Gabriele Saccone

Prenatal carrier screening has expanded to include a large number of genes offered to all couples considering pregnancy or with an ongoing pregnancy. Expanded carrier screening refers to identification of carriers of single-gene disorders outside of traditional screening guidelines. Expanded carrier screening panels include numerous autosomal recessive and X-linked genetic conditions, including those with a very low carrier frequency, as well as those with mild or incompletely penetrant phenotype. Therefore, the clinical utility of these panels is still subject of debate. Priority should be given to carrier screening panels that include a comprehensive set of severe childhood-onset disorders. Psychosocial support and genetic couseling should be available prior to screening and for the return of positive results. Systems are needed to reduce the risk of misinterpreting results. Finally, attention should be paid on the impact of expanded carrier screening on health care organizations and burden of cost.

INTRODUCTION:
To explore the effect of maternal fluorinated steroid therapy on fetuses affected by second degree immune-mediated atrioventricular block (AVB).

MATERIAL AND METHODS:
Studies reporting the outcome of fetuses with immune-mediated second degree AVB diagnosed on prenatal ultrasound and treated with fluorinated steroids compared to those not treated were included. The primary outcome was the overall progression of AVB to either continuous or intermittent third degree AVB at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used.

RESULTS:
5 studies (71 fetuses) were included. The progression rate to AVB at birth in fetuses treated with steroids was 52% (95% CI 23-79) while in fetuses not receiving steroid therapy was 73% (95% CI 39-94). The overall rate of regression to either first degree, intermittent first/second degree or sinus rhythm in fetuses treated with steroids was 25% (95% CI 12-41) compared to 23% (95% CI 8-44) of those not treated. Stable (constant) second degree AVB at birth was present in 11% (95% CI 2-27) of cases in the treated group and in none of the new-borns in the untreated group, while complete regression to sinus rhythm occurred in 21% (95% CI 6-42) of fetuses receiving steroids versus 9% (95% CI 0-41) of those untreated.

CONCLUSIONS:
There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second degree immune-mediated AVB. This article is protected by copyright. All rights reserved.

OBJECTIVE:
To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester in screening for preterm birth in in vitro (IVF)-conceived twin pregnancies versus spontaneously-conceived twin pregnancies.
METHODS:
This was a retrospective cohort study. Potential study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7 - 23 6/7-week gestation. All women with twin diamniotic pregnancies screened with a singlet TVU CL for this trial were included. Mean TVU CLs were compared between IVF-conceived twin pregnancies and spontaneously-conceived twin pregnancies. The relationship of TVU CL with gestational age at delivery was assessed. Incidence of short TVU CL, defined as TVU CL ≤ 30 mm, was also calculated in the two groups. The primary outcome was the mean of TVU CL. Distribution of CL was determined and normality was examined in both groups
RESULTS:
668 women with diamniotic twin pregnancies who underwent TVU CL screening between 18 0/6 and 23 6/7 weeks were included. 158 (23.7%) were IVF-conceived pregnancies, and 510 (76.3%) were spontaneously-conceived pregnancies. No women received progesterone, pessary, or cerclage for preterm birth prevention during pregnancy. The mean TVU CL was significantly lower in the IVF-conceived group (32.2 ± 10.5 mm) compared to the spontaneously-conceived group (34.1 ± 9.1 mm) (mean difference (MD) -1.90 mm, 95% CI -3.72 to -0.08). The incidence of TVU CL ≤ 30 mm was 30.4% in the IVF-conceived group and 21.6% in the spontaneously-conceived group (adjusted odds ratio (aOR) 1.59, 95% CI 1.06-2.37). IVF-conceived twins had a significantly higher risk of spontaneous preterm birth < 34 weeks (32.9 versus 21.2%; aOR 1.83, 95% confidence interval (CI) 1.23-2.71) and higher rate of delivery due to spontaneous onset of labor (64.5 versus 54.9%; aOR 1.50, 95% CI 1.03-2.17). For any given TVU CL measured between 18 0-7 and 23 6/7 weeks, gestational age at delivery for IVF-conceived twins was earlier by about 1 week on average compared with spontaneously-conceived twins.
CONCLUSION:
The higher rate of spontaneous preterm birth in IVF-conceived twin pregnancies is predicted by lower midtrimester TVU CL, as well as by the lower gestational age at birth per any given CL in the IVF-conceived compared to the spontaneously-conceived twin pregnancies.

OBJECTIVE:
To evaluate the effect of endometriosis on pregnancy outcomes.
DESIGN:
Systematic review and meta-analysis.
SETTING:
Not applicable.
PATIENT(S):
Women with or without endometriosis.
INTERVENTION(S):
Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included.
MEAN OUTCOME MEASURE(S):
Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI).
RESULT(S):
Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia.
CONCLUSION(S):
Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.
Copyright © 2017 American Society for Reproductive Medicine.

BACKGROUND:
A recent large meta-analysis concluded that prior surgical abortion was an independent risk factor for spontaneous preterm birth (PTB), while they found no significant correlation between PTB and medical abortion.
OBJECTIVE:
To evaluate the potential impact of changes in US abortion rates and practices on US incidence of PTB rate.
STUDY DESIGN:
This was an epidemiologic analysis of legal abortion and PTB data in the USA from 2003-2012. Birth data (annual total birth, annual number and incidence of PTB, defined as PTB<37 weeks) are from National Vital Statistics Reports from the National Center for Health Statistics, Center of Disease Control and Prevention (CDC). Abortion data were collected using Abortion Surveillance provided by the CDC. Abortion incidence was reported overall, and by type: surgical, medical method and procedures reported as "other" such as intrauterine instillation and hysterectomy/hysterotomy. To test for the trend of abortion and of PTB over time, we used the chi-squared test for trend. The primary outcome of our study was the correlation trend analysis between abortion rate and PTB rate. Pearson correlation test was used. A two-tailed p value of 0.05 or less was considered significant.
RESULTS:
From 2003 to 2012 there were 41 206 315 births in the USA, of which 5 042 982 (12.2%) were <37 weeks. The PTB rate declined significantly from 12.3% in the 2003 to 11.5% in the 2012 (p-value test for trend <0.04). Out of the 6 122 649 legal abortions, reported by type of procedure, performed from 2003 to 2012 in the USA, 5 132 789 were surgical abortion (82.8%) and 860 288 (14.0%) were medical. Chi-squared test for trend showed that the rate of surgical abortion significantly decreased from 88.9 to 78.0% (p<0.01) while the rate of medical abortion significantly increased from 7.9 to 21.9% (p<0.01). The rate of PTB was correlated with the rate of medical abortion (p=0.01) and of surgical abortion (p=0.02) over time. The higher the surgical abortion rate, the higher the incidence of PTB (Pearson correlation 0.712); the higher medical abortion rate, the lower the incidence of PTB (Pearson correlation -0.731).
CONCLUSION:
Recent changes in abortion practices may be associated with the current decrease in US incidence of PTB. Further study on the effect of surgical versus medical abortion is warranted regarding a possible effect on the incidence of PTB.

