Abstract
OBJECTIVE:
To compare maternal and cord blood penicillin concentrations in women with and without obesity who are receiving intrapartum group B streptococcus (GBS) prophylaxis.
METHODS:
We performed a prospective cohort study of term women receiving intrapartum penicillin prophylaxis for GBS colonization (determined by antenatal rectovaginal culture). The following outcomes were compared between obese (body mass index [BMI] 35 or higher at delivery) and nonobese (BMI less than 30 at delivery) groups: penicillin concentration in maternal blood (after two penicillin doses) and umbilical cord blood, GBS rectovaginal colonization status on admission and after two completed doses, and neonatal GBS colonization (using a postnatal ear swab). Fifty-five women were needed to detect a 0.75 SD difference in cord blood penicillin concentrations.
RESULTS:
Fifty-five women were enrolled and had all specimens collected; 49 had complete data for analysis (obese n=25, nonobese n=24). There was no difference in the median maternal penicillin concentration between groups (obese 4.2 micrograms/mL vs nonobese 4.0 micrograms/mL, P=.58). There was, however, a 60% lower median cord blood penicillin concentration in the obese compared with the nonobese group (2.7 micrograms/mL vs 6.7 micrograms/mL, respectively, P<.01), with no significant difference in time from last penicillin dose to delivery (obese 2.9 hours vs nonobese 1.7 hours, P=.07). The difference in cord blood concentrations remained significant after adjustment for nulliparity, hypertensive disorders, and time from last penicillin dose to delivery. Only 59.6% of women tested positive for GBS by rectovaginal culture on admission (obese 60.9% vs nonobese 58.3%, P=.86).
CONCLUSION:
The median cord blood penicillin concentration was 60% lower in neonates born to women with obesity compared with those born to women without obesity. However, all concentrations exceeded the minimum inhibitory concentration. Maternal penicillin levels were not significantly different between groups. More than 40% of women who previously tested positive for GBS by antenatal culture tested negative for GBS on admission for delivery.
Group B streptococcus (GBS) is the leading cause of early-onset neonatal sepsis in the United States.1 In 1996, the Centers for Disease Control and Prevention (CDC) first recommended intrapartum antibiotic prophylaxis for women considered to be at high risk for GBS colonization.2 In 2002, they endorsed routine antenatal screening for GBS colonization in all pregnant women.3 Consequently, rates of neonatal early-onset GBS disease have decreased from 1.8 newborns per 1,000 live births in the 1990s to 0.23 newborns per 1,000 live births in 2015.4 Currently, approximately 10–30% of pregnant women in the United States test positive for GBS colonization in antenatal screening and receive intrapartum antibiotic prophylaxis to reduce the risk of transmission to their neonates.4 Antenatal screening cultures collected within 5 weeks of delivery are considered 87% sensitive and 96% specific for identifying colonization status at delivery.5
Despite the success of these measures, neonatal early-onset GBS disease does still occur. In an analysis of all cases of early-onset GBS disease reported to the CDC Active Bacterial Core surveillance program from 2006 to 2015, 30% of cases occurred in neonates whose mothers had received a CDC-recommended intrapartum antibiotic prophylaxis antibiotic, and 39% of the patients in those cases had documented evidence of at least 4 hours of intrapartum antibiotic prophylaxis before delivery.6 Risk factors that may contribute to neonatal infection despite adequate intrapartum antibiotic prophylaxis warrant further investigation.
It has been shown in other clinical scenarios that higher antibiotic doses are required to achieve adequate therapeutic effects in patients with obesity.7–9 Both pregnancy and obesity can alter the pharmacokinetics and pharmacodynamics of many medications, and β-lactam antibiotics have been shown to have an increased volume of distribution in patients with obesity.10 This increased volume of distribution can lead to diminished therapeutic benefit at the relevant tissue.11 Maternal obesity is a known risk factor for neonatal GBS disease, though this risk has generally been attributed to higher rates of GBS colonization among women with obesity.12–14 However, these data raise the question of whether the recommended intrapartum antibiotic prophylaxis dosing could possibly be inadequate in women with obesity. There are limited data about the pharmacokinetics of penicillin in women in the third trimester of pregnancy, especially in the setting of obesity. No data exist to confirm that the standard dosing of penicillin for intrapartum antibiotic prophylaxis achieves adequate therapeutic concentrations in patients with obesity.
