Bob Kronemyer

“Previous studies suggest that altered growth patterns in fetal life and infancy are related to increased risks of cardiovascular diseases in adulthood,” said leading investigator Romy Gonçalves, MSc, who is a PhD candidate in pediatric epidemiology at Erasmus MC, University Medical Center in Rotterdam, the Netherlands. “For example, low birth weight is associated with an unfavorable body composition, higher blood pressure, and higher levels of cholesterol and triglycerides.”

Carotid intima-media thickness and carotid distensibility can both be measured by ultrasound. “The intima-media thickness reflects the inner and middle layer of an artery, and plaque buildup can be identified this way,” Gonçalves told 

Arterial distensibility reflects the elasticity of an artery, according to Gonçalves. “Decreased distensibility is associated with increased risk of arterial wall damage,” she said. “In adults, suboptimal quality of the carotid artery, such as increased carotid intima-media thickness and reduced carotid distensibility, is related to the development of atherosclerosis and cardiovascular diseases. However, this relationship is less clear in children.”

The population-based prospective cohort study was conducted from early fetal life onward in 4,484 offspring (50.4% girls and 57.5% Dutch ethnicity) of women in Rotterdam, the Netherlands, delivering between April 2002 and January 2006.

Estimated fetal weight was measured in the second and third trimester, whereas infant weight was measured at 6, 12 and 24 months.

Follow-up measurements were available for the children at a median age of 9.7 years.

Gestational age at birth was not associated with markers of arterial health; however, a 500 g higher birth weight was linked to significantly increased carotid intima-media thickness and a lower carotid distensibility.

Compared to children with a birth weight of 2500 g to 4500 g, those weighing more than 4500 g had the lowest carotid distensibility.

In addition, compared to children with normal fetal and infant growth, children with normal fetal growth that was followed by accelerated infant growth had the highest carotid intima-media thickness.

The observed associations were mostly explained by childhood body mass index (BMI).

“We hypothesized that children born with low or high birth weight would have increased carotid intima-media thickness and lower carotid distensibility,” Gonçalves said. “But we did not find associations of low birth weight with arterial health.”

The relations of higher fetal weight and infant weight growth with arterial health outcomes are quite novel and indicate that very early-in-life increased weight gain has an effect on the carotid intima-media thickness and carotid distensibility, according to Gonçalves. “Our results suggest that high birth weight followed by higher infant and childhood weight gain is associated with an increased risk of adverse arterial health,” she said.

Gonçalves said further research is needed to examine the extent that adverse arterial health in childhood persists into adulthood. “Our outcomes imply that optimizing growth in early life might be beneficial for arterial health in later life,” she said. “Because our results were partly explained by childhood BMI, preventing high infant weight gain and childhood obesity could aid in reducing adverse arterial health.”

Exemplary prenatal care and information for caregivers and parents on reducing excessive infant weight gain could aid in reducing childhood obesity and subsequent cardiovascular diseases.

“I believe further studies should focus on longitudinal carotid measurements and determining if adverse childhood arterial health persists into adulthood,” Gonçalves said. “Thereby, it could be determined if measurements of childhood arterial health might add to prevention strategies to improve cardiovascular health later in life.”

This article was published by our sister publication Contemporary OB/GYN.

Gonçalves R, Wiertsema CJ, Silva CCV, et al. Associations of fetal and infant growth patterns with early markers of arterial health in school-aged children. 

. Published online June 29, 2022. doi:10.1001/jamanetworkopen.2022.19225

Articles

Both higher fetal and infant weight growth patterns are linked to early markers of impaired arterial health, according to a study published in JAMA Network Open.

Fetal/infant growth patterns and early markers of arterial health

“Women with epilepsy during pregnancy often worry that their disease or treatment will hurt their unborn child,” said principal investigator Marte-Helene Bjork, MD, PhD, a consultant neurologist at Haukeland University Hospital in Bergen, Norway. “These women require answers to which treatment is the least harmful. However, because there is a lack of safety data for newer antiseizure medication, I often could not give them evidence-based information.”

The Nordic register-based study of antiepileptic drugs in pregnancy is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden. Data from 1996 to 2017 was assessed.

