Outcomes and management of pregnancy and puerperal group A streptococcal infections: A systematic review.

INTRODUCTION: Group A streptococcus (Streptococcus pyogenes) is one of the most lethal bacterial pathogens of humans, with increased risk of progression to septic shock and multiorgan failure in the pregnant population. The objective of this study is to systematically review the outcomes and management strategies for pregnancy and puerperal group A streptococcus infections in an effort to provide further guidance for prevention and treatment of a rare but lethal infection worldwide. MATERIAL AND METHODS: A comprehensive search using puerperium and streptococcus pyogenes terms was completed across several registered databases. A total of 902 articles investigating pregnancy and puerperal group A streptococcus infection were identified, with 40 studies fulfilling inclusion criteria of original research articles in humans published from 1990 onwards reporting four or more unique cases of group A streptococcus in pregnancy or postpartum. This study was registered in PROSPERO: CRD42020198983. RESULTS: A total of 1160 patients with pregnancy and puerperal group A streptococcus infection were identified. Most infections occurred postpartum (91.9%), with 4.7% reported antepartum and 0.6% intrapartum. Bacteremia was present in 49.0% of patients and endometritis in 45.9%. Puerperal sepsis was described in 28.2% of cases and progressed to streptococcal toxic shock syndrome in one-third of such cases. Overall, the case fatality ratio was 2.0%, with one-third of the deaths from antenatal cases including 3/22 (13.6%) cases of septic abortion and 10/46 (21.7%) antenatal cases of group A streptococcus infection. CONCLUSIONS: Group A streptococcus infection remains an important contributor to pregnancy and puerperal morbidity and mortality. Early recognition, diagnosis and aggressive management are important for favorable outcomes given the serious risk of sepsis and streptococcal toxic shock syndrome.

Amnioreduction with rescue cerclage at advanced cervical dilation or gestational age.

OBJECTIVE: To determine the feasibility of rescue cerclage and amnioreduction at advanced cervical dilation or gestational age. METHODS: We present a retrospective case series of women who underwent rescue cerclage at either an advanced gestational age (24 + 0 to 24 + 6 weeks) or cervical dilation (≥4 cm), with a subset undergoing amnioreduction prior to cerclage placement. RESULTS: Nine women were included and amnioreduction was performed in 7 (78%). A bi-modal distribution of obstetric outcomes was observed, with 5 (56%) women delivering ≥34 weeks gestation, 3 (33%) of which delivered at term. Two (22%) women experienced intra-operative rupture of membranes and subsequent perinatal deaths. Two (22%) women delivered extremely premature, with one resulting in infant death. DISCUSSION: Our data show that rescue cerclage with amnioreduction may be successful at advanced gestational ages or cervical dilations, suggesting that these women should be included in prospective studies to better establish the efficacy and safety of this procedure.

Association between hypertensive disorders and fetal growth restriction in twin compared with singleton gestations.

BACKGROUND: Hypertensive disorders of pregnancy (including preeclampsia or gestational hypertension) are associated with fetal growth restriction in singleton pregnancies, an association that may be attributed to abnormal placentation as the shared etiology between these conditions. Given that the pathogenesis of these conditions in twin pregnancies may involve mechanisms other than abnormal placentation, it is unclear whether a similar association between hypertensive disorders of pregnancy and fetal growth restriction is present in twins. Data on the relationship between hypertensive disorders of pregnancy and fetal growth restriction in twins are limited and conflicting. This controversy may be attributed to limitations of existing studies including the use of a singleton-based birthweight reference to define fetal growth restriction in twins and the lack of a positive control group of singleton gestations. OBJECTIVE: The objective of the study was to determine the association between hypertensive disorders of pregnancy and fetal growth restriction in dichorionic twin gestations, using both a singleton- and a twin-based birthweight reference, and to compare this association with that observed in singleton gestations. STUDY DESIGN: We performed a retrospective cohort study of all women with dichorionic twin or singleton gestations giving birth in a single tertiary center during 2003-2015. Fetal growth restriction was defined in separate analyses as birthweight <10th percentile for gestational age using either a singleton- or a twin-based birthweight reference. The association between hypertensive disorders of pregnancy and fetal growth restriction was determined separately for twin and singleton gestations and was expressed as adjusted relative risk with 95% confidence interval. RESULTS: A total of 1520 twin and 48,943 singleton gestations were included. In singleton gestations, hypertensive disorders of pregnancy were associated with an increased risk of fetal growth restriction (16.6% vs 7.4%, adjusted relative risk, 2.07, 95% confidence interval, 1.87-2.30). In twins, there was no association between hypertensive disorders of pregnancy and fetal growth restriction when a singleton-based reference was used to define fetal growth restriction. However, when using a twin-based reference to define fetal growth restriction, hypertensive disorders of pregnancy in twin gestations were associated with a similar increase in the risk of fetal growth restriction to that seen in singletons (11.8% vs 4.7%, adjusted relative risk, 2.37, 95% confidence interval, 1.69-3.34). Findings were similar with regard to the reverse association between fetal growth restriction and hypertensive disorders of pregnancy: in women with twin gestations, the increase in the risk of hypertensive disorders of pregnancy in pregnancies complicated by fetal growth restriction of 1 twin was similar to that observed in singletons only when a twin-based reference was used to define fetal growth restriction (twins: 21.3% vs 9.8%, adjusted relative risk, 2.15, 95% confidence interval, 1.63-3.06; singletons: 8.8% vs 3.7%, adjusted relative risk, 2.19, 95% confidence interval, 1.95-2.44). CONCLUSION: The association between hypertensive disorders of pregnancy and fetal growth restriction in dichorionic twins is similar in magnitude to that observed in singletons so long as appropriate birthweight references are applied. Therefore, women with a twin gestation complicated by one of these conditions should be closely monitored for the other. Our findings suggest that the use of a twin-based reference to diagnose fetal growth restriction in twin gestations may be more informative and clinically relevant than using a singleton-based reference.