INTRODUCTION:
While nausea and vomiting in early pregnancy are very common, affecting approximately 80% of pregnancies, hyperemesis gravidarum is a severe form affecting 0.3-1.0% of pregnancies. Although hyperemesis gravidarum is rarely a source of mortality, it is a significant source of morbidity. It is one of the most common indications for hospitalization in pregnancy. Beyond the maternal and fetal consequences of malnutrition, the severity of hyperemesis symptoms causes a major psychosocial burden leading to depression, anxiety, and even pregnancy termination. The aim of this meta-analysis was to examine all randomized controlled trials of interventions specifically for hyperemesis gravidarum and evaluate them based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs.
MATERIAL AND METHODS:
Randomized controlled trials were identified by searching electronic databases. We included all randomized controlled trials for the treatment of hyperemesis gravidarum. The primary outcome was intervention efficacy as defined by severity, reduction, or cessation in nausea/vomiting; number of episodes of emesis; and days of hospital admission. Secondary outcomes included other measures of intervention efficacy, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs.
RESULTS:
Twenty-five trials (2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. Selected comparisons reported below: No primary outcome data were available when acupuncture was compared with placebo. There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (risk ratio (RR) 1.40, 95% CI 0.79-2.49 and RR 1.51, 95% CI 0.92-2.48, respectively). Midwife-led outpatient care was associated with fewer hours of hospital admission than routine inpatient admission (mean difference (MD) -33.20, 95% CI -46.91 to -19.49) with no difference in pregnancy-unique quantification of emesis and nausea (PUQE) score, decision to terminate the pregnancy, miscarriage, small-for-gestational age infants, or time off work when compared with routine care. Women taking vitamin B6 had a slightly longer hospital stay compared with placebo (MD 0.80 days, 95% CI 0.08-1.52). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40-1.40) or side effects. A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15-3.55, and MD -0.10, 95% CI -1.63-1.43; one study, 83 women, respectively). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23-4.69, and RR 2.38, 95% CI 1.10-5.11, respectively). There were no clear differences between groups for other side effects. In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (risk ratio (RR) 0.70, 95% CI 0.56-0.87, RR 0.48, 95% CI 0.34-0.69, and RR 0.31, 95% CI 0.11-0.90, respectively) There were no clear differences between groups for other important outcomes including quality of life and other side effects.

INTRODUCTION:
Congenital absence of the ductus venosus (ADV) is a rare vascular anomaly often associated with fetal cardiac and extracardiac anomalies, aneuploidies, and hydrops. The prognosis depends on the patterns of abnormal venous circulation, on the associated malformations and on chromosomal aberrations.
METHODS:
We performed a retrospective audit of all consecutive cases with ADV referred in our centres and analysed the outcomes.
RESULTS:
A total of six cases with prenatally diagnosed ADV were identified. The gestational age at diagnosis ranged from 15 to 35 weeks. Karyotyping was performed in all cases. Normal karyotype was found in five out of the six cases. Overall, four neonates survived at 28 days follow-up. The other two died 48 hours after delivery: both of them had extrahepatic ADV.
DISCUSSION:
Absence of the ductus venosus may be compatible with normal fetal development without relevant disturbance of circulation and oxygenation independently from type of abnormal venous circulation.

Objective: To determine if women with preterm superimposed preeclampsia without severe features can be successfully and safely triaged to outpatient management.
MATERIALS AND METHODS:
This was a multicenter, retrospective, cohort study of singleton pregnancies with superimposed preeclampsia without severe features diagnosed before 37 weeks managed outpatient versus inpatient at Thomas Jefferson University (Philadelphia, PA) and at University of Naples (Naples, Italy) from January 2008 to July 2015. The attending physician made the decision to manage outpatient or inpatient at his or her discretion. The primary outcome was composite maternal morbidity defined as development of at least one of the following: severe features, HELLP syndrome, placental abruption, eclampsia, postpartum hemorrhage, intensive care unit admission, or maternal death. Logistic regression, presented as adjusted odds ratio (aOR) with the 95% of confidence interval (CI) was performed.
RESULTS:
A total of 365 women with superimposed preeclampsia without severe features before 37 weeks were analyzed. 198 (54.2%) were managed outpatient, and 167 (45.8%) were managed inpatient. Women managed as outpatients had a similar rate of maternal morbidity compared to those managed as inpatients (36.4% versus 41.3%, aOR 0.82, 95%CI 0.55-1.17). Fetuses from women in the outpatient group had a significantly lower risk of small for gestational age (17.7% versus 29.3%; aOR 0.53, 95%CI 0.30-0.84), and lower risk of admission to neonatal intensive care unit (40.4% versus 47.9%; aOR 0.72, 95%CI 0.39-0.95) compared to women managed as inpatients.
CONCLUSIONS:
Low risk women with superimposed preeclampsia without severe features can be triaged to outpatient management without increased maternal morbidity.

