SARS-CoV-2 Antibodies in Breastmilk Three and Six Months Postpartum in Relation to the Trimester of Maternal SARS-CoV-2 Infection-An Exploratory Study.

The immune system of neonates is immature and therefore knowledge of possible early-life protection against SARS-CoV-2 infection, such as breastfeeding, is of great importance. Few studies have investigated the presence and duration of SARS-CoV-2 antibodies in breastmilk in relation to the trimester of maternal infection during pregnancy, and none with successful participation from all three trimesters. This study has dual objectives (1) in relation to the trimester of infection to examine the frequency, concentration and duration of IgA and IgG antibodies in breastmilk and blood serum in the third and sixth month post-partum in former SARS-CoV-2-infected mothers and (2) to examine the association in pediatric emergency admission of children within the first six months of life compared to children of non-SARS-CoV-2-infected women. The first objective is based on a prospective cohort and the second is based on a nested case-control design. The study participants are women with a former SARS-CoV-2 infection during pregnancy, whose serology IgG tests at delivery were still positive. Maternal blood and breastmilk samples were collected at three and six months postpartum. Serum IgA frequency three months pp was 72.7% (50%, 90% and 60% in the first, second and third trimester) and 82% six months pp (67%, 91% and 82% in the first, second and third trimester). Breastmilk IgA frequency three months pp was 27% (16.6%, 36% and 20% in first, second and third trimester) and 28% six months pp (0%, 38% and 28% in the first, second and third trimester). The highest IgA concentration in breastmilk was found six months post-partum with infection in the third trimester. Serum IgA was detectable more than 400 days post infection, and serum IgG above threshold was found 430 days after date of infection. We found no correlation between serum IgA and breastmilk IgA, nor between serum IgG and breastmilk IgA regardless of the trimester of infection.

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.

Chorionicity and gestational diabetes mellitus in twin pregnancies in relation to placental weight.

BACKGROUND: Gestational diabetes mellitus (GDM) is glucose intolerance first detected during pregnancy. Twin pregnancies have a higher risk of GDM, likely due to increased placental mass and elevated placental lactogen levels. OBJECTIVE: The aims of this study were 1) to assess the impact of chorionicity on the development of GDM in twin pregnancies and 2) to assess a possible association between placenta weight and the development of GDM. METHODS: We conducted a prospective cohort study of all women with twin pregnancies (N = 819) at the department of Obstetrics and Gynecology, Lillebaelt University Hospital, Kolding, Denmark, between January 1, 2007 and April 30, 2019. Information on chronicity was determined at the first visit with ultrasonic imaging, during weeks' gestation 11-13. Oral glucose-tolerance test was performed to diagnose gestational diabetes mellitus. RESULTS: Among 819 twins, 17.8 % were monochorionic twins and 82.2 % were dichorionic twins. There were no statistically significant difference of GDM prevalence between monochorionic twins group 7.4 % and dichorionic twins group 9.8 % (P = 0.42). Placenta's weight in dichorionic twins was larger compared with monochorionic twins. No association was found between the weight of placenta and the prevalence of GDM (P = 0.21), even after adjustment for body mass index, gestational age, and fertility treatment (P = 0.87). CONCLUSIONS: Our study could not find an association between chorionicity, placental weight, and GDM. It is, therefore, possible that twin pregnancies, regardless of chorionicity and placental weight, have the same risk for GDM.

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.

Term Delivery Complicated by Uterine Rupture with No Prior History of Cesarean Section or Uterine Curettage Following Oxytocin Use and Arrest in Second Stage of Labor: A Case Report.