Prenatal exposure to antiseizure medication was determined from maternal prescription fills between last menstrual period and birth for 4,494,926 alive-born children, of whom 51.3% were male.

The authors estimated the cumulative incidence of neurodevelopmental disorders at age 8 in exposed and unexposed children to antiseizure medications.

Among the 21,634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of autism spectrum disorder (ASD), and 0.8% had a diagnosis of intellectual disability (ID) by age 8.

This compared to a rate of 4.3% for ASD and 3.1% for ID in children who were exposed to topiramate monotherapy, and 2.7% and 2.4% respectively, for those exposed to valproate monotherapy.

The study also found that the duo-therapies levetiracetam with carbamazepine and lamotrigine with topiramate were linked to increased risks of neurodevelopmental disorders in children of women with epilepsy: an 8-year cumulative incidence of 5.7% and 7.5%, respectively. There was no increased risk for levetiracetam with lamotrigine.

“We were surprised by the strong associations between prenatal exposure to topiramate and neurodevelopmental disorders in the children,” Bjork told 

. “We knew that valproate was linked to these disorders; however, there were scant data on long-term effects of topiramate exposure.”

Even though there are some signals for increased risk of congenital malformations after exposure to topiramate, the investigators did not expect the associations between autism and ID to be almost as strong as for valproate.

“We were also surprised that the connections between specific duo-therapy combinations to neurodevelopmental disorders were so different, depending on which drugs were used in combination,” Bjork said. “I am personally relieved that the combination of levetiracetam and lamotrigine was not associated with increased risk of neurodevelopmental disorders because it is a combination used by many patients that I care for, when a single drug is not enough to stop their seizures.”

Bjork believes that women of childbearing age should not use topiramate, if other antiseizure medications are effective and tolerated. “If they need to use this drug, they should be very well informed and use safe contraception,” she said. “Also, if they need to use topiramate in pregnancy, the lowest effective dose should be used.”

Bjork, chair of the Bergen Epilepsy Group and an associate professor of clinical medicine at the University of Bergen, is deeply concerned that new antiseizure medications indicated for women in their childbearing years “are not routinely investigated for long-term and short-term safety. For instance, topiramate came on the marked in the 1990s, but we only now have this information. We should have a better system that does not leave investigations of pregnancy drug safety to single research groups or funders.”

Bjork also noted it is unfair that women of childbearing age have fewer treatment options than men for seizures.

Bjork receives advisory board honoraria personal fees from Eisai, consultancy and personal fees from Novartis Norway, and advisory board honoraria personal fees from Jazz Pharmaceuticals and Angelini Pharma.

Bjork M-H, Zoega H, Leinonen MK, et al. Association of prenatal exposure to antiseizure medication with risk of autism and intellectual disability. 

. Published online May 31, 2022. doi:10.1001/jamaneurol.2022.1269

Prenatal exposure to the antiseizure medications topiramate and valproate may cause a significantly increased risk of neurodevelopmental disorders in offspring, according to a cohort study in JAMA Neurology.

Prenatal exposure to antiseizure medication and fetal autism

“Although some antifungal drugs such as azoles have been applied clinically for many years, their therapeutic value is very limited due to the emergence of drug-resistant strains,” wrote the authors.

Previous studies have shown that the adhesion of 

) to vaginal epithelial cells is essential for the pathogenesis of vulvovaginal candidiasis (VVC).

 to vaginal epithelial cells might be an effective strategy to treat VVC.

Berberine, a quaternary ammonium compound, is the most prevalent bioactive component found in two traditional Chinese herbs: 

Applied clinically, berberine treats diseases like bacterial diarrhea and diabetes, plus can function as an antibacterial, antifungal, anti-inflammatory, immunomodulatory, and even as an anti-cancer agent.

The antifungal mechanism of berberine may entail the down-regulation of some key genes related to the integrity of the 

 cell wall after treatment with this compound, such as the hypha-specific gene ECE1 related to the morphological transformation of 

 and the genes FKS1 and FKS2 linked to the synthesis of beta-glucan components of 

 SC5314 was provided by the College of Pharmacy, Second Military Medical University in Shanghai, China. The glycerol-preserved fungal strain removed from the -80° C refrigerator was initially streaked onto Sabouraud’s agar.

