The causes of stillbirths in south Asia: results from a prospective study in India and Pakistan (PURPOSe).

BACKGROUND: South Asia contributes more than a third of all global stillbirths, yet the causes remain largely unstudied in this region. New investigations, including novel assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of stillbirth. We sought to assess underlying and contributing causes of stillbirth from settings in India and Pakistan. METHODS: In this prospective cohort study (PURPOSe), we report the cause of death in stillbirths in hospitals in central India and south Pakistan (Davangere, India [three public and private hospitals] and Karachi, Pakistan [one public maternity and one children's hospital]). Women aged 15 years or older and with a known stillbirth (defined as a pregnancy at 20 or more weeks of gestation with the in-utero death of a fetus) weighing 1000 g or more were included in the study. Maternal clinical factors, placental evaluation, fetal tissue evaluation (from minimally invasive tissue sampling), and PCR for microbial pathogens were used to identify the causes of death. An expert panel reviewed available data for all stillbirths to identify the primary and contributing maternal, placental, and fetal causes of stillbirth. FINDINGS: Between Sept 1, 2018, and Feb 12, 2020, 981 stillborns were included and, of those, 611 were reviewed by the expert panel. The primary maternal causes of stillbirth were hypertensive disease in 221 (36%) of 611 stillbirths, followed by severe anaemia in 66 (11%) stillbirths. The primary placental causes were maternal and fetal vascular malperfusion, in 289 (47%) stillbirths. The primary fetal cause of stillbirth was intrauterine hypoxia, in 437 (72%) stillbirths. We assessed the overlap of main causes and 116 (19%) stillbirths had intrauterine hypoxia, placental malperfusion, and eclampsia or pre-eclampsia indicated as primary causes of death. Infection (including of the placenta, its membranes, and in the fetus) and congenital anomalies also were causative of stillbirth. INTERPRETATION: In south Asia, fetal asphyxia is the major cause of stillbirth. Several placental lesions, especially those associated with maternal and fetal vascular malperfusion and placental abruption, have an important role in asphyxia and fetal death. Maternal hypertension, and especially pre-eclampsia, is often the primary maternal condition associated with this pathway. FUNDING: Bill & Melinda Gates Foundation.

Effect of chronic administration of inhibin and testosterone on spermatogenesis in adult male rats.

Inhibin (Inh) and testosterone (T) were administered to adult male rats for 32 days to evaluate their effect on spermatogenesis. Fifty micrograms of Inh was injected subcutaneously twice daily, and T was administered as Silastic implants 2.5 cm in length. Weights of testes and epididymides were significantly decreased in (Inh + T)- and T-treated groups, but not in Inh-treated rats. Although Inh alone could suppress both the testicular and the epididymal sperm count, maximum suppression was observed in the (Inh + T)-treated group. The effect on the epididymal sperm count, however, was pronounced. The accessory organ weights remained unaffected in all treated groups. Chronic administration of Inh and T results in partial impairment of spermatogenesis.

Effect of FSH deprivation on spermatogenesis in prepubertal mice.

A specific antiserum to ovine follicle stimulating hormone (AS/FSH) raised in rabbits and administered to prepubertal mice from days 5 to 35 of age, inhibited intermediate and type B spermatogonia. Development of spermatocytes, spermatids, and spermatozoa was affected, indicating a role for FSH in the initiation of spermatogenesis. Decrease in the testicular and epididymal weights, but not that of seminal vesicles and ventral prostate, demonstrated the specific action of AS/FSH. Reduction in the weights of the epididymis in AS/FSH-injected mice accompanied by the absence of spermatozoa in the lumen suggests a possible role for FSH in spermiation.

Effect of inhibin on ovulation and implantation in mice.

Injection of antiserum to ovine FSH on the day of proestrus could inhibit ovulation in the next cycle. Inhibin preparation purified from sheep ovaries failed to affect ovulation in mice. Suppression of FSH by this preparation of inhibin during early pregnancy reversed the mitotic index. Administration of inhibin during the peri-implantation period terminated pregnancy in mice. The inhibin preparation decreases FSH in circulation which in turn may possibly reduce ovarian estrogens, thereby inhibiting pregnancy.