OBJECTIVE:
To examine whether chewing gum hastens the return of gastrointestinal function after a cesarean delivery.
METHODS:
All randomized controlled trials comparing the use of chewing gum in the immediate postoperative recovery period (i.e. intervention group) with a control group were included in the meta-analysis. The primary outcome was the time to first flatus in hours. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI).
RESULTS:
Seventeen trials, including 3041 women, were analyzed. Trials were of moderate to low quality with different inclusion criteria. In most of the included trials chewing gum was given right after delivery, three times a day for 30 min each and until the first flatus. Women who were randomized to the chewing gum group had a significantly lower mean time to first flatus (MD - 6.49 h, 95%CI -8.65 to -4.33), to first bowel sounds (MD - 8.48 h, 95%CI -9.04 to -7.92), less duration of stay (MD - 0.39 days, 95%CI -0.78 to -0.18), lower time to first feces (MD - 9.57 h, 95% CI -10.28 to 8.87) and to the first feeling of hunger (MD - 2.89 h, 95%CI -4.93 to -0.85), less number of episodes of nausea or vomiting (RR 0.33, 95%CI 0.12 to 0.87), less incidence of ileus (RR 0.39, 95%CI 0.19 to 0.80) and significantly higher satisfaction.
CONCLUSIONS:
Gum chewing starting right after cesarean delivery three times a day for about 30 min until the first flatus is associated with early recovery of bowel motility. As this is a simple, generally inexpensive intervention, providers should consider implementing cesarean postoperative care with gum chewing.

OBJECTIVES:
To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in singleton gestations with a second trimester short cervix.
METHODS:
Electronic databases were searched from their inception until February 2016. We included randomized clinical trials (RCTs) comparing the use of the cervical pessary with expectant management in singletons pregnancies with transvaginal ultrasound cervical length (TVU CL) ≤25 mm. The primary outcome was incidence of SPTB <34 weeks. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).
RESULTS:
Three RCTs (n = 1,420) were included. The mean gestational age (GA) at randomization was approximately 22 weeks. The Arabin pessary was used as intervention in all three trials, and was removed by vaginal examination at approximately 37 weeks. Cervical pessary was not associated with prevention of SPTB <37 (20.2% vs 50.2%; RR 0.50, 95% CI 0.23 to 1.09), <34, <32, and <28 weeks, compared to no pessary. No differences were found in the mean of GA at, interval from randomization to delivery, incidence of preterm premature rupture of membranes and of cesarean delivery, and in neonatal outcomes. The Arabin pessary was associated with a significantly higher risk of vaginal discharge.
CONCLUSIONS:
In singleton pregnancies with a TVU CL ≤25mm at 200 -246 weeks, the Arabin pessary does not reduce the rate of spontaneous preterm delivery or improve perinatal outcome. Individual patient data meta-analysis may clarify whether cervical pessary may be beneficial in subgroups, such as only singleton gestations without prior SPTB or by different CL cutoffs.

INTRODUCTION:
Gestational hypertensive disorders, including gestational hypertension and preeclampsia, are one of the leading causes of maternal morbidity and mortality. The aim of our study was to evaluate the effect of exercise during pregnancy on the risk of gestational hypertensive disorders.
MATERIAL AND METHODS:
Electronic databases were searched from their inception to February 2017. Selection criteria included only randomized controlled trials of uncomplicated pregnant women assigned before 23 weeks to an aerobic exercise regimen or not. The summary measures were reported as relative risk with 95% confidence intervals. The primary outcome was the incidence of gestational hypertensive disorders, defined as either gestational hypertension or preeclampsia.
RESULTS:
Seventeen trials, including 5075 pregnant women, were analyzed. Of them, seven contributed data to quantitative meta-analysis for the primary outcome. Women who were randomized in early pregnancy to aerobic exercise for about 30-60 min two to seven times per week had a significant lower incidence of gestational hypertensive disorders (5.9% vs. 8.5%; relative risk 0.70, 95% confidence interval 0.53-0.83; seven studies, 2517 participants), specifically a lower incidence of gestational hypertension (2.5% vs. 4.6%; relative risk 0.54, 95% confidence interval 0.40-0.74; 16 studies, 4641 participants) compared with controls. The incidence of preeclampsia (2.3% vs. 2.8%; relative risk 0.79, 95% confidence interval 0.45-1.38; six studies, 2230 participants) was similar in both groups. The incidence of cesarean delivery was decreased by 16% in the exercise group.
CONCLUSIONS:
Aerobic exercise for about 30-60 min two to seven times per week during pregnancy, as compared with being more sedentary, is associated with a significantly reduced risk of gestational hypertensive disorders overall, gestational hypertension, and cesarean delivery.

OBJECTIVE:
Cervical length screening by transvaginal sonography (TVS) has been shown to be a good predictive test for spontaneous preterm birth (PTB) in symptomatic singleton pregnancy with threatened preterm labor (PTL). The aim of this review and meta-analysis of individual participant data was to evaluate the effect of knowledge of the TVS cervical length (CL) in preventing PTB in singleton pregnancies presenting with threatened PTL.
METHODS:
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (May 2016) and reference lists of retrieved studies. Selection criteria included randomized controlled trials of singleton gestations with threatened PTL randomized to management based mainly on CL screening (intervention group), or CL screening with no knowledge of results or no CL screening (control group). Participants included women with singleton gestations at 23 + 0 to 36 + 6 weeks with threatened PTL. We contacted corresponding authors of included trials to request access to the data and perform a meta-analysis of individual participant data. Data provided by the investigators were merged into a master database constructed specifically for the review. The primary outcome was PTB < 37 weeks. Summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% CI.
RESULTS:
Three trials including a total of 287 singleton gestations with threatened PTL between 24 + 0 and 35 + 6 weeks were included in the meta-analysis, of which 145 were randomized to CL screening with knowledge of results and 142 to no knowledge of CL. Compared with the control group, women who were randomized to the known CL group had a significantly lower rate of PTB < 37 weeks (22.1% vs 34.5%; RR, 0.64 (95% CI, 0.44-0.94); three trials; 287 participants) and a later gestational age at delivery (MD, 0.64 (95% CI, 0.03-1.25) weeks; MD, 4.48 (95% CI, 1.18-8.98) days; three trials; 287 participants). All other outcomes for which there were available data were similar in the two groups.
CONCLUSIONS:
There is a significant association between knowledge of TVS CL and lower incidence of PTB and later gestational age at delivery in symptomatic singleton gestations with threatened PTL. Given that in the meta-analysis we found a significant 36% reduction in the primary outcome, but other outcomes were mostly statistically similar, further study needs to be undertaken to understand better whether the predictive characteristics of CL screening by TVS can be translated into better clinical management and therefore better outcomes and under what circumstances

