Wendy L. Kinzler

Fetal growth restriction : a modern approach

Purpose of review Fetal growth restriction is a complicated perinatal condition, with multiple causes. It shares common pathophysiologies with other important disorders, such as preeclampsia and abruption. As a group, these conditions associated with ischemic placental disease are responsible for a large percentage of indicated preterm births. The ability to accurately predict, diagnose and manage these pregnancies has significant and far-reaching implications, including potential effects on long-term adult health. Recent findings Placental ischemia is the most common cause of fetal growth restriction. Alterations in placental development are being linked to various angiogenic mediators, which may be of future use in early risk-determination. Until then, the use of ultrasound to accurately diagnose fetal growth restriction and time delivery is the mainstay of management. Research in this area has revealed some commonalities in the deterioration of the growth restricted fetus, but has also indicated that not every affected fetus will follow the same progression in Doppler and other wellbeing parameters. Most importantly, gestational age at delivery is consistently being documented as a critical factor in perinatal morbidity and mortality. Summary Fetal growth restriction is a late manifestation of early abnormal placental development. Once abnormal Doppler velocimetry is present, surveillance and timing of delivery should be based on the antepartum test results and on the gestational age.

Medical and Economic Effects of Twin Gestations

Objective: To determine the incidence and trends of twinning in the United States and to review the medical and economic effects of twin versus singleton gestations. Methods: Pertinent and recent studies on twin gestations were obtained through a MEDLINE database search of the English language between December 1987 and December 1999. Data from the 1995-1996 National Center for Health Statistics were also used to compare gestational age at delivery, fetal growth restriction, and perinatal mortality for twin and singleton gestations. Studies that have evaluated perinatal risks in relation to advanced reproductive technology also were reviewed and summarized. The economic implications of twinning from a societal perspective and infant quality of life issues of twins compared with singleton gestations are reviewed. Results: Due to delayed childbearing and increased use of reproductive technologies, the incidence of twin gestations in the United States has been increasing. Twin pregnancies have a higher risk of complications, including pregnancy-induced hypertension, anemia, antepartum and postpartum hemorrhage, and maternal mortality. In addition, twin infants are more likely to deliver preterm, have low birth weight and greater perinatal mortality rates. These outcomes influence health care costs and quality of life for both parents and children. Conclusions: Women carrying twin fetuses are at increased risk for perinatal and obstetric complications. The increased perinatal risks that accompany twin fetuses may be partly due to the increasing use of advanced reproductive technologies. The economic burdens, as well as the potential for decreased quality of life among twins, needs careful evaluation.

Perinatal mortality in first- and second-born twins in the United States

OBJECTIVE: To evaluate the prevailing mortality paradox that second-born twins are at higher risk of perinatal mortality than first-born twins. METHODS: We used the 1995–1997 United States “matched multiple birth” data files assembled by the National Center for Health Statistics, for analysis of risk of perinatal mortality in first- and second-born twins (293,788 fetuses). Perinatal mortality was defined to include stillbirths after 20 weeks of gestation and neonatal deaths (deaths within the first 28 days). Gestational age-specific risk of perinatal mortality (per 1,000 total births), stillbirth (per 1,000 total births), and neonatal mortality (per 1,000 livebirths) by order of twin birth were based on the fetuses-at-risk approach. Associations between order of birth and mortality indices were evaluated by fitting multivariable logistic regression models based on the method of generalized estimating equations. These models were adjusted for several potential confounding factors. RESULTS: Perinatal mortality was 37% higher in second-born (26.1 per 1,000 total births) than in first-born (20.3 per 1,000 total births) twins (adjusted relative risk [RR] 1.37; 95% confidence interval [CI] 1.32, 1.42). The increased risk of perinatal mortality in second-born twins was chiefly driven by a 2.46-fold (95% CI 2.29, 2.63) increase in the number of stillbirths. However, the risk of neonatal mortality was very similar between first- and second-born twins (RR 0.99, 95% CI 0.95, 1.04). CONCLUSIONS: The increased risk of perinatal death in second-born twins is driven chiefly by increased rates of stillborn second twins. Thus, the increased mortality in second-born over first-born twins probably is an artifact of mortality comparisons. LEVEL OF EVIDENCE: II-2

Twin deliveries in the United States over three decades: an age-period-cohort analysis.

