Timing and dosage of intrapartum prophylactic penicillin for preventing early-onset group B streptococcal disease: assessing maternal and umbilical cord blood concentration.

OBJECTIVE: Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth in relation to time elapsed from administration to delivery and to the minimal inhibitory concentration (MIC) for GBS. MAIN OUTCOME MEASURES: Penicillin G concentrations in maternal and umbilical cord blood in relation to time and dose from administration to time of delivery. RESULTS: In 44 mother-infant dyads, median maternal penicillin G concentration was 0.2 mg/L (IQR 0-0.8 mg/L; range 0-1.6 mg/L). Median infant penicillin G concentration was 1.2 mg/L (IQR 0.5-5.0 mg/L; range 0-12.7 mg/L). In all infants (N=38) born less than 4 hours after the latest IAP administration, penicillin G concentrations far exceeded MIC (0.125 mg/L), even after short time intervals between IAP administration and birth. The highest plasma concentrations were reached in umbilical cord blood within 1 hour from IAP administration to birth.For 44 mother-infant dyads, maternal concentrations were very low compared with their infants'; particularly, very high concentrations were seen in the 20 infants with only one dose of IAP. CONCLUSION: High concentrations of penicillin G were found in umbilical cord blood of infants born less than 4 hours after IAP administration, well above the MIC for GBS.

Comparatively low rates of COVID-19 in women admitted in labor and their newborns prior to routine vaccination of pregnant women: insights from Denmark.

Background: In a country with a high-test frequency, societal lockdown, and pregnancy leave granted from 28 gestational weeks, we investigated SARS-CoV-2 infection in women admitted in labor and their newborn in the pre-vaccine period.Material and methods: A total of 1042 women admitted for delivery in two Danish hospitals agreed to a plasma sample and nasopharyngeal, vaginal, and rectal swabs and to sampling of umbilical cord blood and a nasopharyngeal swab from their newborn at delivery. Plasma samples from women were examined for SARS-CoV-2 antibodies. If antibodies were detected, or the woman had a positive nasopharyngeal swab upon admission or had a household contact with symptoms consistent with COVID-19, SARS-CoV-2 PCR was performed on plasma and swab samples from mother and child.Results: Seventeen women (1.6%) were seropositive. Half the newborn (n = 9 (53%)) of seropositive mothers were also seropositive. None of the seropositive women or newborns had clinical signs of COVID-19 and all had SARS-CoV-2 PCR negative plasma and swab samples.Conclusion: Adherence to specific national guidelines pertaining to testing, self-imposed isolation, and cautious behaviors among pregnant women likely contributed to the exceptionally low prevalence of both prior and current COVID-19 infections detected at the time of childbirth preceding the routine vaccination of pregnant women in Denmark.

Transplacental transfer of SARS-CoV-2 antibodies: a cohort study.

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR-positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy, or COVID-19 symptoms upon admission (November 2020 through August 2021), were included. Mother and infant were tested by NP swabs at delivery, and maternal and infant (umbilical cord) venous blood samples were collected. We obtained clinical information including previous PCR test results from the medical records. SARS-Cov-2 IgM and quantified IgG antibodies were measured by enzyme-linked immunosorbent assay and transfer ratios of IgG. We detected IgG antibodies in 73 women and 65 cord blood sera and found a strong correlation between SARS-CoV-2 IgG concentrations in maternal and umbilical cord sera (r = 0.9; p < 0.05). Transfer ratio was > 1.0 in 51 out of 73 (69%) infants and > 1.5 in 26 (35%). We found that transfer was proportional to time from a positive SARS-CoV-2 PCR NP swab to delivery (r = 0.5; p < 0.05). Transfer ratios of SARS-CoV-2 antibodies were associated with time from infection to delivery with transfer ratios of more than 1.0 in the majority of seropositive mother-infant dyads.

Invasive group B Streptococcus strains and clinical characteristics in Danish infants from 1999 to 2009.