The primary objective of this study was to compare the maternal and cord blood penicillin concentrations achieved in women with and without obesity who are receiving intrapartum antibiotic prophylaxis for GBS colonization. We hypothesized that both maternal and cord blood concentrations would be lower among women with obesity compared with women without obesity. Additionally, an exploratory objective of the study was to assess changes in GBS colonization rates throughout labor.
METHODS
This was a prospective cohort study conducted at the Hospital of the University of Pennsylvania from February 2018 to January 2019. This study was approved by the institutional review board at the University of Pennsylvania. Patients admitted to the labor unit for intended vaginal delivery who met the following criteria were eligible for inclusion: aged 18 years or older with a term (at least 37 weeks of gestation) singleton gestation, tested positive for GBS colonization by rectovaginal culture collected during prenatal care within 5 weeks of enrollment, and documented as positive for GBS colonization in the medical record. The comparison groups included a nonobese group (body mass index [BMI, calculated as weight in kilograms divided by height in meters squared] less than 30) and an obese group (BMI 35 or higher). Of note, a BMI of less than 30 encompasses underweight, normal weight, and overweight BMIs, and a BMI of 35 or higher encompasses women with class II obesity or greater.15 These BMI groups were chosen based on prior literature demonstrating differences in antibiotic concentrations in women with higher-order obesity.7–9 Body mass index was determined by self-reported height and measured weight at the most recent prenatal visit. Body mass index at delivery, as opposed to BMI at the beginning of pregnancy, was used because it was thought to be most relevant to the pharmacologic parameters that may influence penicillin concentrations. Enrolled patients had to receive at least three doses of penicillin to complete collection of all study specimens and be included in final analyses. We excluded the following patients: those receiving intrapartum antibiotic other than penicillin, those who had received antibiotics within 1 week of enrollment, those who had renal impairment (owing to potential differences in drug clearance), and any patient receiving GBS prophylaxis for reasons other than recent positive rectovaginal culture.
Patients were approached in the obstetric unit by study personnel trained in the consenting and study protocol processes. All patients were enrolled before the initiation of penicillin to obtain baseline samples. Study procedures are illustrated in Figure 1. After obtaining written informed consent, the trained study personnel collected an rectovaginal swab for analysis of GBS colonization status on admission, before the initiation of penicillin. All women enrolled in the study then received intravenous penicillin G for intrapartum GBS prophylaxis in accordance with current CDC guidelines: a 5 million–unit dose followed by a 2.5 million–unit dose every 4 hours until delivery.4 Labor management was at the discretion of the patients’ clinicians. Approximately 8 hours later, immediately before the third dose of penicillin, a second rectovaginal swab was collected to analyze for clearance of GBS colonization. A maternal blood sample was also collected at this time for penicillin concentration analysis. This time point was chosen as an attempt to capture the trough level of penicillin after the lower 2.5 million unit dose. Immediately after delivery, a cord blood sample was collected for penicillin concentration analysis. Within one hour of delivery, a swab of the neonate’s external ear was collected for GBS colonization analysis. Women who enrolled in the study but delivered before all study specimens could be collected were excluded from final analyses.
Fig. 1.
Timeline of study specimen collection.
McCoy. Obesity and GBS Prophylaxis. Obstet Gynecol 2020.