OBJECTIVE: Time is an important variable in understanding the recent increase in twin deliveries in the United States. Therefore, this study was designed to estimate the influences of maternal age, period (year) of delivery, and maternal-birth-year cohort on trends in rates of twin deliveries. METHODS: United States natality data were used to assess trends in twin pregnancies resulting in live births. This age-period-cohort analysis included 7, 5-year maternal-age groups (15–19 through 45–49 years), 6 twin delivery periods (1975, 1980, 1985, 1990, 1995, and 2000), and 12, 5-year maternal birth cohorts (1926–1930 through 1981–1985). The independent effects of maternal age, twin delivery period, and maternal birth cohort on twin delivery rates for blacks and whites were modeled using Poisson regression techniques. RESULTS: Our study assessed 95,042 blacks and 401,989 whites with twin deliveries. Twin deliveries increased by 46% for blacks and 62% for whites from 1975 to 2000, with the largest increase occurring in the year 2000. For blacks, maternal age had the strongest impact on the increasing twin delivery rates, followed by period of delivery. For whites, the greatest effect was due to period of delivery, followed by maternal birth year cohort and, lastly, maternal age. CONCLUSION: Our data confirm the importance of natures biologic contribution of maternal aging to twin delivery rates, but suggest that recent changes in the environment surrounding pregnancy (nurture) also influence twin delivery rates. The relative contributions of biologic versus environmental influences appear to differ among blacks and whites. LEVEL OF EVIDENCE: II-2

A clinicohistopathologic comparison between HELLP syndrome and severe preeclampsia.

OBJECTIVE To determine whether differences in the clinical entities of HELLP syndrome and severe preeclampsia are associated with different placental lesions. STUDY DESIGN This was a case control study of singleton pregnancies with HELLP syndrome or severe preeclampsia. Archived pathology slides were retrieved and reviewed. Clinical and histopathological features were compared between the two groups. RESULTS There were 31 women with HELLP syndrome and 56 with severe preeclampsia. HELLP syndrome was associated with epigastric pain and higher levels of LDH, bilirubin, liver enzymes and fibrin degradation products. Hemoglobin, hematocrit and platelet counts were lower. Abruption lesions of the placenta were less common with HELLP syndrome (Odds Ratio 0.1 95% Confidence Interval 0.01,0.8). None of the other 22 placental features examined were different between the two conditions. CONCLUSION The significant overlap between HELLP syndrome and severe preeclampsia for both clinical and placental features suggests that the two conditions represent a spectrum of essentially the same pathophysiologic process.

Practice patterns in the timing of antenatal corticosteroids for fetal lung maturity

Abstract Objective: To determine the practice patterns of antenatal corticosteroid (AS) administration in women with threatened preterm labor. Methods: This was a retrospective cohort of patients who received betamethasone between 2009 and 2010, identified through a pharmacy database. Patients with high order multiples; incomplete records and indicated preterm delivery were excluded. Demographic and obstetrical factors were compared between women with an AS to delivery latency of ≤7 days versus >7 days. Parametric and non-parametric tests were used as appropriate. p < 0.05 denotes statistical significance; relative risks with 95% confidence intervals were calculated. Results: Three-hundred forty-five patients were included. Sixty-eight patients (20%) received AS within 7 days of delivery. Women who received AS ≤7 days before delivery (optimal timing) were more likely to have a transvaginal cervical length ≤2 cm (RR:2.53, CI: 1.2–5.6), cervical dilation ≥2 cm (RR: 3.86, CI: 2.7–5.6) and positive fFN (RR: 2.59, CI: 1.1–6.3). Preterm premature ruptured membranes were also associated with optimal timing of AS (RR: 4.86, CI: 3.4–6.8). Conclusions: Eighty percent of patients receive suboptimal timing of AS administration. Factors associated with suboptimal timing are: cervical length >2 cm, cervical dilation <2 cm and negative fFN. Cervical assessment should be a key factor in the decision for AS administration. More research is needed for accurate timing of AS in women with threatened preterm labor.

Noninvasive Ultrasound Assessment of Maternal Vascular Reactivity During Pregnancy: A Longitudinal Study

OBJECTIVE: To estimate the pattern of maternal vascular reactivity in normal and high-risk pregnancies using postocclusion brachial artery diameter. METHODS: Prospective, longitudinal study of 44 low-risk singleton pregnancies and 28 high-risk pregnancies, defined as pregestational diabetes (n = 7), chronic hypertension (n = 4), twin gestation (n = 6), and a previous history of preeclampsia, fetal growth restriction, or vascular disease (n = 11). During each trimester, the brachial artery was ultrasonographically imaged above the antecubital crease. Brachial artery diameter was measured and then occluded for 5 minutes using an inflated blood pressure cuff. Changes in brachial artery diameter at 1 minute after occlusion were expressed as percent change from baseline and were compared across trimesters for both low-risk and high-risk groups, adjusting for potential confounders. RESULTS: Brachial artery diameters were increased after occlusion in every trimester for all groups. For low-risk women, the degree of postocclusion brachial artery dilatation was similar in the first and second trimesters, but was lower in the third trimester. In the first trimester, low-risk women had significantly greater brachial artery diameter increases at 1 minute compared with high-risk singleton pregnancies (19% compared with 12%; P < .001). Compared with low-risk women, pregnancies complicated by pregestational diabetes or chronic hypertension had significantly smaller 1-minute brachial artery diameter changes in the first trimester (7.0 ± 0.5%, P < .001), whereas twin gestations had greater brachial artery responses (22.9 ± 6.0%, P < .001). Women with previous preeclampsia or vascular disease had responses similar to low-risk women. CONCLUSION: Maternal vascular reactivity as assessed by postocclusion brachial artery dilatation decreases in the third trimester in both low-risk and high-risk women. In addition, singleton pregnancies at high risk for preeclampsia display decreased brachial artery reactivity compared with low-risk women. LEVEL OF EVIDENCE: II-3