OBJECTIVE:
To evaluate benefits and harms of food intake during labor.
DATA SOURCES:
Electronic databases such as MEDLINE and ClinicalTrials.gov were searched from their inception until October 2016.
METHODS OF STUDY SELECTION:
We included randomized trials comparing a policy of less-restrictive food intake with a policy of more restrictive food intake during labor. The primary outcome was the mean duration of labor. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of either a relative risk or a mean difference with 95% confidence interval (CI).
TABULATION, INTEGRATION, AND RESULTS:
Ten trials, including 3,982 laboring women, were included. All the studies involved laboring singletons considered at low risk because they had no obstetric or medical complications that would increase the likelihood of cesarean delivery. In three studies, women were allowed to select from a low-residue diet throughout the course of labor. One study had honey date syrup as the allowed food intake. Five studies had carbohydrate drinks as food intake in labor. The last one was the only trial that allowed unrestrictive food intake. In the included studies, all women in the intervention group were allowed the assigned food intake until delivery, whereas women in a control group were allowed only ice chips, water, or sips of water until delivery. A policy of less-restrictive food intake was associated with a significantly shorter duration of labor (mean difference -16 minutes, 95% CI -25 to -7). No other benefits or harms in obstetric or neonatal outcome were noticed. Regurgitation during general anesthesia and Mendelson syndrome did not occur in either group.
CONCLUSION:
Women with low-risk singleton pregnancies who were allowed to eat more freely during labor had a shorter duration of labor. A policy of less-restrictive food intake during labor did not influence other obstetric or neonatal outcomes nor did it increase the incidence of vomiting. Operative delivery rates were similar.

INTRODUCTION:
The National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine have emphasized the need to promote vaginal delivery and have offered recommendations to safely prevent primary cesarean delivery. However, there has been limited discussion regarding management of intravenous fluids and other aspects of labor management that may influence labor. Therefore the aim of our study was to determine if an intravenous fluid rate of 250 vs 125 mL/hour is associated with a difference in cesarean delivery rate MATERIAL AND METHODS: Searches were performed in Medline, OVID, Scopus, ClinicalTrials. gov, the PROSPERO International Prospective Register of Systematic Reviews, Embase, Web of Science, and the Cochrane Library for randomized controlled trials. We included all randomized controlled trials comparing intravenous fluid rates of 125 mL/hour vs. 250 mL/hour in nulliparous women in spontaneous labor at term with singleton pregnancies at ≥ 36 weeks. Studies were included regardless of the type of intravenous fluids used and regardless of whether or not oral intake was restricted during labor. Studies including multiparous women or women whose labor was induced were excluded. The primary outcome was the incidence of cesarean delivery. We planned to assess a sensitivity analysis according to type of fluids used and according to restriction of oral fluid intake RESULTS: Seven trials including 1,215 nulliparous women in spontaneous labor at term were analyzed. 593 (48.8%) were in the 250 mL/hour group, and 622 (51.2%) in the 125 mL/hour group. Five studies used lactated Ringer's solution, one used normal saline in dextrose water, and in one study it was unclear which intravenous fluid was used. Women who received intravenous fluids 250 mL/hour had a significantly lower incidence of cesarean delivery for any indication (12.5% vs 18.1%; RR 0.70, 95% CI 0.53 to 0.92; 7 studies, 1,215 participants; I2 =0%) and for dystocia (4.9% vs 7.7%; RR 0.60, 95% CI 0.38 to 0.97; 5 studies, 1,093 participants; I2 =18%) and a significantly shorter mean of duration of labor of about one hour (mean difference -64.38 minutes, 95% CI -121.88 to -6.88; 6 studies, 1,155 participants; I2 =83%) and of length of second stage of labor (mean difference -2.80 minutes, 95% CI -4.49 to -1.10; 899 participants; I2 =22%) compared to those who received intravenous fluid 125 mL/hour. No differences were found in the other secondary outcomes. There were no maternal or perinatal deaths and only one woman, in the 125 ml/hr group, developed pulmonary edema. The findings persisted regardless of the type of intravenous fluid used. No significant reduction in the incidence of cesarean delivery was demonstrated in women with unrestricted oral intake; however, this was limited to only 2 studies evaluating 254 women CONCLUSIONS: In conclusion, our findings provide evidence that the duration of labor in low-risk nulliparous women may be shortened by a policy of intravenous fluids at a rate of 250 mL/hours rather than 125 mL/hours. This could also lead to a reduction in the incidence of cesarean delivery. The number needed to treat to prevent one cesarean delivery is 18 women. Our data support for increased hydration amongst nulliparous women in labor when oral intake is restricted. Further study is needed regarding risks and benefits of increased hydration among women with unrestricted oral intake, those undergoing induction of labor, and those with medical comorbidities.