Male sex bias in placental dysfunction.

Several reports suggest a male fetal preponderance in a variety of complications of pregnancy attributable to severe placental dysfunction (SPD). However, the underlying mechanisms remain unknown. Our primary objective was to explore the relationship between fetal sex and the spectrum of conditions implicated in abnormal placentation. We identified singleton pregnancies with a fetus delivered between 20 + 0 and 32 + 6 weeks of gestation with one or more pregnancy complications attributed to SPD (severe pre-eclampsia, intra-uterine fetal death, intra-uterine growth restriction, abnormal Doppler studies, abruption) at a single institution between 1999 and 2007. Pedigrees of index cases were created to define the relationship between fetal sex and the risk of SPD. We identified 132 index cases, 97/132 (73%) were male. Eighty-four index cases had a total of 133 sibs, of which 37/133 (28%) were affected with SPD (22 male, 15 female). A male sex preponderance persisted across all manifestations of PD in index cases with sibs. In families with the absence of maternal chronic hypertension (cHTN; n = 70), the index case was 5.9 (95% CI 2.28-16.15; P <0.001) times more likely to be male and most (12/14) affected sibs of male index cases were male, while female index cases had no affected sibs. Our results confirm a male fetal sex preponderance in SPD. In a subgroup analysis of families without cHTN, a significant male bias was found to extend to sibs of index cases. This suggests a potential genetic mechanism predisposing the male fetus to abnormal placental development.

Utility of head/abdomen circumference ratio in the evaluation of severe early-onset intrauterine growth restriction.

OBJECTIVE: To determine whether the predominant phenotype of intrauterine growth restriction (IUGR) is symmetric or asymmetric in severe, early-onset disease due to placental insufficiency. METHODS: We conducted a retrospective chart review of high-risk pregnant women with severe, early-onset IUGR who were delivering at < 33+0 weeks' gestation at Mount Sinai Hospital from 2001 to 2010. Ultrasound images were reviewed for fetal biometry, amniotic fluid volume, and uterine and umbilical Doppler flow studies within seven days of delivery, and the frequency of head circumference/abdominal circumference ratio ≥ 95th percentile for gestation was determined. RESULTS: Sixty-two of 107 pregnancies (58%) with early-onset IUGR had an elevated HC/AC ratio (≥ 95th percentile), which was more than 10-fold greater than the expected proportion (P < 0.001). High rates of severe preeclampsia (53%), abnormal amniotic fluid (70%), and abnormal uterine artery Doppler studies (78%) indicated placental insufficiency. CONCLUSION: Fetuses with severe placental IUGR in the second trimester are more likely to have an asymmetric phenotype. This is in contrast to the current belief that asymmetric IUGR is confined to third trimester IUGR.

Hypospadias in males with intrauterine growth restriction due to placental insufficiency: the placental role in the embryogenesis of male external genitalia.

Our aim was to define the association between early onset intra-uterine growth restriction (IUGR) due to placental insufficiency and hypospadias in males. We prospectively studied a cohort of small-for-gestational age (SGA) male infants with hypospadias managed by a multidisciplinary team over a 5-year period. Thirty SGA male infants were diagnosed with hypospadias/abnormal genitalia after birth, and four of them were diagnosed antenatally. Five cases occurred in the smaller pair of discordant IUGR twins, where the larger co-twin had normal male genitalia. Serial ultrasounds demonstrated features of early-onset IUGR in all cases at a median gestational age of 21 weeks (range 14-31weeks). Twenty-one (70%) pregnancies were subsequently complicated by absent/reversed end-diastolic flow in the umbilical arteries indicating severe IUGR, and 17 (57%) women developed severe pre-eclampsia. There were 27 (90%) live births at a median gestational age of 31 weeks (range 27-37); 23 (77%) of the neonates had birth weights <3rd centile. All newborns had normal male karyotypes. In 62% (18/29) the hypospadias was severe. A correlation was found between the severity of the IUGR and the severity of hypospadias as significantly more infants with severe hypospadias were less than the 3rd centile compared to the mild-moderate hypospadias group: 94% (17/18) versus 55% (6/11), respectively (P = 0.02). In conclusion, SGA male newborns with hypospadias exhibit a high rate of early-onset severe IUGR due to placental insufficiency. Early placental development likely influences male external genitalia formation. Careful sonographic evaluation of the genitalia is advised when early-onset placentally mediated IUGR is found.