Then, by using a single colony, the strain was routinely inoculated for three generations in Sabouraud’s agar plates. Afterward, the strain was activated and propagated in liquid Sabouraud medium at 37° C for 12 to 16 hours, until exponential growth phase was achieved.

 cells were pooled by centrifugation at 3,000 ×g. After two washing steps with sterile phosphate buffered saline (PBS), cells were resuspended in RPMI-1640 medium and adjusted to a defined cell density via a hemocytometer, prior to subsequent tests.

For cell culture, A431 human vaginal epidermoid carcinoma cell line was cultured at 37°C with 5% CO2 in Dulbecco’s Modified Eagle’s Medium, supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin.

At 24 hours prior to experimentation, the culture medium was replaced with serum-free medium and maintained until cell harvest.

Gram staining was used to observe the adherence of 

This study demonstrated that berberine significantly inhibited the adhesion of 

 to vaginal epithelial cells by reducing the expressions of intercellular adhesion molecule 1 (ICAM-1) and the proteins mucin 1 and mucin 4 in vaginal epithelial cells, which are vital in modulating the adhesion of 

 to host cells, according to the authors.

Berberine also balanced interleukin-2 (IL-2) and interleukin-4 (IL-4) expressions, which are instrumental in regulating the inflammatory response caused by 

“Hence, our findings demonstrate that berberine may be a potential therapeutic agent for VVC by interfering with the adhesion of 

 to vaginal epithelial cells and represents a new pathway for developing antifungal therapies agents from natural herbs,” wrote the authors.

Originally published on our sister brand, 

1. Zhao T, Zhang K, Shi G, et al. Berberine inhibits the adhesion of 

. Published online February 28, 2022. doi:10.3389/fphar.2022.814883

2. Martin H., Govern MM, Abbey L. et al. Inhibition of adherence of the yeast 

 to buccal epithelial cells by synthetic aromatic glycoconjugates. 

Vaginal yeast infections were successfully treated with berberine, a biologically active herbal alkaloid, according to a study published in Frontiers in Pharmacology.

Berberine promising therapy to treat vulvovaginal candidiasis

A higher childhood body mass index (BMI) was linked to a significantly greater risk of premenstrual disorders (PMDs) and premenstrual symptoms in young adulthood compared to children with normal BMI, according to a prospective cohort study in JAMA Network Open.

The study also concluded that individuals with high BMI throughout adolescence reported significantly greater premenstrual symptoms in adulthood compared to those who maintained normal BMI throughout adolescence.

“A few previous studies have shown that adulthood adiposity is positively associated with PMDs,” said first author Donghao Lu, MD, PhD, an assistant professor of epidemiology at Karolinska Institutet in Stockholm, Sweden. “However, in our 2021 study in the journal 

 we found that in the cohort from the Growing Up Today Study (GUTS), 70% of individuals with PMDs had first symptom onset in adolescence, suggesting that early life factors may contribute importantly to the etiology.”

 that such an association could be attributable to obesity present already in childhood. “But there was no data on the relationship between childhood BMI and risk of PMDs,” he said.

The study comprised 6,524 US female participants from GUTS and was conducted from 1996 to 2013. The mean age of subjects was 26 years, of whom 93.6% were White and 15.4% met the criteria for a PMD.

BMI was estimated via self-reported height and weight through adolescence and converted to BMI for age. Premenstrual symptoms and identified PMDs were determined with a validated scale based on the Calendar of Premenstrual Experiences.

An increase of standard deviation of BMI reported at a mean age of 12.7 years was connected to a 9% increased risk of PMDs.

Associations were particularly pronounced for premenstrual dysphoric disorder and for PMDs with symptom onset prior to age 20 and remained in the absence of psychiatric comorbidities, including depression, anxiety, and disordered eating behaviors.

In addition, individuals with a high BMI throughout adolescence had a higher burden of premenstrual symptoms versus those with normal BMI throughout adolescence.