BACKGROUND Uterine rupture during delivery in an unscarred uterus may be associated with oxytocin dose during second stage arrest and with underlying maternal factors. This report is of a 34-year-old woman, gravida 5, para 3, with no previous history of cesarean section (CS), who had a uterine rupture at term delivery following the use of oxytocin for second-stage arrest. CASE REPORT A 34-year-old Afghani woman, gravida 5, para 3 was admitted at term for delivery. The current pregnancy had been normal and the estimated birth weight was approximately 4000 g. There was no history of steroid treatment or any underlying connective tissue disease, and no history of dilation and curettage. Oxytocin was given as per protocol, starting at 20 ml/h of a dilution of 10 IU/1 L natrium chloride (NaCl). Subsequent labor progress was complicated by arrest of descent in the second stage of labor, necessitating cesarean section delivery. After opening the abdominal wall, a uterine rupture with several large blood clots was discovered, freely floating in the peritoneal space, about 500 ml in volume. The rupture stretched from the left side of the uterine body and down into the thin lower segment. The tissue in this area had diffuse hematoma. CONCLUSIONS Although uterine rupture mostly occurs in women with previous CS, this report has shown that uterine rupture can occur in pregnancy complicated by arrest in the second stage of labor.

Neonatal and maternal outcomes with elective cesarean section compared to induction of labor in twin pregnancies: A prospective cohort study.

OBJECTIVES: The aim of this study was to compare neonatal and maternal outcomes in twin pregnancies with elective cesarean section (ECS) and induction of labor (IOL) to better inform women during the counselling process. MATERIALS AND METHODS: We conducted a cohort study including all twin pregnancies referred to the Department of Obstetrics at Kolding University Hospital, Denmark between January 2007 to April 2019 (n = 819). The primary analysis compared maternal and neonatal outcomes in pregnancies planned for IOL with those planned for ECS after week 34. A secondary analysis compared maternal and neonatal outcomes in pregnancies who underwent IOL followed by successful vaginal delivery with outcomes in those who underwent ECS. RESULTS: Among 587 eligible twin pregnancies, the rates of unplanned CS did not differ between those planned for ECS compared to those planned for IOL (38% vs. 33%; p = 0.27). IOL resulted in successful vaginal delivery in 67% (155/231) of those planned for IOL. Maternal outcomes did not differ between women who were planned for, or received, delivery with either IOL or ECS. Regarding neonatal outcomes, significantly more neonates required treatment with C-PAP in ECS group, than in the IOL group, and a higher median number of maturity days among mothers planned for ECS. However, no other significant difference in neonatal outcomes was observed when comparing successful IOL with successful ECS. CONCLUSION: Induction of labor was not associated with worse outcomes compared to elective caesarean section in this large cohort of routinely handled twin pregnancies. In women with twin pregnancies indicated for delivery, who does not go into spontaneous labor, induction of labor is a safe option for both the mothers and their neonates.

Bilateral tubal pregnancy in a woman without risk factors.

In this case report, a woman with no risk factors was admitted with bilateral tubal ectopic pregnancy. Bilateral ectopic pregnancy is a rare clinical condition with clinical findings which in their symptoms do not differ from those of unilateral ectopic pregnancy. The condition can therefore easily be missed. The risk of rupture and haemorrhagic shock might be increased because of the increased danger of both tubes presenting with complications. Thus, it is important to examine both adnexa by transvaginal ultrasound. Even if unilateral ectopic pregnancy is considered before operation, the inspection of the abdomen, especially of the other fallopian tube, must always be done during surgery.

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.

Polymerase chain reaction for Group B Streptococci (GBS) at labor highly correlates with vaginal GBS load.

