Unfolding of maternal-infant bonding amidst the COVID-19 pandemic: Social support as a risk and protective factor.

BACKGROUND: Social, familial, and physiological stressors may put maternal-infant bonding at risk. Therefore, it is plausible that the stressful conditions brought on by COVID-19 could influence maternal-infant bonding. This study aimed to elucidate the contribution of COVID-19-related experience to variance in maternal-infant bonding, beyond that of established risk factors and as moderated by social support. METHODS: This longitudinal, multicenter study examined the relationship of demographic and obstetric variables, social support, postpartum depression, as well as COVID-19-related fear, exposure, and subjective difficulty with mother-infant bonding six months following birth. Participants (N = 246) were women who delivered during the pandemics' strict lockdown period and were recruited 10 weeks after a liveborn delivery and followed up six months later. RESULTS: Relationship between fear of COVID-19 and maternal-infant bonding was moderated by social support: Amongst mothers with high levels of social support, fear of COVID-19 negatively predicted bonding. DISCUSSION: Results indicate that social support, while overall a protective factor for mother-infant bonding, may lose its buffering effect when fear of COVID-19 is high. This relationship was maintained even when early bonding experiences such as forced separation and the risk incurred by postpartum depression were accounted for. Implications for providers are discussed.

Maternal fear of COVID-19 and prevalence of postnatal depression symptoms, risk and protective factors.

This is a multicenter prospective observational study, aimed to evaluate the relations between Fear of COVID-19 and postpartum depression (PPD) symptom, that included a cohort of women who delivered during COVID-19 lockdown between 03 and 05/2020. Participants were approached after delivery and asked to complete an online questionnaire. Data was verified with each center's perinatal database. The validated Fear of COVID-19 Scale was in use. PPD was evaluated using the EPDS questionnaire as a categorical (≥13) and as a continuous scale. Pre-existing maternal disability was defined as any prior physiological/psychological chronic health condition. Continuous medical supervision or stress contributing complications at birth included pregnancy and labor related complications. Regression analysis and ROC statistics were utilized to evaluate associations and control for confounders. Overall, 421 women completed the questionnaires. Of them, 53(12.6%) had a high EPDS score. Fear of COVID-19 was positively correlated with PPD symptoms (r = 0.35,p = 0.000), ROC-AUC 0.73, 95% CI 0.65-0.81, p = 0.000. Following adjustment to confounders (maternal age, nulliparity, ethnicity, marital status, financial difficulties, maternal disability, accessibility to medical services, and continuous medical supervision (, the most important factor that correlated with depression symptoms was maternal disability (aOR 4.61,95% CI 1.96-10.82) followed by Fear of COVID-19 (aOR 1.11,95% CI 1.05-1.17). High accessibility to medical services during pregnancy (aOR 0.62, 95%CI 0.45-0.84) was protective for PPD symptoms. To conclude, during the COVID-19 pandemic, maternal disability and Fear of COVID-19 are positively associated with a high EPDS score. High medical accessibility during pregnancy was found as a protective factor for PPD.

The effect of placenta previa on fetal growth and pregnancy outcome, in correlation with placental pathology.

OBJECTIVE: To compare the clinical characteristics and placental histopathology between pregnancies complicated by placenta previa and controls. STUDY DESIGN: Between 2009 and 2015, cesarean deliveries (CDs) of 119 pregnancies with placenta previa were identified from which maternal outcomes, neonatal outcomes and placental pathology were reviewed. Results were compared with CDs matched for maternal age and pregnancy complications (control group, n=119). Placental lesions were classified into maternal and fetal vascular supply lesions and inflammatory response. Composite neonatal outcome was defined as one or more of early neonatal complications. Small-for-gestational age (SGA) was defined as birth weight ⩽10th percentile. RESULTS: Placentas from the previa group had higher rates of weights <10th percentile (P<0.001) and of maternal and fetal vascular supply lesions (P<0.001, for both). Higher rate of SGA (P=0.003) and worse composite neonatal outcome (P<0.001) were also observed in the previa group as compared with controls. After controlling for potential confounding bias using multivariable logistic regression models, placenta previa remained statistically significantly associated with placental maternal (adjusted odds ratio (aOR) 2.48, 95% confidence interval (CI) 1.2-4.9, P=0.009) and fetal (aOR 7.05, 95% CI 2.4-20.2, P<0.001) vascular supply lesions, SGA (aOR 10, 95% CI 2.3-44.2, P=0.002) and adverse neonatal outcome (aOR 6.87, 95% CI 2.9-11.8, P<0.001). CONCLUSIONS: More placental vascular supply lesions, higher rate of SGA and worse neonatal outcome characterized pregnancies with placenta previa in the current study. These findings may suggest that abnormal placentation is accompanied by suboptimal implantation that interferes with fetal growth.