After collection, maternal and cord blood specimens were centrifuged at 3000g for 15 minutes and stored in 1-mL aliquots at −80°C. To determine the concentration of penicillin in each sample, 25 microliters of plasma was spiked with 250 picomoles nafcillin as internal standard. Then, plasma protein was precipitated with a mixture of methanol and acetonitrile (1:1). After spinning, clear supernatant was transferred to a 4-mL liquid chromatography–mass spectrometer vial, and the fluid was dried down at room temperature. Then, a mixture of solution A (0.1% of formic acid in water) and methanol (1:1) was added. The liquid chromatography–mass spectrometer technique was used to measure penicillin G using the Agilent 1,200 Infinity LC combined with the Agilent 6410B triple-quad MS system. Samples were injected into liquid chromatography with solution A and solution B (0.1% formic acid in acetonitrile with 0.005% trifluoroacetic acid), with a gradient time of 0 minutes (90% solution A and 10% B), 5 minutes (70%A/30%B), 7 minutes (50%A/50%B), and 8 minutes (2%A/98%B). The flow rate was 0.4 mL/min throughout. The post time was 7 minutes. Retention times with this gradient were 9.5 minutes for penicillin G and 10.3 minutes for internal standard. The precursor product link for penicillin G was 415–199, with fragmentor of 100 V and collision energy 8 V; for nafcillin (internal standard), link was 335–160, with fragmentor 90 V and collision energy 8 V. Polarity mode was positive. The detection limit of this methodologic approach is about 50 picomoles/mL, with a standard error between 10% and 15%.
All women included in the study had tested positive for GBS colonization on antenatal screening by rectovaginal culture collected as part of routine prenatal care by clinicians trained according to CDC guidelines.4 Clinicians at our institution are trained to insert one swab 2 cm into the vagina and then 1 cm into the anus. The two rectovaginal swabs in the study were collected by clinicians or study personnel trained to collect rectovaginal cultures. The two rectovaginal swabs and the one neonatal ear swab were collected using a double swab collection and transport system provided by Cepheid. The swabs were refrigerated at 4°C and then transported at ambient temperature within 24–48 hours to the clinical microbiology laboratory for processing.
The culture was performed as follows: swabs were inoculated into Carrot Broth. The following day, positive Carrot Broths were reported as such and all tubes were subcultured to GBS Detect agar and incubated for 18–24 hours at 35–37°C in 5–10% CO2. After 18–24 hours of incubation, the plates were examined for colonies suspicious for GBS. Any colony with suspicious morphology was identified through VITEK MS to confirm presence or absence of GBS. Swabs were registered as GBS-positive or GBS-negative. The antenatal GBS culture, the intrapartum rectovaginal cultures, and the neonatal cultures were all processed, and results recorded independently. Clinicians and patients were blinded to results of the intrapartum and neonatal swabs.
The primary outcomes were penicillin concentrations in maternal and cord blood. Secondary outcomes included differences in GBS colonization on admission (compared with antenatal GBS-positive culture), need for neonatal sepsis workup, neonatal early-onset GBS disease, maternal chorioamnionitis, and endometritis. Exploratory outcomes included rates of GBS clearance after receiving intrapartum antibiotics and rates of neonatal GBS colonization.
Categorical variables compared using χ2 and Fisher exact tests. Continuous data were assessed for normality with the Shapiro-Wilk test. The t test was used to compare normally distributed data (mean±SD), and the Mann Whitney U test was used to compare nonnormally distributed data (median [interquartile range]). Analyses were adjusted for nulliparity, hypertensive disorders, and time from last penicillin dose to delivery, which were noted to be confounders based on bivariate analysis with P≤.2. Linear regression was used to control for confounders. Analyses were performed using STATA 15.1. Statistical significance was set at P<.05. Our sample size calculation was based on a prior reported average cord blood penicillin concentration of 6.88 micrograms/mL±3.67.16 Assuming a two-sided test, 80% power, and alpha of 0.05, we determined that we would need a total of 55 patients to detect a 0.75 SD difference in cord blood penicillin concentrations, which was thought to represent a clinically relevant difference.
