancy and breastfeeding [15 ]. However, with the use of e.g., clavulanic acid, health risks cannot be ruled out [5 ].
The frequency of antibiotic treatment also depends on a number of patient-specific influencing factors, such as level of education, income, age, sociocultural status, or lifestyle habits
[3 ]
[21 ]
[31 ]
[39 ]. In contrast to the studies by Stokholm et al. [31 ] and Mangrio et al. [39 ], which described the influences of level of education, age, parity, and other sociodemographic factors on the frequency of antibiotic
treatment, our study showed only trends but hardly any significant effects. Education, age, smoking status, or parity did not show any significant influence on treatment with antibiotics.
Participants without a partner were significantly more likely to be treated with antibiotics in our study, which could be explained by a lack of social support [39 ]. In contrast, women who were breastfeeding their children received antibiotics more frequently, which is likely to be due to the increased
incidence of breast inflammation as a result of breastfeeding [40 ]. It should be noted that breast inflammation and abscesses were less
frequent in the intervention group than in the control group. This difference could be explained by the more thorough discussion of breastfeeding by the GeliS counselling staff in the
intervention group. In addition, a caesarean section was associated with a significantly increased probability of receiving antibiotics. This can be explained by routine antibiotic prophylaxis
during surgical procedures [41 ]. Antibiotics were also used significantly more frequently with babies born prematurely, which seems
plausible, as surgical deliveries by caesarean section may occur more frequently or the premature birth itself may also be an indication for maternal antibiotic prophylaxis. This was also
confirmed in a subgroup analysis of our study. After excluding caesarean sections, there was no significant increase in the frequency of antibiotic treatment for premature births. In addition,
increasing intrauterine infections or premature rupture of membranes may promote premature births, which is why antibiotics should be administered prophylactically in this context [42 ].
In our analysis, a significant effect of GeliS lifestyle counseling on the probability of antibiotic treatment was also observed. Therefore, various other variables relating to lifestyle,
such as nutritional quality (via the “Healthy Eating Index”), a vegetarian diet, or exercise and sports habits were investigated in order to classify the effect of intervention in as much
detail as possible. However, these factors did not show any significant influence on the use of antibiotics.
The significantly increased frequency of antibiotic treatment in the IG may be due to study participants being more aware of health issues and leading a more health-conscious lifestyle,
associated with more intensive medical consultations. In particular, infection prophylaxis measures were performed more frequently in the intervention group compared to the CG. Thus, intensive
lifestyle counseling does not appear to reduce the frequency of antibiotic treatments contrary to expectations. This finding requires further analysis. Overall, the results of this and other
studies suggest that the current knowledge about the frequency of infections and their antibiotic treatment, as well as relevant influencing factors, is still very limited. At the same time, a
careful risk-benefit assessment remains important in order to adequately treat patients and to avoid excessive use of antibiotics due to the known risks and development of resistant bacterial
strains [3 ].
The sample size of 1636 women surveyed is very helpful in gaining an insight into the regional reality of care. However, there was no systematic survey of a total cohort of pregnant and
breastfeeding women for a specific period of time and in a defined area of care, but rather an open survey that was carried out within a selected study population. Thus, generalization to the
entire population of pregnant women over a cross-regional or national scale is only limited. Another limitation of this analysis is that the data on antibiotic treatment were collected
retrospectively using surveys. Thus, memory bias cannot be ruled out, especially regarding the information on the preparations, but also on antibiotic treatments during the birth. In addition,
these data were exclusively self-reported by the participants, which is likely to further limit the validity of the data. The low mentioning of treatments, especially in the peripartum phase,
e.g., in caesarean sections, indicate underreporting, as according to the guideline, antibiotic prophylaxis should be administered at every caesarean section and also for premature births for
certain indications [41 ]
[42 ]. However, it is unclear how consistently this
recommendation is being implemented. A possible spatial correlation of treatment frequencies due to the cluster structure of the study was factored in by appropriately taking this structure
into account in the context of the generalized estimation equations.
The strengths of this study are the sample size, the analysis of numerous possible influencing factors, and detailed information on antibiotic treatment during pregnancy and in the first six
months postpartum, e.g., about the respective reasons for treatment, prescribed preparations, and the timing and frequency of treatments.