OBJECTIVE: To explore factors associated with a high vaginal GBS load during labor considering (1) the recto-vaginal GBS load at 35-37 weeks' gestation determined by culture and (2) the vaginal GBS colonization determined by a polymerase chain reaction (PCR) assay during labor. METHODS: From an unselected cohort of 902 pregnant women, we obtained (1) recto-vaginal swabs for culture of GBS at 35-37 weeks' gestation (GBSrectovag-36), (2) vaginal swabs for GBS PCR detection at labor (PCRvag-labor), and (3) vaginal swabs for culture of GBS at labor (GBSvag-labor). The GBS load was classified semi quantitatively according to a culture protocol without prior broth enrichment of the swab samples: none (0), few (+), some (++), or many (+++) GBS colonies. RESULTS: Among 902 unselected pregnant women, 859 (95%) had a vaginal swab culture taken at labor, which was classified semi quantitatively. High load GBSvag-labor (+++) were found in 31 participants. GBSrectovag-36 showed a sensitivity of 90% (28/31) and a PPV of 23% (28/121), whereas PCRvag-labor had a sensitivity of 98% (30/31, non-significant difference) and a PPV of 42% (30/71, p < .01). PCR at labor had a lower sensitivity (78%) for detection of vaginal colonization with GBS at labor (any load) compared to recto/vaginal colonization with GBS at 36 weeks (92%). Vaginal colonization with GBS at 36 weeks seemed to have a lower sensitivity for detecting GBS in vagina at labor for high load (48%) and for any load (39%). CONCLUSION: PCR at labor has higher detection rate (non-significant) and PPV in identification of laboring women with a high load of vaginal GBS compared with recto-vaginal culture at 36 weeks' gestation.

Child-Mother Index: a new risk factor for selected adverse maternal birth outcomes.

BACKGROUND: Over decades, obstetricians have evaluated a range of risk factors to improve the prediction of adverse birth outcomes. OBJECTIVE: This study aimed to assess the effectiveness of the Child-Mother Index as a risk factor indicator for selected adverse maternal birth outcomes. STUDY DESIGN: We assessed the Child-Mother Index by multinomial regression models using register-based data containing all singleton births in Denmark in 2009 with a gestational age between 37+0 and 41+6 weeks. The Child-Mother Index is defined as the weight of the newborn divided by the squared maternal height. RESULTS: Data from 47,007 births were included. Both the Child-Mother Index mean and Child-Mother Index median were 12.6 hg/m2 (range, 4.8-22.4). In the multivariable model, the relative risk ratios for Child-Mother Index above 14.1 hg/m2 were 2.2 (95% confidence interval, 1.6-3.1) for third- and fourth-degree perineal tears, 2.0 (1.6-2.5) for nonelective cesarean delivery, and 1.0 (0.8-1.3) for instrumental procedures. Equivalent figures for a Child-Mother Index below 11.2 hg/m2 were 0.6 (0.4-1.0), 1.0 (0.8-1.2), and 0.7 (0.6-0.9), respectively.By comparing a multivariable model with the Child-Mother Index included with a model without the Child-Mother Index included using a likelihood ratio test, a statistically significant difference was found in favor of the Child-Mother Index inclusion (P<.001). CONCLUSION: The Child-Mother Index constitutes a potential useful risk factor indicator for statistical analyses on data after birth. The value of the Child-Mother Index based on the estimated fetal weight before birth deserves evaluation.

Urine dipstick for predicting intrapartum recto-vaginal colonisation by group B streptococci.

INTRODUCTION: In pregnant women, bacteriuria with group B streptococci (GBS) may be associated with a high degree of recto-vaginal GBS colonisation and therefore an increased risk of early-onset GBS disease. The aim of this study was to assess the performance of routine use of dipstick urine analysis during pregnancy for prediction of recto-vaginal GBS colonisation at the time of labour. METHODS: Among 902 unselected Danish pregnant women, we obtained results from 1) dipstick urine analysis, 2) urine culture carried out during pregnancy, if indicated, and 3) recto-vaginal culture at labour. The inclusion criteria were age > 18 years and gestational age ≥ 37 weeks. RESULTS: Intrapartum recto-vaginal GBS colonisation was predicted by a positive urine dipstick with 5% sensitivity only. CONCLUSION: Dipstick urine analysis had a low sensitivity for predicting intrapartum recto-vaginal colonisation with GBS. FUNDING: none. TRIAL REGISTRATION: not relevant.