RESULTS
Figure 2 shows the flow diagram of study enrollment. During the study period, 193 eligible patients were screened, and 102 patients consented to the study. There were 55 patients who had complete specimens collected; 13 had delivered before receiving 8 hours of penicillin, 34 had a missed specimen collection due to limitations in research staff availability. After study completion, two patients were found to be ineligible by BMI and were excluded. Ultimately, 49 patients had useable specimens and were included in the final analysis (25 in the obese group and 24 in the nonobese group).
Fig. 2.
Flow diagram depicting study enrollment. BMI, body mass index.
McCoy. Obesity and GBS Prophylaxis. Obstet Gynecol 2020.
Demographic data for study groups are noted in Table 1. The average BMI for women in the obese group was 43.1 compared with 26.4 for those in the nonobese group (P<.01). Eighty percent of patients in the obese group and 58% of patients in the nonobese group were African American (P=.26). The incidences of chronic and pregnancy-related hypertension were noted to be different between groups, with 64% of the obese group compared with 17% of the nonobese group experiencing some form of hypertension (P=.01).
Table 1.
Maternal Demographic and Antepartum Characteristics
| Characteristic | Obese Group (n=25) | Nonobese Group (n=24) | P |
|---|---|---|---|
|
| |||
| BMI at delivery (kg/m2) | 43.166.0 | 26.462.3 | <.01 |
| Insurance type | .38 | ||
| Private | 9 (36) | 12 (50) | |
| Medicaid | 16 (64) | 12 (50) | |
| Age (y) | 28.264.3 | 28.966.2 | .66 |
| Race | .26 | ||
| White | 3 (12) | 6 (25) | |
| African American | 20 (80) | 14 (58) | |
| Other | 2 (8) | 4 (17) | |
| Marital status | .34 | ||
| Single | 19 (76) | 15 (63) | |
| Married | 6 (24) | 8 (33) | |
| Divorced | 0 (0) | 1 (4) | |
| Nulliparous | 7 (28) | 11 (46) | .20 |
| Diabetes | .83 | ||
| Gestational | 3 (12) | 3 (13) | |
| Pregestational | 0 (0) | 1 (4) | |
| Antibiotic use in pregnancy | 3 (12) | 6 (25) | .24 |
| Antibiotic use in 3rd trimester | 1 (4) | 3 (13) | .35 |
| Hypertension | .01 | ||
| Chronic | 4 (16) | 0 (0) | |
| Pregnancy-related | 12 (48) | 4 (17) | |
| UTI in pregnancy | 2 (8) | 4 (17) | .36 |
| Tobacco use during pregnancy | 3 (12) | 3 (13) | .96 |
| Gestational age at delivery | 39.3±1.3 | 39.5±1.4 | .67 |
| Gestational age at GBS swab collection | 36.1±1.1 | 36.0±0.6 | .67 |
BMI, body mass index; UTI, urinary tract infection; GBS, group B streptococcus.
Data are mean±SD or n (%) unless otherwise specified.