OBJECTIVE:
The aim of this systematic review and meta-analysis was to quantify the efficacy of cervical cerclage in preventing preterm birth (PTB) in asymptomatic singleton pregnancies with a mid-trimester short transvaginal ultrasound cervical length (TVU CL) and without prior spontaneous PTB.
METHODS:
Electronic databases were searched from inception of each database until February 2017. No language restrictions were applied. We included all randomized controlled trials (RCTs) of asymptomatic singleton pregnancies without prior spontaneous PTB screened with TVU CL, found to have a midtrimester short CL <25 mm, and then randomized to management with either cerclage (i.e. intervention group) or no cerclage (i.e. control group). We contacted corresponding authors of all the included trials to request access to the data and perform a meta-analysis of individual patient data. Data provided by the investigators were merged into a master database specifically constructed for the review. The primary outcome was PTB <35 weeks. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). The quality of the evidence was assessed using the GRADE approach.
RESULTS:
Five RCTs, including 419 asymptomatic singleton gestations with TVU CL <25 mm and without prior SPTB, were analyzed. No statistically significant differences were found in PTB <35 (21.9% vs 27.7%; RR 0.88, 95% CI 0.63 to 1.23; I2 =0%; 5 studies, 419 participants), <34, <32, <28, and <24 weeks, mean gestational age at delivery, preterm premature rupture of membranes, and neonatal outcomes, comparing women who were randomized in the cerclage group with those who were randomized in the control group, respectively. Planned subgroup analyses revealed a significant decrease in PTB <35 weeks in women with TVU CL <10 mm (39.5% vs 58.0%; RR 0.68, 95% CI 0.47 to 0.98; I2 =0%; 5 studies, 126 participants), in women who received tocolytics (17.5% vs 25.7%; RR 0.61, 95% CI 0.38 to 0.98; I2 =0%; 5 studies, 154 participants), and in those who received antibiotics (18.3% vs 31.5%; RR 0.58, 95% CI 0.33 to 0.98; I2 =0%; 3 studies, 163 participants). The quality of evidence was downgraded two levels because of serious "imprecision" and serious "indirectness," and therefore was judged as low.
CONCLUSIONS:
In women with singleton gestation, without prior spontaneous PTB but with TVU CL <25 mm in the second trimester, cerclage does not prevent preterm delivery or improve neonatal outcome. Cerclage, in singletons without prior spontaneous PTB, seems to be possible efficacious at lower CLs, such as <10 mm, and when tocolytics or antibiotics were used as additional therapy, requiring further studies in these subgroups. Given the low quality of evidence, further well-designed RCT is necessary to confirm the findings of this study.

OBJECTIVE:
To evaluate benefits and harms of food intake during labor.
DATA SOURCES:
Electronic databases such as MEDLINE and ClinicalTrials.gov were searched from their inception until October 2016.
METHODS OF STUDY SELECTION:
We included randomized trials comparing a policy of less-restrictive food intake with a policy of more restrictive food intake during labor. The primary outcome was the mean duration of labor. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of either a relative risk or a mean difference with 95% confidence interval (CI).
TABULATION, INTEGRATION, AND RESULTS:
Ten trials, including 3,982 laboring women, were included. All the studies involved laboring singletons considered at low risk because they had no obstetric or medical complications that would increase the likelihood of cesarean delivery. In three studies, women were allowed to select from a low-residue diet throughout the course of labor. One study had honey date syrup as the allowed food intake. Five studies had carbohydrate drinks as food intake in labor. The last one was the only trial that allowed unrestrictive food intake. In the included studies, all women in the intervention group were allowed the assigned food intake until delivery, whereas women in a control group were allowed only ice chips, water, or sips of water until delivery. A policy of less-restrictive food intake was associated with a significantly shorter duration of labor (mean difference -16 minutes, 95% CI -25 to -7). No other benefits or harms in obstetric or neonatal outcome were noticed. Regurgitation during general anesthesia and Mendelson syndrome did not occur in either group.
CONCLUSION:
Women with low-risk singleton pregnancies who were allowed to eat more freely during labor had a shorter duration of labor. A policy of less-restrictive food intake during labor did not influence other obstetric or neonatal outcomes nor did it increase the incidence of vomiting. Operative delivery rates were similar.

BACKGROUND:
Antiphospholipid syndrome (APS) is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. Anticardiolipin antibodies (aCL), anti-β2 glycoprotein-I (ab2GPI) and lupus anticoagulant (LA) are the main autoantibodies found in APS. Despite the amassed body of clinical knowledge, the risk of obstetric complications associated with specific antibody profile has not been well established.
OBJECTIVE:
To assess the risk of obstetric complications in women with primary APS associated with specific antibody profile
STUDY DESIGN:
The PREGNANTS study is a multicenter, retrospective, cohort study. Diagnosis and classification of APS were based on the 2006 International revised criteria. All women included in the study had at least one clinical criteria for APS, were positive for at least one antiphospholipid antibodies (aCL, ab2GPI and/or LA), and were treated with low-dose aspirin and prophylactic low molecular weight heparin (LMWH) starting from the first trimester. Only singleton pregnancies with primary APS were included. The primary outcome was livebirth, defined as any delivery of a live infant after 22 weeks. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction (IUGR) and stillbirth. We planned to assess the outcomes associated with the various antibody profile (test result for LA, aCL and ab2GPI).
RESULTS:
There were 750 singleton pregnancies with primary APS in the study cohort. 54 (7.2%) were positive for LA only, 458 (61.0%) for aCL only, 128 (17.1%) for ab2GPI only; while 90 (12.0%) were double positive and LA negative and 20 (2.7%) were triple positive. The incidence of livebirth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared to women with only one antibody positive test results, women with multiple antibody positive results had a significantly lower livebirth (40.9% vs 56.6%; aOR 0.71, 95% CI 0.51 to 0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; aOR 1.56, 95% CI 1.22 to 1.95) and with severe features (22.7% vs 13.8%, aOR 1.66, 95% CI 1.19 to 2.49), IUGR (53.6% vs 40.8%; aOR 2.31, 95% CI 1.17 to 2.61) and stillbirth (36.4% vs 21.7%; aOR 2.67, 95% CI 1.22 to 2.94). In women with only one positive test result, women with ab2GPI positivity present alone had a significantly lower livebirth (47.7% vs 56.3% vs 79.6%; p<0.01), and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; p<0.01) and with severe features (17.2% vs 14.4% vs 0%; p=0.02), IUGR (48.4% vs 40.1% vs 25.9%; p<0.01) and stillbirth (29.7% vs 21.2% vs 7.4%; p<0.01) compared to women with aCL and to women with LA present alone, respectively. In the group of women with more than one antibody positivity, triple-positive women had lower livebirth (30% vs 43.3%; aOR 0.69, 95% CI 0.22 to 0.91), and higher incidence of IUGR (70.0% vs 50.0%; aOR 2.40, 95% CI 1.15 to 2.99) compared to double positive and LA negative women.
CONCLUSION:
In singleton pregnancies with primary APS, aCL is the most common sole antiphospholipid antibody present, but ab2GPI is the one associated with the lowest livebirth rate and highest incidence of preeclampsia, IUGR, and stillbirth, compared to presence of aCL or LA alone. Primary APS women have an increased risk of obstetric complications and lower livebirth when more than one antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic LMWH, chance of a live-birth neonate is only 30% for triple-positive women.