The association between umbilical cord abnormalities and the development of non-reassuring fetal heart rate leading to emergent cesarean deliveries.

OBJECTIVE: To study the contribution of umbilical cord (UC) abnormalities in emergent cesarean deliveries (ECDs) for non-reassuring fetal heart rate (NRFHR) and to explore their association with placental histopathology and neonatal outcome. STUDY DESIGN: Data from 530 ECDs for NRFHR were reviewed for the occurrence of UC abnormalities. Those included the presence of UC entanglements, the number and location of loops, true knots and short cord (<50 cm). Multiple UC entanglements were defined as ⩾ 2 UC loops. Results were compared with 530 vaginal deliveries (VD group) matched for maternal age, parity and gestational age. Additionally, we compared neonatal outcome and placental histopathology in cases of ECDs with a single vs multiple UC entanglements. Neonatal outcome consisted of low Apgar score (⩽ 7 at 5 min), cord blood pH ⩽ 7.1 and composite neonatal outcome that was defined as one or more of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy or death. Placental lesions were classified as: lesions related to maternal vascular supply, lesions related to fetal vascular supply (consistent with fetal thrombo-occlusive disease), and maternal and fetal inflammatory responses. RESULTS: UC entanglements, true knots and short cords were all more common in the ECD group compared with the VD group, P<0.001, P=0.002, P=0.004, respectively. The rate of one loop entanglement did not differ between the groups. The rate of multiple UC entanglements was higher in the ECD group compared with the VD group, 20.6% vs 6.4%, respectively, P<0.001. ECDs with multiple compared with single UC entanglement had higher rate of adverse neonatal outcome, P=0.031, and more placental fetal vascular lesions 19.3% vs 8.1%, P=0.027, respectively. CONCLUSION: Multiple UC entanglements, true knots and short cords were more common in ECDs for NRFHR, suggesting their role in the development of fetal placental vascular lesions and adverse neonatal outcome.

The placental factor in early- and late-onset normotensive fetal growth restriction.

OBJECTIVE: Our objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA). STUDY DESIGN: Placentas from normotensive women who gave birth at 24-42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤ 34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates. RESULTS: The early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153). CONCLUSION: Early- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR.

Association of non-reassuring fetal heart rate and fetal acidosis with placental histopathology.

OBJECTIVE: To investigate the association between different placental lesions and non-reassuring fetal heart rate (NRFHR) pattern and fetal acidosis in labor. STUDY DESIGN: Placentas from 213 women who underwent cesarean section because of NRFHR with or without fetal acidosis (pH < 7.2) were classified by histopathologic findings: consistent with maternal circulation abnormalities i.e., namely, marginal or retroplacental hemorrhage (M0), maternal underperfusion, vascular (M1) or villous changes (M2), and those consistent with fetal thrombo-occlusive disease due to vascular (F1) or villous (F2) changes. Lesions were also analyzed by maternal (MIR) or fetal (FIR) origin of inflammatory responses. RESULTS: Cord blood pH was normal in 169 neonates (7.29 ± 0.04; control group) and <7.2 in 44 (7.10 ± 0.07; study group). The study group had higher rates of histologic chorioamnionitis; MIR was detected in 34.1% compared to17.8% of controls (p = 0.018), and FIR, in 18.2% compared to 6.5% (p = 0.016). Neonates in the study group had lower Apgar scores and longer hospitalization. CONCLUSIONS: Placental MIR and FIR are associated with cord blood acidosis in neonates delivered by cesarean section for NRFHR tracings in labor.