Table 2 shows the penicillin concentration results. There was no difference in the median concentration of penicillin in maternal blood between the obese and nonobese groups (4.2 micrograms/mL [3.1–6.7] vs 4.0 micrograms/mL [2.8–5.6], P=.58). The time from last penicillin dose to maternal blood draw was similar between the two groups. There was, however, a significant difference in cord blood penicillin concentrations between groups. In the obese group, the median cord blood penicillin concentration was 60% lower than in the nonobese group (2.7 micrograms/mL [1.0–5.1] vs 6.7 micrograms/mL [5.0–15.1], P<.01). Figure 3 demonstrates the relationships between maternal BMI, and maternal serum and cord blood penicillin concentrations. Although there is no relationship between maternal BMI and maternal serum penicillin concentration, the figure demonstrates the lower cord blood penicillin concentrations with increasing BMI. There was no statistically significant difference in time from last penicillin dose to delivery (obese 2.9 hours [1.7–4.0] vs nonobese 1.7 hours [1.2–3.0], P=.07). Although cord blood penicillin concentrations did decrease with increasing time from the last dose, the regression lines were significantly different between groups (P<.001), demonstrating the significant effect of BMI on this relationship (Fig. 4). Furthermore, a multivariable regression was performed to evaluate all factors with P≤.2 in bivariate analyses, including nulliparity, hypertensive disorders, and time from last penicillin dose to delivery; the final model is shown in Table 3. In this adjusted analysis, the median predicted cord blood penicillin concentrations remain significantly different between groups (obese 3.7 micrograms/mL [2.1–5.2] vs nonobese 11.0 micrograms/mL [9.3–11.7], P<001). to further account for the possible effect of timing of the last penicillin dose on the cord blood concentrations, sensitivity analyses were performed limiting analysis to those who delivered within 2 and 4 hours of their last penicillin dose. In both instances, the median cord blood penicillin concentrations remained significantly different between groups (within 2 hours: obese 5.0 micrograms/mL [2.3–8.4] vs nonobese 12.9 micrograms/mL [7.7–16.3], P=.007; within 4 hours: obese 4.1 micrograms/mL [1.7–6.7] vs nonobese 8.7 micrograms/mL [5.8–15.6], P<.001).
Table 2.
Penicillin Concentration Results
| Result | Obese Group (n=25) | Nonobese Group (n=24) | P |
|---|---|---|---|
|
| |||
| Maternal penicillin concentration (micrograms/mL) | 4.2 (3.1–6.7) | 4.0 (2.8–5.6) | .58 |
| Time from prior penicillin dose to blood draw (h) | 4.0 (3.8–4.4) | 4.1 (3.9–4.2) | .54 |
| Cord blood penicillin concentration (micrograms/mL) | 2.7 (1.0–5.1) | 6.7 (5.0–15.1) | <.01 |
| Cord blood penicillin concentration by quartile (micrograms/mL) | <.01 | ||
| 1 (0.42–2.4) | 11 (46) | 1 (4) | |
| 2 (2.5–5.1) | 7 (29) | 5 (20) | |
| 3 (5.2–8.9) | 4 (17) | 8 (32) | |
| 4 (9–30.46) | 2 (8) | 11 (44) | |
| Time from start of penicillin to delivery (h) | 15.9 (11.3–19.6) | 12.8 (10.7–17.0) | .27 |
| Time from last penicillin dose to delivery (h) | 2.9 (1.7–4.0) | 1.7 (1.2–3.0) | .07 |
| Time from last penicillin dose to delivery by quartile (h) | .31 | ||
| 1 (0.44–1.35) | 4 (16) | 9 (38) | |
| 2 (1.38–2.4) | 6 (24) | 6 (25) | |
| 3 (2.5–3.8) | 7 (28) | 5 (21) | |
| 4 (3.85–9.5) | 8 (32) | 4 (17) | |
| Comparison of cord blood penicillin concentrations by quartile of time from last penicillin dose to delivery (h) | |||
| 1 (0.44–1.35) | 6.0 (2.3–9.5) | 12.9 (6.0–16.0) | .09 |
| 2 (1.38–2.4) | 5.3 (4.8–7.0) | 9.2 (6.7–18.6) | .14 |
| 3 (2.5–3.8) | 1.8 (0.8–4.9) | 5.7 (5.5–6.5) | .06 |
| 4 (3.85–9.5) | 2.1 (0.8–2.8) | 3.3 (1.2–5.0) | .22 |
Data are median (interquartile range) or n (%) unless otherwise specified.
Fig. 3.
Relationship between cord blood penicillin concentration (A) and maternal serum penicillin concentration (B) and maternal body mass index. Dotted line indicates minimum inhibitory concentration.
McCoy. Obesity and GBS Prophylaxis. Obstet Gynecol 2020.
Fig. 4.