OBJECTIVE:
A growing body of evidence suggests that the surgical technique for uterine closure influences uterine scar healing, but there is still no consensus about optimal uterine closure during cesarean delivery (CD). The aim of this systematic review and meta-analysis was to compare the effect of single- versus double-layer closure on the risk of uterine scar defect.
METHODS:
MEDLINE, Scopus, http://ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE and the Cochrane Central Register of Controlled Trials were searched from inception of each database until May 2016. All randomized controlled trials (RCTs) evaluating the effect of single- versus double-layer closure at the time of low transverse cesarean on the risk of uterine scar defect were included. The primary outcome was the incidence of uterine scar defects detected on ultrasound. Secondary outcomes were residual myometrial thickness in mm, evaluated by ultrasound, and incidences of uterine dehiscence and uterine rupture at subsequent pregnancy. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI). For this review the quality of the evidence was assessed using the GRADE approach.
RESULTS:
Nine RCTs (3,696 participants) were included in the meta-analysis. The overall risk of bias of the included trials was low. Statistically heterogeneity within the studies was low with no inconsistency in the primary and secondary outcomes. Women who received single-layer closure had a similar incidence of uterine scar defects (25.5% vs 43.0%; RR 0.77, 95% CI 0.36 to 1.64; 5 trials; 350 participants; low-quality of evidence) compared to women who received double-layer closure. Women who received single-layer closure had a significantly thinner residual myometrial thickness on ultrasound compared to double-layer closure (MD -2.19 mm, 95% CI -2.80 to -1.57; 4 trials; 374 participants; low-quality of evidence). No differences were found in incidence of uterine dehiscence (0.4% vs 0.2%; RR 1.34, 95% CI 0.24 to 4.82; 3 trials; 3,421 participants; low-quality of evidence) or uterine rupture in the subsequent pregnancy (0.1% vs 0.1%; RR 0.52, 95% CI 0.05 to 5.53; 1 trial; 3,234 participants; low-quality of evidence).
CONCLUSIONS:
Single- and double-layer closure of a cesarean uterine incision are associated with similar incidences of uterine scar defect, as well as incidences of uterine dehiscence and uterine rupture in a subsequent pregnancy.

OBJECTIVE:
Cervical length screening by transvaginal ultrasound has been shown to be a good predictive test for spontaneous preterm birth (PTB) in symptomatic singleton pregnancies with threatened preterm labor (PTL). The aim of this Cochrane review and meta-analysis of individual participant data was to evaluate the effect of using knowledge of transvaginal ultrasound cervical length (TVU CL) in preventing PTB in singleton pregnancies presenting with threatened PTL.
METHODS:
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (May 2016) and reference lists of retrieved studies. Selection criteria included randomized controlled trial of singleton gestations with threatened PTL randomized to management based mainly on TVU CL screening (i.e. intervention group) or not (i.e. comparison group). Participants included women with singleton gestations at 23 0/7 to 36 6/7 weeks with threatened PTL. We contacted corresponding authors of all the included trials to request access to the data and perform a meta-analysis of individual participant data. Data provided by the investigators were merged into a master database specifically constructed for the review. The primary outcome was PTB <37 weeks. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI).
RESULTS:
Three trials, including 287 singleton gestations with threatened PTL between 24 0/7 and 35 6/7 weeks, were included in the meta-analysis, of which 145 were randomized to knowledge and 142 to no knowledge of TVU CL. Compared to the control group, women who were randomized to the TVU CL group had a significant decrease in PTB <37weeks (22.1% vs 34.5%; RR 0.64, 95% CI 0.44 to 0.94; 3 trials; 287 participants) and later gestational age at delivery (MD 0.64 weeks, 95% CI 0.03 to 1.25; MD 4.48 days, 95% CI 1.18 to 8.98; 3 trials; 287 participants). All other outcomes for which there were available data were similar in the two groups.
CONCLUSIONS:
There is a significant association between knowledge of TVU CL results and a lower incidence of PTB and later gestational age at delivery in symptomatic singleton gestations with threatened PTL. Given that in the meta-analysis we found a significant 36% reduction in the primary outcome, but other outcomes were mostly statistically similar, further study needs to be undertaken to better understand whether and under what circumstances the predictive characteristics of TVU CL screening can be translated into better clinical management and therefore better outcomes.

Objective: To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained recurrent miscarriage. Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women with a history of unexplained recurrent miscarriage. Intervention(s): Randomized, controlled trials were identified by searching electronic databases. We included randomized, controlled trials comparing supplementation with progestogens (i.e., intervention group) in the first trimester of pregnancy with control (either placebo or no treatment) in women with a history of recurrent miscarriage. All types of progestogens, including natural P and synthetic progestins, were analyzed. Main Outcome Measure(s): The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). Result(s): Ten trials including 1,586 women with recurrent miscarriage were analyzed. Eight studies used placebo as control and were double-blind. Regarding the intervention, two RCTs used natural P, whereas the other eight studies used progestins: medroxyprogesterone, cyclopentylenol ether of progesterone, dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10 trials showed that women with a history of unexplained recurrent miscarriage who were randomized to the progestogens group in the first trimester and before 16 weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53–0.97) and higher live birth rate (RR 1.07, 95% CI 1.02–1.15) compared with those who did not. No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71–1.66), neonatal mortality (RR 1.80, 95% CI 0.44–7.34), and fetal genital abnormalities (RR 1.68, 95% CI 0.22–12.62). Conclusion(s): Our findings provide evidence that supplementation with progestogens may reduce the incidence of recurrent miscarriages and seem to be safe for the fetuses. Synthetic progestogens, including weekly IM 17-hydroxyprogesterone caproate, but not natural P, were associated with a lower risk of recurrent miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progestogen therapy. Further head-to-head trials of P types, dosing, and route of administration are required. (Fertil Steril Ò 2016;-:-–-. Discuss: You can discuss this article with its authors and with other ASRM members at