However, females with a high BMI early in adolescence, followed by a mild decrease thereafter, did not report a higher incidence of premenstrual symptoms.

“These findings are in line with our hypothesis,” Lu said. “Interestingly, our data showed that BMI from the age of 11 to 18 was positively associated with severity of premenstrual symptoms. In contrast, null associations were noted for body shape in early childhood—5 years of age—or middle-childhood BMI—9 and 10 years of age.”

Unfortunately, the awareness of PMDs among health professionals and the public is low. “There has been some improvement in recent years,” Lu said. “Health care providers should be aware of the risk of PMDs in children with greater body mass and educate girls and their parents about premenstrual symptoms.”

Future research is also needed to clarify further how specific ages at exposure relate to risk, according to Lu.

1. Lu D, Aleknaviciute J, Kamperman AM, et al. Association between childhood body size and premenstrual disorders in young adulthood. 

. Published online March 8, 2022. doi:10.1001/jamanetworkopen.2022.1256

2. Lu D, Aleknaviciute J, Bjarnason R, Tamimi RM, et al. Pubertal development and risk of premenstrual disorders in young adulthood. 

A  prospective cohort study examines whether higher childhood body mass index (BMI) was linked to a greater risk of premenstrual symptoms in young adulthood compared than children with lower BMIs.

Higher risk of premenstrual disorders is seen with higher BMI in childhood

A previous study by the authors published in the

 Journal of Maternal-Fetal & Neonatal Medicine

 in 2020 found that roughly 25% of women with severe maternal morbidity also had preterm birth.

“In that paper, we saw some differences in risk for dual burden by insurance type and wanted to explore those findings more thoroughly,” said Alison El Ayadi, ScD, MPH, an associate professor of ob-gyn and reproductive sciences at the University of California, San Francisco, who was a co-author of both studies.

The current study estimated relative risks of dual burden by maternal sociodemographic and perinatal characteristics in the 2007 to 2012 California birth cohort dataset, stratified by insurance type and comparing effects across insurance categories.

Dual burden ranged from 0.36% of privately insured births to 0.41% of uninsured births.

Obstetric comorbidities, multiple gestation, parity and birth mode were linked to the largest risks across all insurance types, but the effect magnitude differed.

The adjusted relative risk (aRR) of dual burden associated with preeclampsia superimposed on preexisting hypertension spanned from 9.1 for the privately insured to 15.9 for the uninsured.

In contrast, the aRR of dual burden associated with cesarean birth for primiparas ranged from 3.1 with Medi-Cal to 5.4 with other insurance, and for multiparas from 7.0 to 19.4, respectively.

“We expected that obstetric comorbidities, parity and mode of birth would have the largest impact on uninsured women, followed by women with Medi-Cal, compared to those with private insurance,” El Ayadi told 

But the investigators were surprised to find that uninsured women were the only group without an advanced maternal age-related increase in dual burden.

The authors are uncertain why the risk of dual burden connected to multiple gestation for uninsured women was lower compared to other insurance categories. “We know, though, that access to assisted reproductive technology (ART) is associated with type of insurance coverage and with multiple births,” El Ayadi said. “These inter-relationships may play a role in our findings.”

The study also found no significant Black-White disparity in dual burden risk among uninsured women. “As health disparities by race/ethnicity reflect the impact of exposure to chronic stress from racism, and health insurance is another rough proxy measure for socioeconomic status, it is possible that this finding reflects the greater level of disadvantage among the uninsured population overall,” El Ayadi said.

The variances that the study found in the effect size for the sociodemographic and pregnancy-related risk factors by insurance type “suggest that important differences in care quality exist by insurance payor,” El Ayadi said.

Moreover, the study indicates that in order to improve maternal and neonatal health, it is paramount that all birthing mothers and infants receive high-quality peripartum care and support, regardless of insurance payor.

“The improvements in maternal outcomes that are now being demonstrated with Medicaid expansion are a great policy example of how structural change can have an impact,” El Ayadi said.

Despite such progress, it is challenging to disentangle the relationship between type of insurance at the individual level and clinic or hospital quality because many entities serve populations with either mostly private or mostly public coverage.