Relationship between cord blood penicillin concentration and time from last penicillin dose to delivery by study group, demonstrating a statistically significant difference between regression lines by study group (P<.001).
McCoy. Obesity and GBS Prophylaxis. Obstet Gynecol 2020.
Table 3.
Multivariable Regression Analysis of Cord Blood Penicillin Concentration
| Variable | Unadjusted Coefficient | 95% CI | Adjusted Coefficient* | 95% CI |
|---|---|---|---|---|
|
| ||||
| BMI category (kg/m2) | ||||
| Nonobese (less than 30) | — | — | ||
| Obese (35 or higher) | −6.48 | −9.66 to −3.30 | −5.79 | −8.63 to −2.93 |
| Time from last penicillin dose to delivery (h) | −1.56 | −2.43 to −0.69 | −1.35 | −2.11 to −0.60 |
BMI, body mass index.
Adjusted for BMI category and time from last penicillin dose to delivery.
There were no differences in labor and delivery characteristics or neonatal outcomes between the groups (Appendix 1, available online at http://links.lww.com/AOG/B993). One neonate born to a patient in the nonobese group underwent a sepsis workup; there were no cases of confirmed neonatal sepsis and no neonatal deaths.
Although all women had tested positive for GBS colonization on antenatal rectovaginal screening, in total, only 28 of 49 (59.6%) women tested positive for GBS colonization on rectovaginal culture collected on admission to the labor and delivery unit. This was not different between groups (obese 60.9% vs nonobese 58.3%, P=.86). To examine the rate of GBS clearance in labor, we considered the 28 women who tested positive for GBS colonization on the admission culture. Overall, the rate of clearance of GBS colonization on the second rectovaginal culture, collected after 8 hours of treatment with penicillin, was 68%. At the time of the second rectovaginal culture, nine women remained positive for GBS colonization (four in the obese group and five in the nonobese group, P=.69). When evaluating this subgroup of women with persistence of GBS colonization despite antibiotics, they were not different from the other members of their respective groups in terms of demographic characteristics, clinical outcomes, or maternal or cord blood penicillin concentrations. Three neonates tested positive for GBS colonization on the neonatal ear culture. There was no difference between groups (two [8%] in the obese group and one [4%] in the nonobese group, P=.55). None of these neonates developed GBS sepsis.
DISCUSSION
This prospective cohort study was designed to determine whether the recommended penicillin dosing for GBS intrapartum antibiotic prophylaxis achieves adequate therapeutic concentrations in women with obesity. Although maternal penicillin concentrations were similar, we found that the median cord blood penicillin concentration in women with obesity was nearly 60% lower than in women without obesity. This difference remained significant after adjusted analyses and controlling for timing of penicillin dosing.
Overall, the cord blood penicillin concentrations that we found are consistent with previous literature. Barber et al assessed cord blood penicillin concentrations in laboring women with a mean BMI of 31.6±5.9.16 They did not find a significant association between maternal BMI and cord blood penicillin level; however, they included women with a narrower range of BMIs, as well as mostly White women compared with our majority African American population. Studies in other clinical scenarios have demonstrated significant differences in antibiotic levels achieved in patients with obesity, similar to our findings.7–9 Pevzner et al7 found that among women receiving cefazolin for preoperative prophylaxis before cesarean delivery, women with obesity had significantly lower cefazolin levels in adipose tissue at the start of the surgery. Additionally, several studies have showed altered pharmacokinetics of piperacillin in patients with obesity and the need for higher initial doses to achieve adequate therapeutic effects.8,9,17 The physiologic mechanisms underlying the pronounced difference in cord blood concentrations that we observed, especially in light of the similar maternal serum concentrations, are uncertain. It seems most likely that this is related to differences in volume of distribution and pharmacokinetics at the level of the placenta. Obesity can alter placental function, including elements of lipid metabolism and cytochrome enzyme expression, but it is unknown whether these effects could explain our findings.18,19 Although it is also worth considering whether placental malperfusion in the setting of hypertensive disorders could explain our findings, our results were unchanged when controlling for maternal hypertension.