Recently, a meta-analysis, including 26,526 laboring vertex singletons at term, summarized all available level-1 data from six high-quality randomized clinical trials on the use of ST analysis (STAN) during labor as an adjunct to conventional intrapartum fetal heart rate monitoring. The meta-analysis showed that STAN did not improve perinatal outcomes or decrease cesarean deliveries. Nonetheless there are still reasons to believe STAN may have a role in the future research on intrapartum fetal monitoring. Out of six trials included in the meta-analysis, two included all cephalic singletons in labor, and four enrolled only high-risk pregnant women. This combination of both low- and high-risk populations may have distorted the potential impact of STAN. The test for heterogeneity between both subgroups was found to be statistically significant, indicating that the effect of STAN was different in high-risk women compared to a combination of both low- and high-risk women. Furthermore, the classifications of the fetal heart rate patterns used in the included randomized trials were different. Last but not least, despite >26,000 women with singleton gestations were included in the meta-analysis, the evidence still suffers from a lack of power, especially for subgroup analyses. In summary, while the level-1 data so far indicate overall no perinatal benefit of adding STAN to conventional intrapartum fetal heart rate monitoring for the outcomes most of interest, several issues point to the fact that more research is needed before the STAN technology can be deemed of no value for fetal monitoring in labor.

OBJECTIVE:
To evaluate the effectiveness of antenatal corticosteroids given at ≥34 weeks' gestation.
DESIGN:
Systematic review with meta-analysis.
DATA SOURCES:
Electronic databases were searched from their inception to February 2016.
ELIGIBILITY CRITERIA FOR STUDY SELECTION:
Randomized clinical trials comparing antenatal corticosteroids with placebo or no treatment in women with a singleton pregnancy at ≥34 weeks' gestation. Trials on antenatal steroids in women expected to deliver late preterm (340-366 weeks) and trials given before planned cesarean delivery at term (≥37 weeks) were included.
DATA SYNTHESIS:
The primary outcome was the incidence of severe respiratory distress syndrome (RDS). The summary measures were reported as relative risks or mean differences with 95% confidence intervals.
RESULTS:
Six trials, including 5698 singleton pregnancies, were analyzed. Three included 3200 women at 340-366 weeks' gestation and at risk of imminent premature delivery at the time of hospital admission. The three other trials included 2498 women undergoing planned cesarean delivery at ≥37 weeks. Overall, infants of mothers who received antenatal corticosteroids at ≥34 weeks had a significantly lower risk of RDS (relative risk 0.74, 95% confidence interval 0.61 to 0.91), mild RDS (0.67, 0.46 to 0.96), moderate RDS (0.39, 0.18 to 0.89), transient tachypnea of the newborn (0.56, 0.37 to 0.86), severe RDS (0.55, 0.33 to 0.91), use of surfactant, and mechanical ventilation, and a significantly lower time receiving oxygen (mean difference -2.06 hours, 95% confidence interval -2.17 to -1.95), lower maximum inspired oxygen concentration (-0.66%, -0.69% to -0.63%), shorter stay on a neonatal intensive care unit (-7.64 days, -7.65 to -7.64), and higher APGAR scores compared with controls. Infants of mothers who received antenatal betamethasone at 340-366 weeks' gestation had a significantly lower incidence of transient tachypnea of the newborn (relative risk 0.72, 95% confidence interval 0.56 to 0.92), severe RDS (0.60, 0.33 to 0.94), and use of surfactant (0.61, 0.38 to 0.99). Infants of mothers undergoing planned cesarean delivery at ≥37 weeks' gestation who received prophylactic antenatal corticosteroids 48 hours before delivery had a significantly lower risk of RDS (0.40, 0.27 to 0.59), mild RDS (0.43, 0.26 to 0.72), moderate RDS (0.40, 0.18 to 0.88), transient tachypnea of the newborn (0.38, 0.25 to 0.57), and mechanical ventilation (0.19, 0.08 to 0.43), and significantly less time receiving oxygen (mean difference -2.06 hours, 95% confidence interval -2.17 to -1.95), lower percentage of maximum inspired oxygen concentration (-0.66%, -0.69% to -0.63%), shorter stay in neonatal intensive care (-7.44 days, -7.44 to -7.43), and a higher APGAR score at one and at five minutes.
CONCLUSIONS:
Antenatal steroids at ≥34 weeks' gestation reduce neonatal respiratory morbidity. A single course of corticosteroids can be considered for women at risk of imminent late premature delivery 340-366 weeks' gestation, as well as for women undergoing planned cesarean delivery at ≥37 weeks' gestation.