Vitamin D and the risk of dystocia: A case-control study.

BACKGROUND: Dystocia is one of the most common causes of cesarean section in nulliparous women. Studies have described the presence of vitamin D receptors in the myometrium, but it is still unclear whether vitamin D affects the contractility of the smooth muscles. We therefore aimed to determine the association between the vitamin D serum level at labor and the risk of dystocia. METHOD: We conducted a case-control study between January 2012 and June 2017. Cases were primiparous women, with spontaneous onset of labor, who gave birth by cesarean section due to dystocia. Controls were primiparous women with a spontaneous vaginal delivery. We included 60 women (30 cases and 30 controls) in the analysis. The differences between cases and controls were assessed using chi-squared test for categorical variables and two-sample t-test or unequal t-test for continuous variables, as appropriate, after evaluation of whether they followed the normal distributions. RESULTS: The mean serum 25-hydroxyvitamin D concentrations were 53.1nmol/l (95%CI; 45.2 to 60.9) among cases and 69.9nmol/l (95%CI; 57.5 to 82.4) among controls (P = 0.02). The mean plasma parathyroid hormone levels were 2.25 pmol/l and 2.38, respectively (P = 0.57). Even though 78% of all women reported taking a minimum of 10µg/day of vitamin D throughout pregnancy, 43% had vitamin D insufficiency, defined as serum 25-hydroxyvitamin D levels below 50nmol/l. CONCLUSIONS: In a Danish group of women having a cesarean section due to dystocia, we found decreased vitamin D levels.

Risk-based screening and intrapartum group B streptococcus polymerase chain reactionresults reduce use of antibiotics during labour.

INTRODUCTION: This study investigated the feasibility of a risk-based screening approach combined with testing of Group B streptococcus (GBS) by polymerase chain reaction (PCR), the effect on use of intrapartum antibiotic prophylaxis (IAP) and the impact on the incidence of early-onset GBS infection (EOGBS). METHODS: During one year, 551 women giving birth at Lillebaelt Hospital, Denmark, having one or more risk factors for EOGBS (previous birth of infant with EOGBS, GBS bacteriuria during current pregnancy, gestational age less than 37 weeks, rupture of membranes greater than 18 hours, and temperature ≥ 38 °C) were tested by a GBS PCR assay intrapartum. IAP was administered when the woman tested positive. RESULTS: Among 2,889 women in labour, 19.1% (n = 551) had one or more risk factors for EOGBS, and 5.1% (n = 146) had both risk factors for EOGBS and a positive intrapartum GBS PCR test. In total, 185 women with risk factors for EOGBS received IAP. If the former risk-based approach had been applied, 551 women giving birth would have received IAP. Implementing IAP based on the GBS PCR results produced a two-thirds reduction of IAP. No children were diagnosed with EOGBS. CONCLUSIONS: The GBS PCR assay was easy to perform and provided test results within 50 minutes. Implementation of risk-based screening combined with intrapartum GBS PCR testing reduces the use of IAP by two thirds compared with risk-based screening alone, thus minimising antibiotic resistance. The study material was too small to evaluate the effect on the incidence of EOGBS. Since EOGBS is a rare disease, more studies are required. FUNDING: The study was supported by Forskningsraadet Lillebaelt Hospital, Udviklingsraadet Lillebaelt Hospital, Johs. M. Klein og Hustrus Mindelegat, the Region of Southern Denmark, Farusa Emballage A/S. TRIAL REGISTRATION: not relevant.

Number of colony forming units in urine at 35-37 weeks' gestation as predictor of the vaginal load of Group B Streptococci at birth.