Background: Group B Streptococcus (GBS) infection in infants may result in both respiratory, cardiovascular, and neurological dysfunction and ultimately death of the infant. Surveillance of GBS strains in infants and their clinical characteristics guide development of effective vaccines and other potential treatments and may have implications for future prognostics and infant care. Therefore, we aimed to study GBS serotypes and clonal complexes (CC) in Danish infants with early onset infection (EOD) (0-6 days of life) and late-onset infection (LOD) (7-89 days of life) and to estimate the association between GBS strain and different clinical outcomes. Methods: We included Danish infants less than 3 months of age with GBS isolates from blood or cerebrospinal fluid between 1999 and 2009. GBS isolates were analyzed by serotyping and multilocus sequence typing with classification of isolates into clonal complexes. Clinical characteristics were obtained by questionnaires completed by tending pediatrician including gestational age, Apgar scores, age at onset, meningitis, symptom severity, treatment duration, and mortality. Symptom severities were reported within neurological symptoms, need for respiratory or circulatory support, and treatment of disseminated intravascular coagulation. Results: A total of 212 GBS isolates were collected with 129 from EOD and 83 from LOD. The dominating GBS strains were III/CC17 (41%), Ia/CC23 (17%), III/CC19 (15%), Ib/CC8-10 (7%), and V/CC1 (6%). Strain Ia/CC23 was mostly found in EOD, while III/CC17 was widespread in LOD, though being the most common in both EOD and LOD. Strain III/CC17 and Ia/CC23 had highest percentage of samples from cerebrospinal fluid (26%), while III/CC19 had the least (8%). Strain III/CC19 had highest mortality with about one fifth of infected infants dying (22%) followed by Ia/CC23 (16%), Ib/CC8-10 (9%), and then III/CC17 (6%). The symptom severity varied between strains, but with no strain consistently resulting in more severe symptoms. Conclusion: Some potential differences in disease severity were observed between the different strains. These findings emphasize the continuous need for multimodal surveillance of infant GBS strains and their clinical characteristics to optimize development of GBS vaccines and other potential treatments.

The serotype distribution of Streptococcus agalactiae (GBS) carriage isolates among pregnant women having risk factors for early-onset GBS disease: a comparative study with GBS causing invasive infections during the same period in Denmark.

BACKGROUND: We describe the serotype distribution of Streptococcus agalactiae (GBS) carriage isolates from women in labor and among GBS isolates causing invasive infections during the same period to see if the distribution of carriage serotypes reflects the GBS serotypes causing invasive diseases including early-onset disease (EOGBS). METHODS: Data on invasive isolates from 2019 including serotype, erythromycin and clindamycin susceptibility was retrieved from the Danish national reference laboratory, Statens Serum Institut. Carriage isolates were collected from women with risk factors for EOGBS enrolled at delivery at the maternity ward at a Danish University Hospital, first half of 2019. RESULTS: Among carriage isolates, the dominant serotype was IX (21 %) followed by serotype III (19 %). The resistance to erythromycin and clindamycin was 21 and 26 %, respectively. Among invasive GBS isolates, no case of EOGBS with serotype IX was detected but the distribution of serotypes were otherwise similar to the GBS carrier strains. The corresponding resistance to erythromycin and clindamycin was 23 and 15 %, respectively. Penicillin resistance was not detected among carriage nor invasive isolates. CONCLUSIONS: The distribution of serotypes among carriage and invasive GBS reflects the assumption that EOGBS occur following transmission of GBS from mother to newborn, with the exception of serotype IX.

Campylobacter, Salmonella, and Yersinia antibodies and pregnancy outcome in Danish women with occupational exposure to animals.

BACKGROUND: The aim of this study was to determine antibody titres against Campylobacter, Salmonella, and Yersinia in a population-based cohort of pregnant women in Denmark in order to evaluate adverse pregnancy outcomes (miscarriage, preterm birth, and small for gestational age) in relation to occupational exposure to animals in women exposed to food producing animals. METHODS: We used data and blood samples from the Danish National Birth Cohort. Serum samples collected during the first trimester from 192 pregnant women who were occupationally exposed to domestic animals and 188 randomly selected unexposed pregnant women were analysed for IgG, IgM, and IgA antibodies against Campylobacter, Salmonella, and Yersinia. Pregnancy outcomes of interest were identified through the Danish National Patient Register. RESULTS: Women with occupational exposure to animals had significantly higher IgG antibody concentrations against Campylobacter, Salmonella, and Yersinia, whereas they had lower concentrations of IgM and IgA antibodies. CONCLUSIONS: Serological markers were not identified as risk factors for adverse pregnancy outcomes, with the exception of elevated concentrations of Salmonella antibodies, which were found to be associated with an increased risk of preterm birth.

No excess risk of adverse pregnancy outcomes among women with serological markers of previous infection with Coxiella burnetii: evidence from the Danish National Birth Cohort.