Variables that underlie cost efficacy of prenatal screening.

As genetic research and technology continues to expand, carrier testing for an increasing number of single gene disorders is becoming available. Tay-Sachs disease and cystic fibrosis are two common recessive conditions with large-scale health implications. Tay-Sachs disease was the first genetic disorder for which community-based screening efforts were utilized and has provided a foundation for the development of other screening programs. Cystic fibrosis testing, on the other hand, has additional complexities and the implementation of population-based screening has been under debate. The many issues (technical, educational, social, psychological and economical) which must be considered as preconceptional and prenatal genetic screening is incorporated into clinical practice are discussed here in the context of Tay-Sachs disease and cystic fibrosis.

Second-trimester cervical pregnancy presenting as a failed labor induction

A 44-year-old woman, gravida 4, para 0–0–3–0, presented at 19 weeks’ gestation with cervical dilatation without contractions or vaginal bleeding. The cervix was dilated 4 cm and 100% effaced, with fetal parts palpable at the external os. Abdominal ultrasound confirmed a viable cephalic gestation without fetal anomalies, no evidence of abruption, and a normal volume of amniotic fluid (AF). Amniocentesis findings were consistent with intra-amniotic infection. Labor induction and triple antibiotics were given. Despite 24 hours of oxytocin, followed by prostaglandin E2 vaginal suppositories, 20 mg every 4 hours 3 24 hours, there were no regular uterine contractions. Repeat ultrasound showed markedly decreased AF volume consistent with possible membrane rupture, a fundal placenta, and a fundal “mass” that was interpreted as a uterine contraction after partial placental separation. Prostaglandin E1 vaginal suppositories, 200 mcg every 6 hours 3 24 hours followed. With no labor, on hospital day 4, the previous ultrasounds were reviewed and believed to be compatible with an empty uterine fundus and, on sagittal imaging, anterior bulging of the cervicoisthmic region, consistent with cervical ectopic pregnancy. During laparotomy, the cervix was markedly distended, elongated, and extremely soft and friable. With the use of noncrushing Glassman intestinal clamps to develop pedicles, a hysterectomy was done with a 3000-mL estimated blood loss. On pathologic examination, the placenta was adherent to the upper cervix and lower uterine segment with an extensive accreta and acute chorioamnionitis. After resolution of an ileus, the woman was discharged on postoperative day 7.

Do Obese Women Need Higher Dosages of Misoprostol for Labor Induction? [6A]

INTRODUCTION: To determine the association between maternal BMI and time to delivery in women receiving misoprostol for labor induction (IOL). METHODS: This is a retrospective cohort study of women undergoing IOL with intravaginal misoprostol from 1/2013–2/2015. Women admitted for IOL with singleton, term, cephalic gestations were identified through a database. Maternal demographics, obstetrical variables, and admission BMIs were collected. Time to delivery (vaginal and cesarean) from the initial misoprostol dose was primary outcome. Groups were made based on maternal BMI and misoprostol dose (25 mcg vs 50 mcg). Time to delivery was compared among BMI categories stratified for misoprostol dose using two-sample t test, Wilcoxon rank sum test, and exact chi-square test. A P value less than 0.05 was considered significant. Kaplan Meyer survival and time to event curves were created. RESULTS: 483 patients were included. Mean gestational age was 39.2±1.6 wks, median parity was 0 (range 0–1), and maternal age was 30.5±6.1. Misoprostol 25 mcg was most commonly used (n=290, 60%). Vaginal delivery was achieved in 79% (n=382). More than 90% (n=435) of the women had BMIs greater than 30. Time to delivery was significantly longer with BMIs greater than 30 when misoprostol 25 mcg was used compared with 50 mcg. For BMIs greater than or equal to 40, time to delivery was six hours longer regardless of dose. CONCLUSION: There is an association between maternal BMI and initial misoprostol dosage on time to delivery. Admission BMI should be taken into consideration when dosing misoprostol for IOL.