OBJECTIVE: To evaluate GBS colony numbers in the urine at 35-37 weeks' gestation to predict the load of GBS-colonization of the vagina at birth. STUDY DESIGN: In this prospective observational study, we included 902 unselected pregnant women. Exposure was GBS colony forming units (CFU) per mL urine at 35-37 weeks' gestation. Outcome was vaginal GBS colonization at birth as assessed by a semi-quantitative culture of a vaginal swab sample (negative, +1, +2, +3). RESULTS: Bacteriuria with GBS at 35-37 weeks' gestation performed with a sensitivity of 30% concerning any degree of vaginal GBS colonization at birth (31 of 104 cases); 19% for light (+1), 17% for medium (+2), and 52% for high load (+3) vaginal GBS colonization. The colony count in case of GBS bacteriuria at 35-37 weeks' gestation performed with positive predictive values of 35% for <104 CFU/mL, 70% for 104 CFU/mL, and 67% for >104 CFU/mL. CONCLUSION: Even though the urinary GBS CFU at 35-37 weeks' gestation is strongly associated with a high load of vaginal GBS colonization intrapartum, it may not perform satisfactorily as a standalone-screening marker for risk of early-onset GBS disease.

Intrapartum PCR assay versus antepartum culture for assessment of vaginal carriage of group B streptococci in a Danish cohort at birth.

The aim of this study was to compare the performances of two strategies for predicting intrapartum vaginal carriage of group B streptococci (GBS). One strategy was based on an antepartum culture and the other on an intrapartum polymerase chain reaction (PCR). We conducted a prospective observational study enrolling 902 pregnant women offered GBS screening before delivery by two strategies. The Culture-strategy was based on vaginal and rectal cultures at 35-37 weeks' gestation, whereas the PCR-strategy was based on PCR assay on intrapartum vaginal swab samples. An intrapartum vaginal culture for GBS was used as the reference standard from which the performances of the 2 strategies were evaluated. The reference standard showed a GBS-prevalence of 12%. The culture-strategy performed with a sensitivity of 82%, specificity of 91%, positive predictive value (PPV) of 55%, negative predictive value (NPV) of 98%, and Likelihood ratio (LH+) of 9.2. The PCR-strategy showed corresponding values as sensitivity of 83%, specificity of 97%, PPV of 78%, NPV of 98%, and LH+ of 27.5. We conclude that in a Danish population with a low rate of early-onset neonatal infection with GBS, the intrapartum PCR assay performs better than the antepartum culture for identification of GBS vaginal carriers during labor.

Low hepatitis B prevalence among pre-school children in Denmark: saliva anti-HBc screening in day care centres.

Although Denmark has a low hepatitis B virus (HBV) prevalence, HBV transmission has been reported in Danish day-care centres. The aim of this study was to validate saliva anti-HBc testing as a method for HBV screening, the applicability of saliva sampling to pre-school children, and to determine the HBV prevalence in Danish day-care centres with a high proportion of immigrants. For validation, paired saliva and plasma samples were obtained from blood donors and injecting drug users. Employees and children in day-care centres with a high proportion of immigrant children were offered saliva screening followed by blood test if positive. The specificity and sensitivity of anti-HBc tests on saliva was 100% (102 blood donors and four injecting drug users) and 85.9% (61 of 71 anti-HBc-positive injecting drug users), respectively. In all samples from HBsAg (n = 7) or anti-HBc IgM-positives (n = 9), anti-HBc was detected in saliva. Adequate saliva samples were obtained from 93% (588/634) of children and 100% (166/166) of employees participating in the day-care centre survey. Among children 55% were of non-Scandinavian origin and only one (0.2%, 95% CI [0.0; 1.0]) was HBV positive. Among employees the corresponding values were 22% and 7 (4.2%). The positive predictive value of the saliva test was 25% (1/4) among children and 88% (7/8) among adults. In conclusion, saliva testing is feasible for HBV screening among children in low prevalence populations, but any anti-HBc reactivity should be confirmed by plasma analysis. The HBV prevalence in pre-school children in Denmark is low even among immigrants from endemic areas.