Spontaneous Hemoperitoneum in Pregnancy and Endometriosis: A New Challenge in a Known Disease.

Importance: Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare life-threatening event previously associated with endometriosis. Although pregnancy is thought to improve the symptoms of endometriosis, abrupt intraperitoneal bleeding can occur, jeopardizing both maternal and fetal outcomes. Objective: The aim of this study was to review the published information regarding SHiP pathophysiology, presentation, diagnosis, and management in a flowchart approach. Evidence Acquisition: A descriptive review of published articles in the English-language was carried out. Results: SHiP most commonly presents in the second half of pregnancy with a combination of abdominal pain, hypovolemia, a decline in hemoglobin level, and fetal distress. Nonspecific gastrointestinal symptoms are not uncommon. Surgical management is suitable in most scenarios and avoids complications such as recurrent bleeding and infected hematoma. Maternal outcome has improved greatly, whereas perinatal mortality remained unchanged. In addition to physical strain, SHiP was reported to have a psychosocial sequela. Conclusions and Relevance: A high index of suspicion is required when patients present with acute abdominal pain and signs of hypovolemia. Early use of sonography contributes to narrowing down the diagnosis. Health care providers should be familiar with the SHiP diagnosis because early identification is crucial when attempting to safeguard maternal and fetal outcomes. Maternal and fetal requirements are often contradictory, creating a greater challenge in decision-making and treatment. A multidisciplinary team approach should coordinate the treatment, whenever a SHiP diagnosis is suspected.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013-2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and "Dana Dwek" Children's Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4-6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes-allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Midgestational pre-labor spontaneous uterine rupture: a systematic review.

OBJECTIVE: Second and early third-trimester uterine rupture in a non-laboring woman is a very rare and life-threatening condition for both mothers and newborns. However, there are scant epidemiologic data on this event. STUDY DESIGN: Literature searches using Medical Subject Headings (MeSH) and non-MeSH terms were conducted in the PubMed/MEDLINE, Google Scholar and Embase databases from 1988 to 2020. Abstracts were reviewed and selected if they reported on uterine rupture in the second and third trimester. Uterine rupture was characterized as a full-thickness uterine wall defect. A total of 80 singleton intrauterine pregnancies between gestational ages of 14 and 34 weeks' gestation were included. RESULTS: The mean gestational age at diagnosis of uterine rupture was 22.4 ± 5.4 weeks. The associated events in obstetric history for uterine rupture were: ≥1 previous cesarean section (45%; 36/80 of the cases), previous uterine rupture (10%; 8/80), previous classical uterine incision (7.5%; 6/80), myomectomy (25%; 20/80) and congenital uterine malformations (16.3%; 13/80 of the cases). Uterine ruptures were associated with a short IP interval in 13.7% (11/80) and 43.7% (35/80) were associated with abnormal placentation: placenta accreta spectrum (PAS) disorders (n = 26), placenta previa (n = 2) and placenta previa and PAS (n = 7). The rate of related prenatal ultrasound findings was 67.5%. Cesarean hysterectomy was performed in 27% of the cases. Maternal death was reported in 2.5% (2/80). For the neonates delivered ≥24 weeks' gestation (n = 27) peripartum fetal death was reported in 33.3% (9/27). CONCLUSIONS: Midgestational pre-labor spontaneous uterine rupture is not an anecdotal event and may follow the worldwide increasing rate of cesarean sections. Health care providers should be familiar with the associated factors, presenting symptoms and complications of this obstetric emergency.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring. Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns. Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders. Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83-68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70-8.23) µIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27-13.53) µg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36-12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6-24.9) µg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19-24.9). Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Metabolic biomarkers of small and large for gestational age newborns.

BACKGROUND: Small for gestational age (SGA) and large for gestational age (LGA) newborns are at increased risk for developmental, metabolic and cardiovascular morbidities. AIMS: To compare the metabolic biomarkers of SGA and LGA infants with those of appropriate for gestational age (AGA) newborns in order to shed more light on a possible pathogenesis of those morbidities. STUDY DESIGN: An observational retrospective study. SUBJECTS: 70,809 term newborns divided into AGA, SGA, LGA, and severe subcategories (<3rd percentile or ≥97th percentile). OUTCOME MEASURES: 18 metabolites were measured by dried blood tandem mass spectrometry and compared in between groups in univariate and multivariate logistic regression. RESULTS: SGA newborns had a significant likelihood for elevated methionine, proline, free carnitine, and reduced valine levels compared to AGA newborns (P < .0001). Severe SGA showed more apparent trends including elevated leucine. LGA newborns had a significant likelihood for low citrulline, glutamine, proline, tyrosine, and elevated leucine levels (P ≤ .0033). Severe LGA newborns showed the same trends, with the exception of citrulline and glutamine. CONCLUSIONS: SGA and LGA newborns demonstrate distinct metabolic biomarkers in newborn screening. Most of the altered metabolites in the SGA group were elevated while those in the LGA group were decreased in comparison to AGA newborns. These trends were more apparent in the severe SGA subgroup while they mostly remained the same in the severe LGA subgroup. Whether these metabolic changes are involved with or can predict long-term outcome awaits further trials.

Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women-The Role of Sex Hormones.

Pertussis containing vaccine is recommended for pregnant women to protect neonates prior to being fully immunized against the disease. The immune response during pregnancy may be impacted by changes in the hormonal status. The aim of this study was to evaluate the immune response to pertussis immunization in pregnancy and to assess the role of sex hormones. In a cross-sectional study, blood samples were drawn from 174 pregnant and 74 non-pregnant women 45-60 days following immunization. Anti-pertussis toxin (Anti-PT) IgG antibody levels, estrogen, and progestogen concentrations were compared between the two groups. Multiple logistic regression analysis was used to examine the association between serum antibody and sex hormone concentrations in each group, controlling for age, body mass index (BMI), and smoking status. The geometric mean concentration (GMC) of anti-PT IgG antibody was significantly higher in non-pregnant women compared with pregnant women (median of 2.09 and 1.86, interquartile range = 2.36-1.8 and 2.11-1.16 respectively, p < 0.0001). Among pregnant women, the anti-PT IgG antibody GMC was negatively associated with both progesterone (odds ratio = 0.300, 95% CI = 0.116, 0.772, p = 0.013) and estrogen (odds ratio = 0.071, 95% CI = 0.017, 0.292, p < 0.0001), after controlling for age, BMI, and smoking. Pregnancy was associated with lower anti-PT IgG antibody levels (odds ratio = 0.413, 95% CI = -0.190, 0.899, p = 0.026). This appears to be at least partially explained by the higher levels of hormones during pregnancy. These findings demonstrate the important role of sex hormones in the response to pertussis vaccine during pregnancy and can help to evaluate the optimum vaccination schedule.

Impact of the COVID-19 Pandemic on Excess Perinatal Mortality and Morbidity in Israel.

OBJECTIVE: The 2020 COVID-19 pandemic has been associated with excess mortality and morbidity in adults and teenagers over 14 years of age, but there is still limited evidence on the direct and indirect impact of the pandemic on pregnancy. We aimed to evaluate the effect of the first wave of the COVID-19 pandemic on obstetrical emergency attendance in a low-risk population and the corresponding perinatal outcomes. STUDY DESIGN: This is a single center retrospective cohort study of all singleton births between February 21 and April 30. Prenatal emergency labor ward admission numbers and obstetric outcomes during the peak of the first COVID-19 pandemic of 2020 in Israel were compared with the combined corresponding periods for the years 2017 to 2019. RESULTS: During the 2020 COVID-19 pandemic, the mean number of prenatal emergency labor ward admissions was lower, both by daily count and per woman, in comparison to the combined matching periods in 2017, 2018, and 2019 (48.6 ± 12.2 vs. 57.8 ± 14.4, p < 0.0001 and 1.74 ± 1.1 vs. 1.92 ± 1.2, p < 0.0001, respectively). A significantly (p = 0.0370) higher rate of stillbirth was noted in the study group (0.4%) compared with the control group (0.1%). All study group patients were negative for COVID-19. Gestational age at delivery, rates of premature delivery at <28, 34, and 37 weeks, pregnancy complications, postdate delivery at >40 and 41 weeks, mode of delivery, and numbers of emergency cesarean deliveries were similar in both groups. There was no difference in the intrapartum fetal death rate between the groups. CONCLUSION: The COVID-19 pandemic stay-at-home policy combined with patient fear of contracting the disease in hospital could explain the associated higher rate of stillbirth. This collateral perinatal damage follows a decreased in prenatal emergency labor ward admissions during the first wave of COVID-19 in Israel. KEY POINTS: · Less obstetrical ER attendance is observed during the pandemic.. · There is a parallel increase in stillbirth rate.. · Stillbirth cases tested negative for COVID-19.. · Lockdown and pandemic panic are possible causes..

Second-trimester and early third-trimester spontaneous uterine rupture: A 32-year single-center survey.