BACKGROUND:
Preterm birth (PTB) is the major cause of perinatal mortality in the United States. In the past, pregnant women have been recommended against exercise because of presumed risks of PTB. Physical activity has been theoretically related to PTB as it increases the release catecholamines, especially norepinephrine, which might stimulate myometrial activity. Conversely, exercise may reduce the risk of PTB by other mechanisms such as decreased oxidative stress or improved placenta vascularization. Therefore, the safety of exercise regarding PTB and its effects on gestational age at delivery remain controversial.
OBJECTIVE:
To evaluate the effects of exercise during pregnancy on the risk of PTB.
DATA SOURCES:
MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from the inception of each database to April 2016.
METHODS OF STUDY SELECTION:
Selection criteria included only randomized clinical trials (RCTs) of pregnant women randomized before 23 weeks to an aerobic exercise regimen or not. Types of participants included women mainly of normal weight with uncomplicated, singleton pregnancies without any obstetric contraindication to physical activity. The summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% confidence intervals (CI). The primary outcome was the incidence of PTB <37weeks.
TABULATION, INTEGRATION, AND RESULTS:
Of the 2,059 women included in the meta-analysis, 1,022 (49.6%) were randomized to the exercise group and 1,037 (50.4%) to the control group. Aerobic exercise lasted about 35-90 minutes 3-4 times per week. Women who were randomized to aerobic exercise had a similar incidence of PTB<37 weeks (4.5% vs 4.4%; RR 1.01, 95% CI 0.68-1.50) and a similar mean gestational age at delivery (MD 0.05 week, 95% CI - 0.07 to 0.17) compared to controls. Women in the exercise group had a significantly higher incidence of vaginal delivery (73.6% vs 67.5%; RR 1.09, 95% CI 1.04-1.15) and significantly lower incidence of cesarean delivery (17.9% vs 22%; RR 0.82, 95% CI 0.69-0.97) compared to controls. The incidence of operative vaginal delivery (12.9% vs 16.5%; RR 0.78, 95% CI 0.61-1.01) was similar in both groups. Women in the exercise group had a significantly lower incidence of gestational diabetes mellitus (2.4% vs 5.9%; RR 0.41, 95% CI 0.24-0.68) and significantly lower incidence of hypertensive disorders (1.9% vs 5.1%; RR 0.36, 95% CI 0.19-0.69) compared to controls. No differences in low birth weight (5.2% vs 4.7%; RR 1.11, 95% CI 0.72-1.73) and mean birth weight (MD -10.46 grams, 95% CI -47.10 to 26.21) between exercise group and controls were found.
CONCLUSION:
Aerobic exercise for 35-90 minutes 3-4 times per week during pregnancy can be safely performed by normal-weight women with singleton, uncomplicated gestations, as this is not associated with an increased risk of PTB or with a reduction in mean gestational age at delivery. Exercise was associated with a significantly higher incidence of vaginal delivery and a significantly lower incidence of cesarean delivery, with a significantly lower incidence of gestational diabetes mellitus and hypertensive disorders, and therefore should be encouraged.

BACKGROUND:
Depression is a prevalent condition in pregnancy affecting about 10% of women. Maternal depression has been associated with an increase in preterm births (PTB), low birthweight and fetal growth restriction, and postnatal complications. Available treatments for depressive disorders are psychotherapeutic interventions and antidepressant medications including selective serotonin inhibitors (SSRIs). SSRI use during pregnancy has been associated with several fetal and neonatal complications; so far, however, the risk of PTB in women using SSRIs during pregnancy is still a subject of debate.
OBJECTIVE:
To evaluate the risk of preterm birth (PTB) in cases of exposure to SSRIs during pregnancy.
SEARCH STRATEGY:
Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE and the Cochrane Central Register of Controlled Trials) were searched from their inception until May 2015 with the use of a combination of the following text words 'depression', 'pregnancy', 'exposure', 'antidepressant', 'SSRI', 'selective serotonin reuptake inhibitor', 'preterm birth', 'small for gestational age' and 'prematurity'.
SELECTION CRITERIA:
We included studies evaluating the effect of SSRIs exposure in utero and pregnancy outcomes. All cohort and case-control studies were eligible to be included if they reported the incidence of PTB after any exposure to SSRIs and had a comparison group of unexposed pregnant women. Studies without a control group were excluded.
DATA COLLECTION AND ANALYSIS:
The primary outcome was the incidence of PTB <37 weeks. Subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy were planned.
MAIN RESULTS:
Eight studies (1 237 669 women) were included: 93 982 in the exposure group and 1 143 687 in the control group. After adjusting for confounders, the incidence of PTB was significantly higher in the group of women treated with SSRIs compared with controls (i.e. both women with depression but without SSRI exposure and women without depression) (adjusted OR (aOR) 1.24, 95% CI 1.09-1.41). In the subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy, an increased risk of PTB (6.8 versus 5.8%; OR 1.17, 95% CI 1.10-1.25) in the SSRI group was found compared with controls (i.e. depressed women treated with psychotherapy alone).
CONCLUSIONS:
Women who received SSRIs during pregnancy had a significantly higher risk of developing PTB compared with controls. This higher risk remained significant even when comparing depressed women on SSRI with women not on SSRI.
TWEETABLE ABSTRACT:
Selective serotonin reuptake inhibitors may be associated with preterm birth.

OBJECTIVE:
To evaluate the risk of preeclampsia in pregnant women with human immunodeficiency virus (HIV).
METHODS:
This is a 26-year population-based retrospective cohort study. Human immunodeficiency virus-infected pregnant women were compared with a HIV-negative comparison group. The primary outcome was the incidence of preeclampsia. We planned subgroup analysis according to antiretroviral therapy.
RESULTS:
A total of 84,725 women were included in the analysis, of whom 453 were HIV-infected and 84,272 HIV-negative. Of the 453 HIV-infected women, 301 (66.4%) received highly active antiretroviral therapy (HAART group) during pregnancy, whereas 152 (33.6%) did not. After adjusting for confounders, we found that HIV-infected women had a significantly higher risk of preeclampsia (10.2% compared with 4.1%; adjusted odds ratio [OR] 2.68, 95% confidence interval [CI] 1.96-3.64), preeclampsia with severe features (4.0% compared with 2.0%; adjusted OR 2.03, 95% CI 1.26-3.28), early-onset (3.5% compared with 1.4%; adjusted OR 2.50, 95% CI 1.51-4.15) and late-onset preeclampsia (6.6% compared with 2.6%; adjusted OR 2.64, 95% CI 1.82-3.85), and preterm birth at less than 37 weeks of gestation (11.0% compared with 4.7%; adjusted OR 2.50, 95% CI 1.86-3.37) compared with the comparison group. Human immunodeficiency virus-infected women who received HAART had a significantly higher risk of preeclampsia compared with women without HIV (13.0% compared with 4.1%; adjusted OR 3.52, 95% CI 2.51-4.94) and compared with the non-HAART group (13.0% compared with 4.6%; adjusted OR 3.08, 95% CI 1.34-5.07). The non-HAART group had a similar risk compared with women without HIV (4.6% compared with 4.1%; adjusted OR 1.14, 95% CI 0.53-2.44).
CONCLUSION:
Human immunodeficiency virus-infected women had an increased risk of preeclampsia. Some of this risk seems to be linked to HAART.