Conclusion
The results of our analysis show that antibiotic treatment is administered during pregnancy and postpartum in approximately one in five women, comparable to the results from other European
countries. The information provided by the study participants on the antibiotic preparations used corresponds to the current treatment recommendations. Individual factors such as
sociodemographic parameters, lifestyle, and pregnancy counseling may well be relevant when antibiotics are used. However, there is still a lack of robust evidence on this issue, so further
studies are required before counseling and treatment of pregnant and breastfeeding women regarding antibiotic therapies can be specifically improved. Based on the experience from our analysis,
it is advisable for future studies to also include the physicians in the data collection. Underreporting during the peripartum phase could also be an indication of a lack of patient
information about antibiotic treatment during and shortly after birth. This is a starting point for improving current medical practice. In addition, the creation of antibiograms, especially in
the case of multiple treatments, can improve the detection of resistant bacterial strains.
Attachment
([Table 4 ])
Table 4
Possible factors influencing treatment with antibiotics (multivariable models).
Pregnancy (model a)
Postpartum (first 6 months) (model b)
n (treatments/participants)
[%]
Effect size (95% CI)
[Odds Ratio]
P valuea
n (treatments/participants)
[%]
Effect size (95% CI)
[Odds Ratio]
P valuea
BMI = body mass index; CI = confidence interval
(a) and (b) The models differ in terms of the time periods included (a: pregnancy, b: first 6 months postpartum) and the variable on breastfeeding behavior.
a Logistic regression function in a generalized estimating equation (GEE) model adjusted for parity, age, and BMI category prior to pregnancy. P values for
Wald-chi-square test.
b Smoking during pregnancy.
c Smoking during pregnancy and/or up to one year postpartum.
d Birth before the 37th completed gestational week.
Group affiliation
Control group
103/804 [12.8]
Reference
48/798 [6.0]
Reference
Intervention group
122/823 [14.8]
1.21 (1.03–1.42)
0.021
67/820 [8.2]
1.38 (1.02–1.87)
0.036
Level of education
0.214
0.003
Lower secondary school diploma/no diploma
29/217 [13.4]
Reference
7/214 [3.3]
Reference
Intermediate secondary school diploma
110/692 [15.9]
1.28 (0.84–1.94)
0.254
53/686 [7.7]
2.20 (1.35–3.61)
0.002
University entrance qualification/university degree
86/718 [12.0]
0.94 (0.69–1.30)
0.717
55/718 [7.7]
2.06 (0.84–5.02)
0.113
Partner
No partner
13/53 [24.5]
Reference
6/53 [11.3]
Reference
Partner
212/1574 [13.5]
0.45 (0.22–0.91)
0.027
109/1565 [7.0]
0.59 (0.34–1.05)
0.073
Smoking behavior
Non-smoker
211/1551 [13.6]
Reference
102/1412 [7.2]
Reference
Smoker
14/76 [18.4]
1.20 (0.80–1.79)
0.382b
13/206 [6.3]
0.87 (0.48–1.58)
0.649c
Breastfeeding behavior
Child not breastfed
–
–
–
10/245 [4.1]
Reference
Child breastfed
–
–
–
104/1373 [7.6]
1.92 (0.89–4.14)
0.098
Type of delivery
Vaginal birth
158/1176 [13.4]
Reference
60/1172 [5.1]
Reference
Caesarean section
67/451 [14.9]
1.09 (0.77–1.54)
0.619
55/446 [12.3]
2.74 (1.77–4.23)
< 0.001
Premature birthd
No
200/1527 [13.1]
Reference
107/1518 [7.0]
Reference
Yes
25/100 [25.0]
2.24 (1.20–4.20)
0.012
8/100 [8.0]
1.04 (0.49–2.19)
0.921
Financial Support
The GeliS study was financed with the help of the Else Kröner-Fresenius Foundation (Bad Homburg), the Else Kröner-Fresenius Center for Nutritional Medicine at the Technical University of
Munich, the Competence Center for Nutrition in Bavaria, the Bavarian State Ministry for Nutrition, Agriculture and Forestry, the Bavarian State Ministry of Health and Care
(“Gesund.Leben.Bayern.” health initiative), and the AOK Bavaria, as well as the DEDIPAC consortium as part of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life”.
Study material (pedometers) was made available by Beurer GmbH (Ulm, Germany).