BACKGROUND: Second-trimester and early third-trimester uterine rupture in a nonlaboring woman is a very rare and life-threatening condition for both mothers and newborns. We aimed to present clinical characteristics, prenatal findings, and maternal and neonatal outcomes following second-trimester and early third-trimester spontaneous antepartum uterine rupture in our institute. METHOD: The medical records of all women with full-thickness second-trimester and early third-trimester uterine rupture treated in our department from 1988 to 2019 were retrieved from the institutional database and reviewed. Small uterine defects, incomplete ruptures, and silent uterine incision dehiscence were excluded. RESULTS: From 1988 to 2019, 213 665 deliveries were recorded in our institute. Of these, 12 patients experienced second-trimester or early third-trimester spontaneous uterine rupture. Obstetric history revealed that 50% of the women in each period had undergone previous classical uterine incisions and 50% had a short interpregnancy (IP) interval. The mean age at diagnosis of uterine rupture was 26.3 ± 5.1 weeks. The ruptures were associated with abnormal placentation in 10 cases (83.3%): placenta previa (n = 7); and placenta previa and percreta (n = 3). No maternal mortality occurred. Seven of the 10 (70%) viable newborns survived. CONCLUSIONS: The increasing rates of cesarean births (CB) may lead to iatrogenic complications including midgestational prelabor spontaneous uterine rupture, an obstetric emergency, which is hard to diagnose. Maternal and neonatal outcomes can be optimized by a greater awareness of the risk factors, recognition of clinical signs and symptoms, and the availability of ultrasound to assist in establishing a diagnosis to enable prompt surgical intervention.

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance.

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus. This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns. Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables. Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns. This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Is scanning for vasa previa important for singleton pregnancies that started as multiple conceptions?

OBJECTIVES: Vasa previa (VP) is a congenital placentation disorder in which fetal vessels run across the internal os of the cervix under the fetal presentation. This rare condition is associated with a high rate of perinatal morbidity and mortality when undetected before delivery. Roughly 85% of all cases of VP can be associated with one or more identifiable risk factors including in-vitro fertilization (IVF), multiple gestations, bilobed, succenturiate or low-lying placentas, and velamentous cord insertion (VCI). Recent evidence indicates the need for standardized prenatal targeted scanning protocols of pregnancies at risk of VP. The present study reports on pregnancies that began with multiple gestations but ended with a single fetus diagnosed with VP. STUDY DESIGN: We retrospectively collected and reviewed medical records from 2006 to 2018 of early multiple pregnancies that ended with a single fetus diagnosed with VP in our medical center, including three cases of twin gestation complicated by a vanishing twin and a case of multifetal reduction in triplet pregnancy. This retrospective cohort study was approved by our Institutional Clinical Research Committee. RESULTS: The database search identified 50 pregnancies that started as multiple gestations but continued as singletons. Of these, 4 pregnancies were diagnosed with VP, for a prevalence of 8.0%. For two of the four cases, the diagnosis was made during delivery as expressed by a low Apgar score at 1 and 5 min, a low cord blood pH value, newborn resuscitation, blood product transfusion, and NICU supervision. There was a statistically significant difference in the prevalence of VP in pregnancies that started as multiple gestations but continued later as singletons compared to multiple pregnancies (8.0% vs. 0.2% respectively, p < 0.0001). The OR for VP in pregnancies that started as multiple gestations but continued as singletons was 41.1 (95% CI, 12.77-131.94). CONCLUSIONS: Our findings suggest there is an increased risk of VP in conceptions that started as viable multiple gestations but continued later as singletons. If our findings supported by others, it may be prudent to consider all twins at the beginning of pregnancy to be at risk for VP, irrespective of the actual number of life fetuses at later stages of gestation.

Postpartum retained products of conception: Retrospective analysis of the association with third stage of labor placental complications.

OBJECTIVE: To compare the prevalence of postpartum retained products of conception (RPOC) among parturients with a history of third stage of labor placental complications and parturients without those complications. STUDY DESIGN: All women operated for postpartum RPOC following vaginal delivery by hysteroscopy or suction curettage between January 2013 and December 2017 were included in the study. Their medical records were reviewed for the occurrence of third stage of labor placental complications (including early postpartum hemorrhage treated with uterotonics, manual separation of the placenta, and revision of the uterine cavity for removal of cotyledons). RESULTS: The study cohort included 172 women operated for postpartum RPOC following vaginal delivery by operative hysteroscopy (143 cases, 83.1%) or by suction curettage (29 cases, 16.9%). Third stage of labor placental complications were reported in 65 (37.8%) cases, while 107 (62.2%) women had an uncomplicated third stage of labor. When considering all vaginal deliveries in our institution during the study period, the risk for RPOC was significantly higher among parturients with third stage of labor placental complications compared to those with an uneventful third stage of labor (3.7% versus 0.3%, p < 0.001, Odds ratio = 12.5, 95% confidence interval 9.0-17.3). CONCLUSION: Postpartum RPOC following vaginal delivery were more common in parturients with third stage of labor placental complications. However, the majority of postpartum RPOC cases were diagnosed in women reported to have an uncomplicated third stage of labor. Thus, focused postpartum ultrasound follow-up of women considered at risk for RPOC will not identify all cases.