Pelvic arterial pseudoaneurysm-a rare complication of Cesarean section: diagnosis and novel treatment.

An uncommon cause of delayed postpartum hemorrhage is a pseudoaneurysm of the uterine artery. Pelvic arterial pseudoaneurysm is generally treated by laparotomy and hemostatic sutures or by uterine artery embolization. We describe two cases of late postpartum hemorrhage following Cesarean section, attributed to pelvic arterial pseudoaneurysm, that were successfully treated by direct thrombin injection under ultrasound guidance. Percutaneous or transvaginal ultrasound-guided direct thrombin injection is a simple procedure that does not require any sophisticated surgical or radiological equipment.

Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma.

OBJECTIVE: To determine the prognostic value of sonographically detected fetal hyperechogenic kidneys with normal amniotic fluid volume. METHODS: Seven cases of hyperechogenic fetal kidneys were identified by sonography over a 7-year period (1996--2002). Increased renal echogenicity was diagnosed when the renal parenchyma was of greater echogenicity than adjacent liver tissue. Amniotic fluid volume was measured by the semiquantitative sonographic technique known as the amniotic fluid index (AFI). RESULTS: Three of the live-born infants had autosomal dominant polycystic kidney disease and one had autosomal recessive polycystic kidney. In the remainder, autopsy study revealed multifocal renal dysplasia in two cases and normal kidneys in one. CONCLUSIONS: Increased renal echogenicity with normal amniotic fluid volume in a fetus without other anomalies is a difficult diagnostic dilemma. Although it is usually indicative of renal parenchymal disease with possible renal failure after birth or in early childhood, in some cases, it represents a normal variant. .

Expression and modification of PKA and AKAPs during meiosis in rat oocytes.

Meiosis in oocytes is initiated during fetal life, arrested around birth and resumed after puberty. Meiotic arrest is controlled by a cAMP-dependent protein kinase (PKA)-mediated cAMP action. We examined oocytes for the presence and modulation of the regulatory (R) subunits of PKA and the A-kinase anchoring proteins (AKAPs) that target PKA to specific subcellular locations. We found that rat oocytes express the two regulatory subunit isoforms, RI and RII of PKA. Immunocytochemistry revealed that the regulatory subunits underwent cellular translocation upon resumption of meiosis. We also demonstrated the presence of a novel 140 kDa AKAP, AKAP140 that exhibited a retarded electrophoretic motility at reinitiation of meiosis. The mobility shift of AKAP140 was susceptible to alkaline phosphatase and prevented by inhibition of p34cdc2 kinase. We conclude that rat oocytes express AKAP140 that is phosphorylated during meiosis. AKAP140 phosphorylation is sensitive to p34cdc2 kinase inhibitors. We hypothesize that AKAP140 and its phosphorylation state may influence the translocation of the R subunits of PKA throughout resumption of meiosis.

Inactivation of M-phase promoting factor at exit from first embryonic mitosis in the rat is independent of cyclin B1 degradation.

Exit from M-phase and completion of cell division requires inactivation of M-phase promoting factor (MPF), a heterodimer composed of the regulatory cyclin B1 and the catalytic p34cdc2 kinase. Inactivation of MPF is associated with cyclin B1 degradation that is brought about by the ubiquitin-proteasome pathway. Our study examined the role of the proteasome in the first mitosis of rat embryos and its participation in the regulation of cyclin B1 degradation and MPF inactivation. We show that in the early zygote the proteasome is evenly distributed in the ooplasm and the nucleus, whereas during mitosis it accumulates on the spindle apparatus. We further demonstrate that inhibition of proteasomal catalytic activity prevents 1-cell embryos from undergoing mitosis. This mitotic arrest is associated with the presence of relatively high amounts of cyclin B1, which unexpectedly does not result in elevated MPF activity. Our findings strongly imply that completion of the first embryonic division depends on proteasomal degradation and that cyclin B1 is included among its target proteins. They also provide the first evidence that MPF inactivation at this stage of development is not solely dependent upon cyclin B1 degradation and is insufficient to allow the formation of the 2-cell embryo.