Whether lower cord blood penicillin concentrations in women with obesity could be a risk factor for GBS disease in their neonates requires further inquiry. Even the lowest cord blood penicillin concentration found in our study (0.42 micrograms/mL) was still above the minimum inhibitory concentration for GBS of 0.12 micrograms/mL. This is consistent with prior studies that demonstrate that cord blood concentrations above minimum inhibitory concentration after 1 million unit doses of penicillin.16,20 In this respect, our data confirm that the penicillin regimen achieves supratherapeutic concentrations in both maternal and cord blood in women with and without obesity. It has been shown, however, that only a small fraction (0.5–2%) of penicillin in the systemic neonatal circulation penetrates the cerebrospinal fluid (Penicillin G potassium injection, USP, https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050638s019lbl.pdf).21 Given that one of the primary neonatal pathologies caused by GBS is meningitis, it is possible that among the lower cord blood penicillin concentrations, the levels in the neonatal cerebrospinal fluid could be subtherapeutic for meningitis prophylaxis. Of note, this study was not adequately powered to assess differences in clinical or infectious outcomes between groups.
Furthermore, our finding that more than 40% of women who tested positive for GBS colonization on antenatal screening then tested negative for GBS colonization at the time of delivery has been shown in other studies that have found rates of 18–30% GBS negativity in the same scenario.22–24 This finding aligns with the recent American College of Obstetricians and Gynecologists recommendation to delay routine antenatal GBS screening to 36 weeks of gestation to reduce discordance between antepartum culture results and intrapartum colonization status.1 The high rate of discordance in our study raises even further concern about women who may change from GBS-negative in prenatal screening to GBS-positive at the time of delivery and are not receiving intrapartum antibiotic prophylaxis. Future work should seek to reduce this discordance, including evaluating the role of point-of-care GBS testing on admission in labor.
The strengths of this study include the prospective design that was powered to examine both maternal and cord blood penicillin concentrations, specifically evaluating the association with obesity. Additionally, our population includes 69% African American women, an often understudied population. Although we were adequately powered for our primary outcomes, our sample size was not large enough to determine differences in rare neonatal outcomes of clinical importance.
Although antenatal screening and intrapartum antibiotic prophylaxis have greatly reduced the rates of early-onset GBS disease, GBS remains the leading cause of infectious morbidity and mortality among term neonates in the United States. Our study demonstrates that there are significant differences in the cord blood penicillin concentrations achieved in women with and without obesity. This finding also has potential implications for other medications that we administer to pregnant women with the goal of achieving a therapeutic effect in the placenta, fetus, or neonate; for instance, administration of ampicillin-sulbactam for treatment of chorioamnionitis. Continued research is needed to better understand optimal medication dosing in pregnant women with obesity, and to ensure that our GBS screening and intrapartum antibiotic prophylaxis protocols are as precise and effective as possible.
Supplementary Material
Acknowledgments
Funding provided by Maternal and Child Health Research Center at the University of Pennsylvania Perelman School of Medicine. Cepheid Inc. donated swabs used for collection of specimens. They had no involvement in the study design, data collection, interpretation, or writing of this manuscript.
The authors thank Y. Daikhin, O. Horyn, and Ilana Nissim for performing the measurements of penicillin at the Metabolomics Core Facility, Children’s Hospital of Philadelphia, as well as the Clinical Microbiology Laboratory staff at the Hospital of the University of Pennsylvania for performing the GBS cultures.
Footnotes
Presented at the Society for Maternal-Fetal Medicine’s 40th Annual Pregnancy Meeting, February 3–8, 2020, Grapevine, Texas.
Each author has confirmed compliance with the journal’s requirements for authorship.
Financial Disclosure
The authors did not report any potential conflicts of interest.
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