“Future studies should aim to determine the extent to which these types of differences are related to coverage policies of insurers versus inadequate resources for hospitals serving more disadvantaged populations,” El Ayadi said.

This article was originally published by sister publication Contemporary OB/GYN.

Lyndon A, Bear R, Gay CL, et al. A population-based study to identify the prevalence and correlates of the dual burden of severe maternal morbidity and preterm birth in California. 

. 2021 Apr;34(8):1198-1206. doi:10.1080/14767058.2019.1628941

El Ayadi AM, Baer RJ, Gay C, et al. Risk factors for dual burden of severe maternal morbidity and preterm birth by insurance type in California. 

. Published online January 18, 2022. doi:10.1007/s10995-021-03313-1

Risk factors for the dual burden of severe maternal morbidity and preterm birth differ significantly by insurance type across sociodemographic and perinatal considerations in the state of California.

Insurance type plays role in impact of preterm birth and maternal morbidity

Sex is a natural part of human development and ensuring that young people are getting quality sex education is crucial,” said principal investigator Laura Lindberg, PhD, a principal research scientist at the Guttmacher Institute, a New York City research and policy organization pursuing sexual and reproductive health and rights.

The study culled nationally representative data from the National Survey of Family Growth, in youth aged 15 to 19 years, for 2 time periods: 2011 to 2015 and 2015 to 2019.

Between the 2 time periods, there were only a few significant changes in adolescents’ receipt of formal sex education.

Instruction on waiting until marriage to have sex declined from 73% to 67% among females (

In addition, in both time periods, only about half of adolescents received sex education that meets the federal minimum standard.

In the later time period, there were significant gender differences in the instruction to wait until marriage to have sex: 67% of females received instruction vs 58% of males (

Condom skills were taught to 55% of females and 60% of males (

However, non-Hispanic Black and Hispanic males were significantly less likely than non-Hispanic White males to receive formal instruction before the first sex on sexually transmitted infection/HIV, birth control or where to get birth control in the later time period.

Data from the later time period also found that many adolescents reported religious settings as the sources of instruction about waiting until marriage to have sex: 56% of females and 49% of males. But nearly none received instruction about birth control from such settings.

“Evidence shows that adolescents in the United States are clearly not getting the quality sex education they need,” Lindberg told 

. “In fact, it is shocking that our research shows that young people are less likely to receive information about birth control now than they were 25 years ago.”

Moreover, there are concerning inequities between who has access to sex education by race, gender, and sexual orientation that leaves young people vulnerable, according to Lindberg. “For example, queer young men are significantly less likely than their straight counterparts to receive information on essential sex ed topics,” she said.

Withholding critical information about sexual health violates adolescents’ right to accurate, timely information, says Lindberg, who noted that health care providers can and must help address this gap by furnishing teens with the information and services they need for their health and wellbeing.

“Our schools and communities also need to expand their provision of sex education, with support from federal, state, and local policies,” Lindberg said. “Policymakers should create links to sexual health services for young people who face the greatest barriers to care.”

To begin, Lindberg urges policymakers to fully fund the Teen Pregnancy Prevention Program and Personal Responsibility Education Program. “These are federally funded grant programs that support evidence-based, medically accurate programs to reduce adolescent pregnancy and STIs,” she said.

Lindberg also advocates passage of the Real Education and Access for Healthy Youth Act, “which would eliminate funding for abstinence-only programs and establish the country’s first federal grant program for comprehensive sex education,” she said.

Furthermore, Lindberg would like the federal government to eliminate all funding for 

misleading and incomplete abstinence-only-until-marriage programs

, “which harm young people. Instead, this money should be used to fund sex education programs that offer informative and inclusive curricula.”

Lindberg LD, Kantor LM. Adolescents’ receipt of sex education in a nationally representative sample, 2011 – 2019. 

. Published online November 4, 2021. doi:org/10.1016/j.jadohealth.2021.08.027

Many adolescents across the United States lack quality sex education, a trend that has worsened in recent years. Moreover, national statistics mask significant inequities in the receipt of formal sex education by gender, race and ethnicity, sexual orientation, and the location of instruction.