Follicle-stimulating hormone treatment for men with idiopathic oligoteratoasthenozoospermia before in vitro fertilization: the impact on sperm microstructure and fertilization potential.

OBJECTIVE: To assess the effect of FSH on sperm fertilization potential and sperm intracellular structure in men with oligoteratoasthenozoospermia and a proven low fertilization rate in IVF. DESIGN: Prospective, randomized, partial crossover study. SETTING: IVF Unit, Golda Campus, Rabin Medical Center, Petah Tikva, Israel. PATIENT(S): Forty normogonadotropic, normogonadal men with oligoteratoasthenozoospermia and at least one previous IVF attempt in which fertilization failed or the fertilization rate was <30%. INTERVENTION(S): The men were randomly assigned to treatment with daily injections of 75 IU of FSH or 150 IU of FSH for at least 60 days before IVF treatment. A control group of men underwent an IVF cycle without treatment and then were randomly assigned tojoin group 1A or 1B for an additional IVF cycle with treatment. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels during FSH treatment, evaluation of ultramorphologic changes in sperm by electron microscopy, and comparison of fertilization rates in the control and study groups. RESULT(S): After treatment with 75 IU or 150 IU of FSH, the mean fertilization rates were 19.7% and 20.5%, respectively, compared with a 5.8% fertilization rate in the study control cycles. CONCLUSION(S): Prolonged treatment with FSH results in a significant increase in fertilization rates. This effect may be related to improvements in subcellular components of the sperm.

The effect of betamethasone on fetal biophysical activities and Doppler velocimetry of umbilical and middle cerebral arteries.

OBJECTIVE: Preliminary reports suggest that antenatal steroid administration may confound the assessment of fetal well-being by suppressing biophysical activities, consequently drug-induced effects could prompt unwarranted delivery of premature fetuses. The purpose of this study was to examine the effect of antenatal betamethasone administration on fetal biophysical activities and Doppler flow indices of the umbilical and middle cerebral circulation. METHODS: Forty women at risk of premature delivery between 27-32 weeks gestation (mean 30.2 weeks) received two consecutive doses of intramuscular betamethasone, 24 hours apart. Ultrasonographic observations of fetal behavior for 30 minute periods and Doppler examination of the umbilical and cerebral arteries were performed prior to (0 hours), 48 hours after, and 96 hours after administration of the first dose. To account for fetal circadian rhythms and maternal prandial status, all examinations were carefully timed and performed between 1-4 pm. Analysis of Variance, chi-square test and Fisher's Exact test were used for statistical analysis, as appropriate. RESULTS: Nine patients were excluded from analysis due to delivery prior to completion of all examinations. Number of breathing episodes as well as total breathing time at 48 hours decreased by 83.0% (p<0.01) and 90.4% (p<0.01), respectively, at 48 hours in comparison to baseline. Fetal limb and trunk movements decreased by 53.2% (p<0.01) and 48.6% (p<0.01), respectively. Amniotic fluid volume and fetal tone were normal in all patients. At 48 hours, 14 of 31 fetuses and 4 of 31 fetuses had a biophysical profile score of 6/8 and 4/8, respectively, in comparison to 0 of 31 and 0 of 31 at 0 hours (p<0.05 and p<0.001, respectively). All parameters returned to baseline values at 96 h. Pulsatility indices of umbilical and middle cerebral arteries remained unchanged at 48 hours and 96 hours (p=NS). CONCLUSIONS: Betamethasone induces a profound, albeit transient, suppression of fetal breathing, limb and trunk movements, resulting in decreased biophysical profile scores. Awareness of this drug-induced effect might prevent unnecessary iatrogenic delivery of preterm fetuses.

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, self-limited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), Z = 2.47, (theta = 0.20); D17S40 (pLEW101), Z = 2.15 (theta = 0.15); D17S35 (CRI-pP3-1), Z = 1.78 (theta = 0.15); D17S46 (pLEW108), Z = 1.69 (theta = 0.18), D17S254, Z = 2.30 (theta = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave Z = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a "false positive" (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.