Impact of targeted scanning protocols on perinatal outcomes in pregnancies at risk of placenta accreta spectrum or vasa previa.

BACKGROUND: Placenta accreta spectrum and vasa previa (VP) are congenital disorders of placentation associated with high morbidity and mortality for both mothers and newborns when undiagnosed before delivery. Prenatal diagnosis of these conditions is essential to allow multidisciplinary management and thus improve perinatal outcomes. OBJECTIVE: The objective of the study was to compare perinatal outcome in women with placenta accreta spectrum or vasa previa before and after implementation of targeted scanning protocols. STUDY DESIGN: This retrospective study included 2 nonconcurrent cohorts for each condition before and after implementation of the corresponding protocols (2004-1012 vs 2013-2016 for placenta accreta spectrum and 1988-2007 vs 2008-2016 for vasa previa). Clinical reports of women diagnosed with placenta accreta spectrum and vasa previa during the study periods were reviewed and outcomes were compared. RESULTS: In total, there were 97 cases of placenta accreta spectrum and 51 cases with vasa previa, all confirmed at delivery. In both cohorts, the prenatal detection rate increased after implementation of the scanning protocols (28 of 65 cases [43.1%] vs 31 of 32 cases [96.9%], P < .001, for placenta accreta spectrum and 9 of 18 cases [50%] vs 29 of 33 cases [87.9%], 87.9%, P < .01 for vasa previa). The perinatal outcome improved also significantly in both cohorts after implementation of the protocols. In the placenta accreta spectrum cohort, the estimated blood loss and the postoperative hospitalization stay decreased between periods (1520 ± 845 vs 1168 ± 707 mL, P < .01, and 10.9 ± 14.1 vs 5.7 ± 2.2 days, P < .05, respectively). In the vasa previa cohort, the number of 5 minute Apgar score ≤5 and umbilical cord pH <7 decreased between periods (5 of 18 cases [27.8%] vs 1 of 33 cases [3%]; P < .05, and 4 of 18 cases [22.2%] vs 1 of 33 cases [3%], P < .05, respectively). CONCLUSION: The implementation of standardized prenatal targeted scanning protocols for pregnant women with risk factors for placenta accreta spectrum and vasa previa was associated with improved maternal and neonatal outcomes. The continuous increases in the rates of caesarean deliveries and use of assisted reproductive technology highlights the need to develop training programs and introduce targeted scanning protocols at the national and international levels.

Postpartum Retained Products of Conception: A Novel Approach to Follow-Up and Early Diagnosis.

PURPOSE: To investigate whether ultrasound follow-up for the detection of postpartum retained products of conception (RPOC) in women considered at risk for this condition may allow for early diagnosis. METHODS: Parturients at risk for RPOC underwent an ultrasound exam on the second postpartum day. Based on the ultrasound findings, women were either: (1) discharged to routine postpartum care in cases of normal scans, (2) invited for follow-up in cases of abnormal scans. We retrospectively analyzed the rates of women requiring uterine evacuation due to persistent abnormal scans. RESULTS: 761 parturients (out of 17 010 deliveries, 4.5 %) were included. Of those, 490 (64.4 %) women had a normal initial scan, but two of them were later readmitted for uterine evacuation. The remaining 271 (35.6 %) women were found to have an abnormal scan: (a) thickened endometrium > 10 mm with hypo- and hyper-echoes and negative Doppler flow considered low suspicion for RPOC was described in 260 cases, of whom 23 (8.8 %) underwent uterine evacuation with placental remnants confirmed in 12/23 (52.2 %), and (b) an echogenic mass with positive Doppler flow considered high suspicion for RPOC was described in 11 cases, all of whom underwent uterine evacuation, with placental remnants confirmed in 9/11 (81.8 %). The number of scans required to detect RPOC in one patient was 33. CONCLUSION: Postpartum ultrasound evaluation may allow for early diagnosis of RPOC in women considered at risk for this condition.