BACKGROUND: Q fever caused by Coxiella burnetii is transmitted to humans by inhalation of aerosols from animal birth products. Q fever in pregnancy is suspected to be a potential cause of fetal and maternal morbidity and fetal mortality but the pathogenesis is poorly understood, and even in Q fever endemic areas, the magnitude of a potential association is not established.We aimed to examine if presence of antibodies to C. burnetii during pregnancy or seroconversion were associated with adverse pregnancy outcomes. METHODS: The Danish National Birth Cohort collected blood samples and interview data from 100,418 pregnant women (1996-2002). We sampled 397 pregnant women with occupational or domestic exposure to cattle or sheep and a random sample of 459 women with no animal exposure. Outcome measures were spontaneous abortion, preterm birth, birth weight and Small for Gestational Age (SGA).Blood samples collected in pregnancy were screened for antibodies against C. burnetii by enzyme-linked immunosorbent assay (ELISA). Samples positive for IgG or IgM antibodies in the ELISA were confirmed by immunofluorescence antibody test (IFA). RESULTS: Among the 856 women, 169 (19.7%) women were IFA positive; 147 (87%) of these had occupational or domestic contact with livestock (IFA cutoff > =1:128).Two abortions were IFA positive vs. 6 IFA negative (OR: 1.5; 95%CI: 0.3-7.6). Three preterm births were IFA positive vs. 38 IFA negative (OR: 0.4; 95% CI: 0.1-1.1). There was a significant difference in birth weight of 168 g (95% CI: 70-267 g) with IFA positive being heavier, and the risk of being SGA was not increased in the newborns of IFA positive women (OR: 0.4; 95%CI: 0.8-1.0).Most seropositive women were IgG positive indicating previous exposure. Seroconversion during pregnancy was found in 10 women; they all delivered live babies at term, but two were SGA. CONCLUSION: We found no increased risk of adverse pregnancy outcome in women with verified exposure to C. burnetii.To our knowledge, this is the first population-based seroepidemiologic study evaluating pregnancy outcome in women with serologically verified exposure to C. burnetii against a comparable reference group of seronegative women.

Presence of antibodies against Coxiella burnetii and risk of spontaneous abortion: a nested case-control study.

BACKGROUND AND AIMS: Q fever is a bacterial zoonosis caused by infection with Coxiella burnetii. It is well established that Q fever causes fetal loss in small ruminants. The suspicion has been raised that pregnant women may also experience adverse pregnancy outcome when the infection is acquired or reactivated during pregnancy. The purpose of this study was to assess the potential association between serologic markers of infection with C. burnetii and spontaneous abortion. METHODS: A nested case-control study within the Danish National Birth Cohort, a cohort of 100,418 pregnancies recruited from 1996-2002. Women were recruited in first trimester of pregnancy and followed prospectively. Median gestational age at enrolment was 8 weeks (25 and 75 percentiles: 7 weeks; 10 weeks). During pregnancy, a blood sample was collected at gestational week 6-12 and stored in a bio bank. For this study, a case sample of 218 pregnancies was drawn randomly among the pregnancies in the cohort which ended with a miscarriage before 22 gestational weeks, and a reference group of 482 pregnancies was selected in a random fashion among all pregnancies in the cohort. From these pregnancies, serum samples were screened for antibodies against C. burnetii in a commercial enzyme-linked immunosorbent assay (ELISA). Samples that proved IgG or IgM antibody positive were subsequently confirmatory tested by an immunofluorescence (IFA) test. RESULTS: Among cases, 11 (5%) were C. burnetii positive in ELISA of which one was confirmed in the IFA assay compared to 29 (6%) ELISA positive and 3 IFA confirmed in the random sample. CONCLUSIONS: We found no evidence of a higher prevalence of C. burnetii antibodies in serum samples from women who later miscarried and the present study does not indicate a major association between Q fever infection and spontaneous abortion in humans. Very early first trimester abortions were, however, not included in the study.

[Q-fever caused spontaneous abortion]. / Q-feber som årsag til spontan abort.

Q-fever is a zoonotic infection. Pregnant women constitute a specific risk group as the infection may cause spontaneous abortion, intrauterine death, growth retardation, oligohydramnios and premature birth. A 39 year-old veterinarian had a spontaneous abortion in pregnancy week seven. During the first weeks of her pregnancy, she handled birth by-products from cows with Q-fever. The Q-fever titres revealed that she was most likely infected in very early pregnancy. According to the literature, infection in the first trimester constitutes a specific risk of spontaneous abortion.